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Evotourism ®

A Smithsonian magazine special report

AT THE SMITHSONIAN

Seven new things we learned about human evolution in 2021.

Paleoanthropologists Briana Pobiner and Ryan McRae reveal some of the year’s best findings in human origins studies

Briana Pobiner and Ryan McRae

This year—2021—has been a year of progress in overcoming the effects of the Covid-19 pandemic on human evolution research. With some research projects around the world back up and running, we wanted to highlight new and exciting discoveries from 13 different countries on five different continents. Human evolution is the study of what links us all together, and we hope you enjoy these stories we picked to show the geographic and cultural diversity of human evolution research, as well as the different types of evidence for human evolution, including fossils, archaeology, genetics, and even footprints!

New Paranthropus robustus fossils from South Africa show microevolution within a single species.

The human fossil record, like any fossil record, is full of gaps and incomplete specimens that make our understanding of complex evolutionary trends difficult. Identifying species and the process by which new species emerge from fossils falls in the realm of macroevolution , or evolution over broad time scales. These trends and changes tend to be more pronounced and easier to identify in the fossil record; think about how different a Tyrannosaurus rex and a saber-toothed cat are from each other. Human evolution only took place over the course of 5 to 8 million years, a much shorter span compared to the roughly 200 million years since dinosaurs and mammals shared a common ancestor. Because of this, smaller-scale evolutionary changes within a single species or lineage over time, called microevolution , is often difficult to detect.

Fossils of one early human species, Paranthropus robustus , are known from multiple cave sites in South Africa. Like other Paranthropus species, P. robustus is defined by large, broad cheeks, massive molars and premolars, and a skull highly adapted for intense chewing. Fossils of P. robustus from Swartkrans cave, just 20 miles west of Johannesburg, are dated to around 1.8 million years ago and show a distinct sagittal crest, or ridge of bone along the top of the skull, with their jaws indicating a more efficient bite force. Newly discovered fossils of P. robustus from Drimolen cave , about 25 miles north of Johannesburg, described by Jesse Martin from La Trobe University and colleagues in January, are at least 200,000 years older (2.04-1.95 million years old) and have a differently positioned sagittal crest and a less efficient bite force, among other small differences. Despite numerous disparities between fossils at the two sites, they much more closely resemble each other than any other known species of hominin. Because of this, researchers kept them as the same species from two different time points in a single lineage . The differences between fossils at the two sites highlight microevolution within this Paranthropus lineage .

Fossil children from Kenya, France, and South Africa tell us how ancient and modern human burial practices changed over time.

Most of the human fossil record includes the remains of adult individuals; that’s likely because larger and thicker adult bones, and bones of larger individuals, are more likely to survive the burial, fossilization, and discovery processes. The fossil record also gets much richer after the practice of intentional human burial began, starting at least 100,000 years ago .

In November, María Martinón-Torres from CENIEH (National Research Center on Human Evolution) in Spain, Nicole Boivin and Michael Petraglia from the Max Planck Institute for the Science of Human History in Germany, and other colleagues announced the oldest known human burial in Africa —a two-and-a-half to three-year-old child from the site of Panga ya Saidi in Kenya. The child, nicknamed “Mtoto” which means “child" in Kiswahili, was deliberately buried in a tightly flexed position about 78,000 years ago, according to luminescence dating. The way the child’s head was positioned indicates possible burial with a perishable support, like a pillow. In December, a team led by University of Colorado, Denver’s Jaime Hodgkins reported the oldest known burial of a female modern human infant in Europe . She was buried in Arma Veirana Cave in Italy 10,000 years ago with an eagle-owl talon, four shell pendants, and more than 60 shell beads with patterns of wear indicating that adults had clearly worn them for a long time beforehand. This evidence indicates her treatment as a full person by the Mesolithic hunter-gatherer group she belonged to. After extracted DNA determined that she was a girl, the team nicknamed her “Neve” which means “snow” in Italian. Aside from our own species, Neanderthals are also known to sometimes purposefully bury their dead . In December, a team led by Antoine Balzeau from the CNRS (the French National Centre for Scientific Research) and Muséum National d’Histoire Naturelle in France and Asier Gómez-Olivencia from the University of the Basque Country in Spain provided both new and re-studied information on the archaeological context of the La Ferrassie 8 Neanderthal skeleton, a two-year-old buried in France about 41,000 years ago. They conclude that this child, who is one of the most recently directly dated Neanderthals (by Carbon-14) and whose partial skeleton was originally excavated in 1970 and 1973, was purposefully buried . There have also been suggestions that a third species, Homo naledi , known from South Africa between about 335,000 and 236,000 years ago, purposefully buried their dead—though without any ritual context. In November, a team led by University of the Witwatersrand’s Lee Berger published two papers with details of skull and tooth fragments of a four to six-year-old Homo naledi child fossil , nicknamed “Leti” after the Setswana word “letimela” meaning “the lost one.” Given the location of the child’s skull found in a very narrow, remote and inaccessible part of the Rising Star cave system, about a half mile from Swartkrans, this first partial skull of a child of Homo naledi yet recovered might support the idea that this species also deliberately disposed of their dead.

The first Europeans had recent Neanderthal relatives, according to genetic evidence from Czechia and Bulgaria.

Modern humans, Homo sapiens , evolved in Africa and eventually made it to every corner of the world. That is not news. However, we are still understanding how and when the earliest human migrations occurred. We also know that our ancestors interacted with other species of humans at the time, including Neanderthals , based on genetic evidence of Neanderthal DNA in modern humans alive today—an average of 1.9 percent in Europeans.

Remains of some of the earliest humans in Europe were described this year by multiple teams, except they were not fully human. All three of the earliest Homo sapiens in Europe exhibit evidence of Neanderthal interbreeding (admixture) in their recent genealogical past. In April, Kay Prüfer and a team from the Max Planck Institute for the Science of Human History described a human skull from Zlatý kůň, Czechia, dating to around 45,000 years old . This skull contains roughly 3.2 percent Neanderthal DNA in the highly variable regions of the genome, comparable with other humans from around that time. Interestingly, some of these regions indicating Neanderthal admixture were not the same as modern humans, and this individual is not directly ancestral to any population of modern humans, meaning they belonged to a population that has no living descendants. Also in April, Mateja Hajdinjak and a team from the Max Planck Institute for Evolutionary Anthropology described three similar genomes from individuals found in Bacho Kiro Cave, Bulgaria, dating between 46,000 and 42,000 years old . These individuals carry 3.8, 3.4, and 3.0 percent Neanderthal DNA, more than the modern human average. Based on the distribution of these sequences, the team concluded that the three individuals each had a Neanderthal ancestor only six or seven generations back. This is roughly the equivalent length of time from the turn of the twentieth century to today. Interestingly, these three genomes represent two distinct populations of humans that occupied the Bulgarian cave—one of which is directly ancestral to east Asian populations and Indigenous Americans, the other of which is directly ancestral to later western Europeans. These findings suggest that there is continuity of human occupation of Eurasia from the earliest known individuals to present day and that mixing with Neanderthals was likely common, even among different Homo sapiens populations.

A warty pig from Indonesia, a kangaroo from Australia, and a conch shell instrument from France all represent different forms of ancient art.

Currently, the world’s oldest representational or figurative art is a cave painting of a Sulawesi warty pig found in Leang Tedongnge, Indonesia, that was dated to at least 45,500 years ago using Uranium series dating—and reported in January by a team led by Adam Brumm and Maxime Aubert from Griffith University. In February, a team led by Damien Finch from the University of Melbourne in Australia worked with the Balanggarra Aboriginal Corporation, which represents the Traditional Owners of the land in the Kimberly region of Australia, to radiocarbon date mud wasp nests from rock shelters in this area. While there is fossil evidence of modern humans in Australia dating back to at least 50,000 years ago , this team determined that the oldest known Australian Aboriginal figurative rock paintings date back to between around 17,000 and 13,000 years ago . The naturalistic rock paintings mainly depict animals and some plants; the oldest example is of a about 6.5 footlong kangaroo painting on the ceiling of a rock shelter dated to around 17,300 years ago. Right around that time, about 18,000 years ago, an ancient human in France cut off the top of a conch shell and trimmed its jagged outer lip smooth so it could be used as the world’s oldest wind instrument . A team led by Carole Fritz and Gilles Tostello from the Université de Toulouse in France reported in February that they re-examined this shell, discovered in Marsoulas Cave in 1931, using CT scanning. In addition to the modifications described above, they found red fingerprint-sized and shaped dots on the internal surface of the shell, made with ochre pigment also used to create art on the walls of the cave. They also found traces of a wax or resin around the broken opening, which they interpreted as traces of an adhesive used to attach a mouthpiece as found in other conch shell instruments.

Fossil finds from China and Israel complicate the landscape of human diversity in the late Pleistocene.

This year a new species was named from fossil material found in northeast China: Homo longi . A team from Hebei University in China including Qiang Ji, Xijun Ni, Qingfeng Shao and colleagues described this new species dating to at least 146,000 years old. The story behind the discovery of this cranium is fascinating! It was hidden in a well from the Japanese occupying forces in the town of Harbin for 80 years and only recently rediscovered. Due to this history, the dating and provenience of the cranium are difficult to ascertain, but the morphology suggests a mosaic of primitive-like features as seen in Homo heidelbergensis , and other more derived features as seen in Homo sapiens and Neanderthals . Although the cranium closely resembles some other east Asian finds such as the Dali cranium , the team named a new species based on the unique suite of features. This newly named species may represent a distinct new lineage, or may potentially be the first cranial evidence of an enigmatic group of recent human relatives—the Denisovans . Adding to the increasingly complex picture of late Pleistocene Homo are finds from Nesher Ramla in Israel dating to 120,000 to 130,000 years old , described in June by Tel Aviv University’s Israel Hershkovitz and colleagues. Like the Homo longi cranium, the parietal bone, mandible and teeth recovered from Nesher Ramla exhibit a mix of primitive and derived features. The parietal and mandible have stronger affiliations with archaic Homo , such as Homo erectus , while all three parts have features linking them to Neanderthals. Declining to name a new species , the team instead suggests that these finds may represent a link between earlier fossils with “Neanderthal-like features” from Qesem Cave and other sites around 400,000 years ago to later occupation by full Neanderthals closer to 70,000 years ago. Regardless of what these finds may come to represent in the form of new species, they tell us that modern-like traits did not evolve simultaneously, and that the landscape of human interaction in the late Pleistocene was more complex than we realize.

The ghosts of modern humans past were found in DNA in dirt from Denisova Cave in Russia.

Denisova Cave in Russia, which has yielded fossil evidence of Denisovans and Neanderthals (and even remains of a 13-year-old girl who was a hybrid with a Neanderthal mother and Denisovan father), is a paleoanthropological gift that keeps on giving! In June, a team led by Elena Zavala and Matthias Meyer from the Max Planck Institute for Evolutionary Anthropology in Germany and Zenobia Jacobs and Richard Roberts from the University of Wollongong in Australia analyzed DNA from 728 sediment samples from Denisova Cave —the largest analysis ever of sediment DNA from a single excavation site. They found ancient DNA from Denisovans and Neanderthals… and modern humans, whose fossils have not been found there, but who were suspected to have lived there based on Upper Paleolithic jewelry typically made by ancient modern humans found in 45,000-year-old layers there. The study also provided more details about the timing and environmental conditions of occupation of the cave by these three hominin species: first Denisovans were there, between 250,000 and 170,000 years ago; then Neanderthals arrived at the end of this time period (during a colder period) and joined the Denisovans, except between 130,000 and 100,000 years ago (during a warmer period) when only Neanderthal DNA was detected. The Denisovans who came back to the cave after 100,000 years ago have different mitochondrial DNA, suggesting they were from a different population. Finally, modern humans arrived at Denisova Cave by 45,000 years ago. Both fossil and genetic evidence point to a landscape of multiple interacting human species in the late Pleistocene, and it seems like Denisova Cave was the place to be!

Fossilized footprints bring to light new interpretations of behavior and migration in Tanzania, the United States and Spain.

Usually when we think of fossils, we think of the mineralized remnants of bone that represent the skeletons of long since passed organisms. Yet trace fossils, such as fossilized footprints, give us direct evidence of organisms at a specific place in a specific time. The Laetoli footprints , for example, represent the earliest undoubted bipedal hominin, Australopithecus afarensis (Lucy’s species) at 3.6 million years ago. In December, a team led by Ellison McNutt from Ohio University announced that their reanalysis of some of the footprints from Site A at Laetoli were not left by a bear, as had been hypothesized, but by a bipedal hominin. Furthermore, because they are so different from the well-known footprints from Site G, they represent a different bipedal species walking within 1 kilometer (0.6 miles) of each other within the span of a few days! Recently uncovered and dated footprints in White Sands National Park , New Mexico, described in September by a team led by Matthew Bennett of Bournemouth University, place modern humans in the area between 23,000 to 21,000 years ago. Hypotheses as to how Indigenous Americans migrated into North America vary in terms of method (ice-free land corridor versus coastal route) as well as timing. Regardless of the means by which people traveled to North America, migration was highly unlikely, if not impossible, during the last glacial maximum (LGM), roughly 26,000 to 20,000 years ago. These footprints place modern humans south of the ice sheet during this period, meaning that they most likely migrated prior to the LGM . This significantly expands the duration of human occupation past the 13,000 years ago supported by Clovis culture and the roughly 20,000 years ago supported by other evidence. Furthermore, it means that humans and megafauna, like giant ground sloths and wooly mammoths, coexisted for longer than previously thought, potentially lending credit to the theory that their extinction was not caused by humans. Also interesting is that most of these footprints were likely made by children and teenagers, potentially pointing to division of labor within a community. Speaking of footprints left by ancient children, a team led by Eduardo Mayoral from Universidad de Huelva reported 87 Neanderthal footprints from the seaside site of Matalascañas in southwestern Spain in March. Dated at about 106,000 years ago, these are now the oldest Neanderthal footprints in Europe, and possibly in the world. The researchers conclude that of the 36 Neanderthals that left these footprints, 11 were children; the group may have been hunting for birds and small animals, fishing, searching for shellfish… or just frolicking on the seashore. Aw.

A version of this article  was originally published  on the PLOS SciComm blog.

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Briana Pobiner | READ MORE

Briana Pobiner is a paleoanthropologist with the National Museum of Natural History’s Human Origins Program . She lead's the program's education and outreach efforts. 

Ryan McRae | READ MORE

Dr. Ryan McRae is a paleoanthropologist studying the hominin fossil record on a macroscopic scale. He currently works for the National Museum of Natural History’s Human Origins Program as a contractor focusing on research, education, and outreach, and is an adjunct assistant professor of anatomy at the George Washington University School of Medicine and Health Sciences.

Introductory essay

Written by the educator who created What Makes Us Human?, a brief look at the key facts, tough questions and big ideas in his field. Begin this TED Study with a fascinating read that gives context and clarity to the material.

As a biological anthropologist, I never liked drawing sharp distinctions between human and non-human. Such boundaries make little evolutionary sense, as they ignore or grossly underestimate what we humans have in common with our ancestors and other primates. What's more, it's impossible to make sharp distinctions between human and non-human in the paleoanthropological record. Even with a time machine, we couldn't go back to identify one generation of humans and say that the previous generation contained none: one's biological parents, by definition, must be in the same species as their offspring. This notion of continuity is inherent to most evolutionary perspectives and it's reflected in the similarities (homologies) shared among very different species. As a result, I've always been more interested in what makes us similar to, not different from, non-humans.

Evolutionary research has clearly revealed that we share great biological continuity with others in the animal kingdom. Yet humans are truly unique in ways that have not only shaped our own evolution, but have altered the entire planet. Despite great continuity and similarity with our fellow primates, our biocultural evolution has produced significant, profound discontinuities in how we interact with each other and in our environment, where no precedent exists in other animals. Although we share similar underlying evolved traits with other species, we also display uses of those traits that are so novel and extraordinary that they often make us forget about our commonalities. Preparing a twig to fish for termites may seem comparable to preparing a stone to produce a sharp flake—but landing on the moon and being able to return to tell the story is truly out of this non-human world.

Humans are the sole hominin species in existence today. Thus, it's easier than it would have been in the ancient past to distinguish ourselves from our closest living relatives in the animal kingdom. Primatologists such as Jane Goodall and Frans de Waal, however, continue to clarify why the lines dividing human from non-human aren't as distinct as we might think. Goodall's classic observations of chimpanzee behaviors like tool use, warfare and even cannibalism demolished once-cherished views of what separates us from other primates. de Waal has done exceptional work illustrating some continuity in reciprocity and fairness, and in empathy and compassion, with other species. With evolution, it seems, we are always standing on the shoulders of others, our common ancestors.

Primatology—the study of living primates—is only one of several approaches that biological anthropologists use to understand what makes us human. Two others, paleoanthropology (which studies human origins through the fossil record) and molecular anthropology (which studies human origins through genetic analysis), also yield some surprising insights about our hominin relatives. For example, Zeresenay Alemsegad's painstaking field work and analysis of Selam, a 3.3 million-year old fossil of a 3-year-old australopithecine infant from Ethiopia, exemplifies how paleoanthropologists can blur boundaries between living humans and apes.

Selam, if alive today, would not be confused with a three-year-old human—but neither would we mistake her for a living ape. Selam's chimpanzee-like hyoid bone suggests a more ape-like form of vocal communication, rather than human language capability. Overall, she would look chimp-like in many respects—until she walked past you on two feet. In addition, based on Selam's brain development, Alemseged theorizes that Selam and her contemporaries experienced a human-like extended childhood with a complex social organization.

Fast-forward to the time when Neanderthals lived, about 130,000 – 30,000 years ago, and most paleoanthropologists would agree that language capacity among the Neanderthals was far more human-like than ape-like; in the Neanderthal fossil record, hyoids and other possible evidence of language can be found. Moreover, paleogeneticist Svante Pääbo's groundbreaking research in molecular anthropology strongly suggests that Neanderthals interbred with modern humans. Paabo's work informs our genetic understanding of relationships to ancient hominins in ways that one could hardly imagine not long ago—by extracting and comparing DNA from fossils comprised largely of rock in the shape of bones and teeth—and emphasizes the great biological continuity we see, not only within our own species, but with other hominins sometimes classified as different species.

Though genetics has made truly astounding and vital contributions toward biological anthropology by this work, it's important to acknowledge the equally pivotal role paleoanthropology continues to play in its tandem effort to flesh out humanity's roots. Paleoanthropologists like Alemsegad draw on every available source of information to both physically reconstruct hominin bodies and, perhaps more importantly, develop our understanding of how they may have lived, communicated, sustained themselves, and interacted with their environment and with each other. The work of Pääbo and others in his field offers powerful affirmations of paleoanthropological studies that have long investigated the contributions of Neanderthals and other hominins to the lineage of modern humans. Importantly, without paleoanthropology, the continued discovery and recovery of fossil specimens to later undergo genetic analysis would be greatly diminished.

Molecular anthropology and paleoanthropology, though often at odds with each other in the past regarding modern human evolution, now seem to be working together to chip away at theories that portray Neanderthals as inferior offshoots of humanity. Molecular anthropologists and paleoanthropologists also concur that that human evolution did not occur in ladder-like form, with one species leading to the next. Instead, the fossil evidence clearly reveals an evolutionary bush, with numerous hominin species existing at the same time and interacting through migration, some leading to modern humans and others going extinct.

Molecular anthropologist Spencer Wells uses DNA analysis to understand how our biological diversity correlates with ancient migration patterns from Africa into other continents. The study of our genetic evolution reveals that as humans migrated from Africa to all continents of the globe, they developed biological and cultural adaptations that allowed for survival in a variety of new environments. One example is skin color. Biological anthropologist Nina Jablonski uses satellite data to investigate the evolution of skin color, an aspect of human biological variation carrying tremendous social consequences. Jablonski underscores the importance of trying to understand skin color as a single trait affected by natural selection with its own evolutionary history and pressures, not as a tool to grouping humans into artificial races.

For Pääbo, Wells, Jablonski and others, technology affords the chance to investigate our origins in exciting new ways, adding pieces into the human puzzle at a record pace. At the same time, our technologies may well be changing who we are as a species and propelling us into an era of "neo-evolution."

Increasingly over time, human adaptations have been less related to predators, resources, or natural disasters, and more related to environmental and social pressures produced by other humans. Indeed, biological anthropologists have no choice but to consider the cultural components related to human evolutionary changes over time. Hominins have been constructing their own niches for a very long time, and when we make significant changes (such as agricultural subsistence), we must adapt to those changes. Classic examples of this include increases in sickle-cell anemia in new malarial environments, and greater lactose tolerance in regions with a long history of dairy farming.

Today we can, in some ways, evolve ourselves. We can enact biological change through genetic engineering, which operates at an astonishing pace in comparison to natural selection. Medical ethicist Harvey Fineberg calls this "neo-evolution". Fineberg goes beyond asking who we are as a species, to ask who we want to become and what genes we want our offspring to inherit. Depending on one's point of view, the future he envisions is both tantalizing and frightening: to some, it shows the promise of science to eradicate genetic abnormalities, while for others it raises the specter of eugenics. It's also worth remembering that while we may have the potential to influence certain genetic predispositions, changes in genotypes do not guarantee the desired results. Environmental and social pressures like pollution, nutrition or discrimination can trigger "epigenetic" changes which can turn genes on or off, or make them less or more active. This is important to factor in as we consider possible medical benefits from efforts in self-directed evolution. We must also ask: In an era of human-engineered, rapid-rate neo-evolution, who decides what the new human blueprints should be?

Technology figures in our evolutionary future in other ways as well. According to anthropologist Amber Case, many of our modern technologies are changing us into cyborgs: our smart phones, tablets and other tools are "exogenous components" that afford us astonishing and unsettling capabilities. They allow us to travel instantly through time and space and to create second, "digital selves" that represent our "analog selves" and interact with others in virtual environments. This has psychological implications for our analog selves that worry Case: a loss of mental reflection, the "ambient intimacy" of knowing that we can connect to anyone we want to at any time, and the "panic architecture" of managing endless information across multiple devices in virtual and real-world environments.

Despite her concerns, Case believes that our technological future is essentially positive. She suggests that at a fundamental level, much of this technology is focused on the basic concerns all humans share: who am I, where and how do I fit in, what do others think of me, who can I trust, who should I fear? Indeed, I would argue that we've evolved to be obsessed with what other humans are thinking—to be mind-readers in a sense—in a way that most would agree is uniquely human. For even though a baboon can assess those baboons it fears and those it can dominate, it cannot say something to a second baboon about a third baboon in order to trick that baboon into telling a fourth baboon to gang up on a fifth baboon. I think Facebook is a brilliant example of tapping into our evolved human psychology. We can have friends we've never met and let them know who we think we are—while we hope they like us and we try to assess what they're actually thinking and if they can be trusted. It's as if technology has provided an online supply of an addictive drug for a social mind evolved to crave that specific stimulant!

Yet our heightened concern for fairness in reciprocal relationships, in combination with our elevated sense of empathy and compassion, have led to something far greater than online chats: humanism itself. As Jane Goodall notes, chimps and baboons cannot rally together to save themselves from extinction; instead, they must rely on what she references as the "indomitable human spirit" to lessen harm done to the planet and all the living things that share it. As Goodall and other TED speakers in this course ask: will we use our highly evolved capabilities to secure a better future for ourselves and other species?

I hope those reading this essay, watching the TED Talks, and further exploring evolutionary perspectives on what makes us human, will view the continuities and discontinuities of our species as cause for celebration and less discrimination. Our social dependency and our prosocial need to identify ourselves, our friends, and our foes make us human. As a species, we clearly have major relationship problems, ranging from personal to global scales. Yet whenever we expand our levels of compassion and understanding, whenever we increase our feelings of empathy across cultural and even species boundaries, we benefit individually and as a species.

Get started

Zeresenay Alemseged

The search for humanity's roots, relevant talks.

Spencer Wells

A family tree for humanity.

Svante Pääbo

Dna clues to our inner neanderthal.

Nina Jablonski

Skin color is an illusion.

We are all cyborgs now

Harvey Fineberg

Are we ready for neo-evolution.

Frans de Waal

Moral behavior in animals.

Jane Goodall

What separates us from chimpanzees.

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• Review Article
• Published: 06 January 2021

The influence of evolutionary history on human health and disease

• Mary Lauren Benton   ORCID: orcid.org/0000-0002-5485-1041 1 , 2 ,
• Abin Abraham 3 , 4 ,
• Abigail L. LaBella   ORCID: orcid.org/0000-0003-0068-6703 5 ,
• Patrick Abbot 5 ,
• Antonis Rokas   ORCID: orcid.org/0000-0002-7248-6551 1 , 3 , 5 &
• John A. Capra   ORCID: orcid.org/0000-0001-9743-1795 1 , 5 , 6  

Nature Reviews Genetics volume  22 ,  pages 269–283 ( 2021 ) Cite this article

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• Evolutionary genetics
• Genetic variation
• Medical genetics

Nearly all genetic variants that influence disease risk have human-specific origins; however, the systems they influence have ancient roots that often trace back to evolutionary events long before the origin of humans. Here, we review how advances in our understanding of the genetic architectures of diseases, recent human evolution and deep evolutionary history can help explain how and why humans in modern environments become ill. Human populations exhibit differences in the prevalence of many common and rare genetic diseases. These differences are largely the result of the diverse environmental, cultural, demographic and genetic histories of modern human populations. Synthesizing our growing knowledge of evolutionary history with genetic medicine, while accounting for environmental and social factors, will help to achieve the promise of personalized genomics and realize the potential hidden in an individual’s DNA sequence to guide clinical decisions. In short, precision medicine is fundamentally evolutionary medicine, and integration of evolutionary perspectives into the clinic will support the realization of its full potential.

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Introduction.

Genetic disease is a necessary product of evolution (Box  1 ). Fundamental biological systems, such as DNA replication, transcription and translation, evolved very early in the history of life. Although these ancient evolutionary innovations gave rise to cellular life, they also created the potential for disease. Subsequent innovations along life’s long evolutionary history have similarly enabled both adaptation and the potential for dysfunction. Against this ancient background, young genetic variants specific to the human lineage interact with modern environments to produce human disease phenotypes. Consequently, the substrates for genetic disease in modern humans are often far older than the human lineage itself, but the genetic variants that cause them are usually unique to humans.

The advent of high-throughput genomic technologies has enabled the sequencing of the genomes of diverse species from across the tree of life 1 . Analysis of these genomes has, in turn, revealed the striking conservation of many of the molecular pathways that underlie the function of biological systems that are essential for cellular life 2 . The same technologies have also spearheaded a revolution in human genomics 3 ; currently, more than 120,000 individual whole human genome sequences are publicly available, and genome-scale data from hundreds of thousands more have been generated by consumer genomics companies 4 . Huge nationwide biobanks are also characterizing the genotypes and phenotypes of millions of people from around the world 5 , 6 , 7 . These studies are radically changing our understanding of the genetic architecture of disease 8 . It is also now possible to extract and sequence ancient DNA from remains of organisms that are thousands of years old, enabling scientists to reconstruct the history of recent human adaptation with unprecedented resolution 9 , 10 . These breakthroughs have revealed the recent, often complicated, history of our species and how it influences the genetic architecture of disease 8 , 11 . With the expansion of clinical whole-genome sequencing and personalized medicine, the influence of our evolutionary past and its implications for understanding human disease can no longer remain overlooked by medical practice; evolutionary perspectives must inform medicine 12 , 13 .

Much like a family’s medical history over generations, the genome is fundamentally a historical record. Decoding the evolution of the human genome provides valuable context for interpreting and modelling disease. This context is not limited to recent human evolution but also includes more ancient events that span life’s history. In this Review, we trace the 4 billion-year interplay between evolution and disease by illustrating how innovations during the course of life’s history have established the potential for, and inevitability of, disease. Beginning with events in the very deep past, where most genes and pathways involved in human disease originate, we explain how ancient biological systems, recent genetic variants and dynamic environments interact to produce both adaptation and disease risk in human populations. Given this scope, we cannot provide a comprehensive account of all evolutionary events relevant to human disease. Instead, our goal is to illustrate through examples the relevance of both deep and recent evolution to the study and treatment of genetic disease. Many of these key insights stem from recent discoveries, which have yet to be integrated into the broader canvas of evolutionary biomedicine (Box  2 ).

Box 1 The evolutionary necessity of disease

The definition of disease varies across biological, medical and evolutionary perspectives. Viewing disease through the lens of evolution provides a flexible and powerful framework for defining and classifying disease 12 . As illustrated in the reaction norms plotted in the figure, disease risk ( y axis) is a function of both genotype (coloured lines) and environment ( x axis).

Some genotypes lead to disease in all environments (line A); high-penetrance Mendelian disorders fall into this group. At the other extreme, disease risk may only occur in the case of a very specific pairing of environment and genotype (line D). Phenylketonuria (PKU), which manifests only in the presence of mutations that render both copies of the phenylalanine hydroxylase enzyme non-functional and a diet that includes phenylalanine, illustrates this case. Most diseases fall between these extremes (lines B and C). Disease often arises from fundamental evolutionary ‘mismatches’ between genotype and environment. For example, the high risk for obesity, a chronic disease with substantial heritability (30–40%) 177 , in many modern populations is due (at least in part) to rapid and recent changes in human lifestyle 178 , such as eating higher-calorie foods, maintaining more sedentary lifestyles and sleeping fewer hours. Here, obesity manifests due to a ‘mismatch’ between the genotype and a rapidly changing environment. Genotypes often have opposing effects on different traits. This evolutionary pattern, called antagonistic pleiotropy, often leads to disease 179 . A canonical example is balancing selection to maintain variation at the haemoglobin subunit-β ( HBB ) locus that protects against malarial disease but recessively leads to sickle cell anaemia. Antagonistic pleiotropy has also been detected in complex genetic traits, such as heart disease where alleles that increase lifetime reproductive success also increase the risk for heart disease 180 . As these examples illustrate, many modern human diseases exist because populations have not adapted to changing environments or previous adaptations lead to trade-offs between health and fitness. However, disease is not just a product of the modern world. As long as there is phenotypic variation, disease is inevitable; some individuals will be better suited to some environments (and thus healthier) than others.

Box 2 Evolutionary medicine

Evolutionary medicine is the study of how evolutionary processes have produced human traits/disease and how evolutionary principles can be applied in medicine. This Review focuses on recent advances in evolutionary genomics as they relate to our understanding of the origins and genetic basis for disease. Evolutionary medicine is a larger field that has been extensively reviewed elsewhere 12 , 26 , 181 . For context, we introduce major principles of evolutionary medicine here. Evolutionary perspectives on medicine are predicated on the idea that human diseases emerge out of the constraints, trade-offs, mismatches and conflicts inherent to complex biological systems interacting (via natural selection) with diverse and shifting environments (Box  1 ).

Evolutionary medicine has identified several categories of explanation for complex genetic diseases. The first category of evolutionary explanation is that natural selection does not result in perfect bodies but operates on relative reproductive fitness constrained by the laws of physics and the role, availability and interactions of pre-existing biological variation that shapes or constrains the subsequent course of evolution 182 , 183 . A second explanation is mismatch between our biological legacy and our modern environments 184 . Mismatch between our biological adaptations to ancestral environments and modern lifestyles contributes to many common diseases, such as obesity, diabetes and heart disease, that are promoted by sedentary lifestyles and poor nutrition 185 , 186 . For example, past exposure to calorie-poor conditions may promote metabolically efficient ‘thrifty’ gene variants that may contribute to increased obesity in calorie-rich environments. A third explanation is that of trade-offs, the idea that there are combinations of traits that cannot be simultaneously optimized by natural selection 50 , 51 . The trade-off concept is related to evolutionary constraint, but encompasses a large set of phenomena that shape trait evolution. For example, many fitness-related traits draw on common energetic reserves, and investment in one comes at the expense of another 52 . Likewise, pleiotropic genetic variants that influence multiple systems create potential for trade-offs. Furthermore, symptoms that are interpreted as disease may actually represent conditionally adaptive responses. Finally, evolutionary conflicts provide a fourth possible explanation. All multicellular organisms are aggregates of genes and genomes with different evolutionary histories and with diverse strategic interests. This means that all traits expressed by complex metazoans are a balanced compromise between different genetic elements and bodily systems 187 . Pathology can emerge out of conflict when conditions perturb these compromises.

Macroevolutionary imprints on human disease

Systems involved in disease have ancient origins.

Many of cellular life’s essential biological systems and processes, such as DNA replication, transcription and translation, represent ancient evolutionary innovations shared by all living organisms. Although essential, each of these ancient innovations generated the conditions for modern disease (Fig.  1 ). In this section, we provide examples of how several ancient innovations have created substrates for dysfunction and disease, and how considering these histories contributes to understanding the biology of disease and extrapolating results from model systems to humans.

A timeline of evolutionary events (top) in the deep evolutionary past and on the human lineage that are relevant to patterns of human disease risk (bottom). The ancient innovations on this timeline (left) formed biological systems that are essential, but are also foundations for disease. During recent human evolution (right), the development of new traits and recent rapid demographic and environmental changes have created the potential for mismatches between genotypes and modern environments that can cause disease. The timeline is schematic and not shown to scale. bya, billion years ago; kya, thousand years ago; mya, million years ago.

As a foundational (if obvious) example, the origin of self-replicating molecules 4 billion years ago formed the basis of life, but also the root of genetic diseases 12 , 14 , 15 . Similarly, asymmetric cell division may have evolved as an efficient way to handle cellular damage, but it also established the basis for ageing in multicellular organisms 16 , 17 . Myriad age-related diseases in humans, and many other multicellular organisms, are a manifestation of this first evolutionary trade-off .

The evolution of multicellularity, which has occurred many times across the tree of life, illustrates the interplay between evolutionary innovation and disease 18 . The origin of multicellularity enabled complex body plans with trillions of cells, involving innovations associated with the ability of cells to regulate their cell cycles, modulate their growth and form intricate networks of communication. But multicellularity also established the foundation for cancer 19 , 20 . Genes that regulate cell cycle control are often divided into two groups: caretakers and gatekeepers 21 , 22 . The caretakers are involved in basic control of the cell cycle and DNA repair, and mutations in these genes often lead to increased mutation rates or genomic instability, both of which increase cancer risk. Caretaker genes are enriched for functions with origins dating back to the first cells 23 . The gatekeepers appeared later, at the genesis of metazoan multicellularity 23 . The gatekeepers are directly linked to tumorigenesis through their roles in regulating cell growth, death and communication. The progression of individual tumours in a given patient is likewise informed by an evolutionary perspective. Designing treatments that account for the evolution of drug resistance and heterogeneity in tumours is a tenet of modern cancer therapy 24 , 25 , 26 , 27 , 28 , 29 .

Like multicellularity, the evolution of immune systems also set the stage for dysregulation and disease. Mammalian innate and adaptive immune systems are both ancient. Components of the innate immune system are present across metazoans and even some plants 30 , 31 , whereas the adaptive immune system is present across jawed vertebrates 32 . These systems provided molecular mechanisms for self-/non-self-recognition and response to pathogens, but they evolved in a piecemeal fashion, using many different, pre-existing genes and processes. For example, co-option of endogenous retroviruses provided novel regulatory elements for interferon response 33 . As well, it is clear that the human immune system has co-evolved with parasites, such as helminths, over millions of years. Helminth infection both induces and modulates an immune response in humans 34 .

Evolutionary analyses of development have revealed that new anatomical structures often arise by co-opting existing structures and molecular pathways that were established earlier in the history of life. For example, animal eyes, limb structure in tetrapods and pregnancy in mammals (Box  3 ) each evolved by adapting and integrating ancient genes and regulatory circuits in new ways 35 , 36 , 37 , 38 . This integration of novel traits into the existing network of biological systems gives rise to links between diverse traits via the shared genes that underlie their development and function 36 . As a result, many genes are pleiotropic — they have effects on multiple, seemingly unrelated, traits. We do not have space here to cover the full evolutionary scope of these innovations and their legacies, but just as in each of the cases described above, innovations and adaptations spanning from the origin of metazoans to modern human populations shape the substrate upon which disease appears.

Box 3 Pregnancy as a case study in evolutionary medicine

Mammalian pregnancy illustrates how consideration of a trait’s history across evolutionary time can inform our understanding of disease. Every human who ever lived experienced pregnancy, but its complexity is remarkable — it involves coordination between multiple genomes and physiological integration between individuals, and is administered by a transient organ, the placenta 188 . Furthermore, by ensuring the generational transmission of genetic information, it provides the substrate for all evolution and renewal of life itself 189 .

Macroevolutionary

Pregnancy in placental mammals, which appeared ~170 million years ago, involves physiological integration of fetal and maternal tissues via the placenta, a transient fetal-derived, extra-embryonic organ. Live birth and placentation open the door to interplay between mother and fetus over resource provisioning, with the potential for the mother to provide less than fetal demands because of other energetic needs, such as caring for other offspring. In some mammals, including humans, placentation is highly invasive, setting up a physiological tug of war between mother and fetus over provisioning. When this precarious balance is disrupted, diseases of pregnancy can occur. Poor maternal arterial remodelling during placentation limits placental invasion, which invokes a compensatory response by the distressed fetus. This imbalance results in inflammation, hypertension, kidney damage and proteinuria in the mother, and an increase in oxidative stress and spontaneous preterm birth in the fetus 190 . Pregnancy-associated maternal hypertension with proteinuria is clinically defined as pre-eclampsia with vascular aetiologies, with a poor prognosis for both mother and fetus if untreated. Understanding pre-eclampsia as the result of an evolutionary tug of war between mother and the fetus has medical implications 191 , 192 , 193 , 194 .

Human-specific

Timing of birth is key to a successful, healthy pregnancy, but little is known about the mechanisms governing the initiation of parturition. The steroid hormone progesterone and its receptors are involved in parturition in all viviparous species; however, how progesterone regulates parturition is likely to be species-specific. For example, the human progesterone receptor (PGR) exhibited rapid evolution after divergence from the last common ancestor with chimpanzees 195 , 196 . There are functional differences between the human and Neanderthal versions of the progesterone receptor 197 . The human-specific changes in the PGR influence its transcription and probably its phosphorylation 198 , 199 . Similarly, loci associated with human preterm birth have experienced diverse evolutionary forces, including balancing selection, positive selection and population differentiation 200 . The rapid and diverse types of evolutionary change observed in the PGR and some of the loci associated with preterm birth make it challenging to extrapolate analyses of their molecular functions in animal models, such as mice. In addition, humans and mice differ in reproductive strategies, morphology of the uterus, placentation, hormone production and the drivers of uterine activation 201 . For example, progesterone is produced maternally in mice throughout pregnancy, whereas in humans its production shifts to the placenta after the early stages of pregnancy. Given the unique evolutionary history of human pregnancy, many molecular aspects of pregnancy may be better studied in other model organisms or human cell-based systems.

Human population level

A central enigma of mammalian pregnancy is that the maternal immune system does not reject the foreign fetus; rather, it has not only evolved to accept the fetus but is also critical in the process of placentation 202 , 203 . The centrality of the maternal immune system in pregnancy has important medical implications. The modulation of the maternal immune system during pregnancy results in a lowered ability to clear certain infections 204 , 205 . Uterine natural killer (uNK) cells and their killer cell inhibitory receptors (KIRs) cooperate with fetal trophoblasts to regulate the maternal immune response. In addition, uNK cells are also involved in immune response to pathogens, and this dual role provides the substrate for evolutionary trade-offs. For example, the human-specific KIR AA haplotype is associated with lower birthweight and pre-eclampsia as well as with a more effective defence against Ebola virus and hepatitis 206 , 207 (Fig.  4a ). Modern human populations have variation in the diversity and identity of KIR haplotypes, probably due to selection on both placentation and host defence 208 . Infectious disease outbreaks, therefore, place a unique selective pressure on pregnancy. Severe outbreaks of infectious diseases, such as malaria, often produce significant shifts in population-level allele frequencies in pregnancy-related genes, such as FLT1 in malaria-endemic populations of Tanzania 209 . The varying pressures from infectious disease are likely to contribute to variation in risk of pregnancy-related diseases between modern populations.

Medical implications

Although ancient macroevolutionary innovations may seem far removed from modern human phenotypes, their imprint remains on the human body and genome. Understanding the constraints they impose can provide insight into mechanisms of disease.

Mapping the origins and evolution of traits and identifying the genetic networks that underlie them are critical to the accurate selection of model systems and extrapolation to human populations. Failure to consider the evolutionary history of homologous systems, their phylogenetic relationships and their functional contexts in different organisms can lead to inaccurate generalization. Instead, when considering a model system, key evolutionary questions about both the organism and the trait of interest can indicate how translatable the research will be to humans 39 , 40 . For example, is the similarity between the trait in humans and the trait in the model system due to shared ancestry, that is, homology ? The presence of homology in a human gene or system of study suggests potential as a model system; however, homology alone is not sufficient justification. Environmental and life history factors shape traits, and divergence between species complicates the simple assumption that homology provides genetic or mechanistic similarity. Thus, homology must be supplemented by understanding of whether the evolutionary divergence between humans and the proposed model led to functional divergence. For example, the rapid evolution of the placenta and variation in reproductive strategy across mammals have made it challenging to extrapolate results about the regulation of birth timing from model organisms, such as mouse, to humans (Box  3 ). More broadly, differences in genetic networks that underlie the development of homologous traits across mammals explain why the majority of successful animal trials fail to translate to human clinical trials 41 , 42 . Molecular mechanisms of ancient systems, such as DNA replication, can be studied using phylogenetically distant species; however, ‘humanizing’ these models to research human-specific aspects of traits may not be possible and comparative studies of closely related species may be required 40 .

Although evolutionary divergence in homologous traits is an impediment to the direct translation of findings from a model system to humans, understanding how these evolutionary differences came about can also yield insights into disease mechanisms. For example, intuition would suggest that large animals (many cells and cell divisions) with long lifespans (many ageing cells), such as elephants and whales, would be at increased risk for developing cancer. However, size and lifespan are not significantly correlated with cancer risk across species; despite their large size, elephants and whales do not have a higher risk of developing cancer 43 , 44 . Why is this so? Recent studies of the evolution of genes involved in the DNA damage response in elephants have revealed mechanisms that may contribute to cancer resistance. An ancient leukaemia inhibiting factor pseudogene ( LIF6 ) regained its function in the ancestor of modern elephants. This gene works in conjunction with the tumour suppressor gene TP53 , which has increased in copy number in elephants, to reduce elephants’ risk for cancer despite their large body size 45 , 46 . This illustrates a basic life history trade-off: selection has created mechanisms for cancer suppression and somatic maintenance in large vertebrates that are not needed in small short-lived vertebrates. Studying such seeming paradoxes, especially those with clear contrasts to human disease risk, will shed light on broader disease mechanisms and suggest targets for functional interventions with translation potential.

Human-specific evolution

Human adaptation, trade-offs and disease.

The macroevolutionary events described above created the foundation of genetic disease, but considering the more recent changes that occurred during the evolutionary history of the human lineage is necessary to illuminate the full context of human disease. Comparisons between humans and their closest living primate relatives, such as chimpanzees, have revealed diseases that either do not appear in other species or take very different courses 47 . We are beginning to understand the genetic differences underlying some of these human-specific conditions, with particular insights into infectious diseases.

The last common ancestors of humans and chimpanzees underwent a complex speciation event that is likely to have involved multiple rounds of gene flow between ~12 and 6 million years ago (mya) 48 . Over the millions of years after this divergence, climatic, demographic and social pressures drove the evolution of many physical and behavioural traits unique to the human lineage, including bipedalism (~7 mya), lack of body hair (~2–3 mya) and larger brain volume relative to body size (~2 mya) 12 , 47 . These traits evolved in a diverse array of hominin groups, mainly in Africa, although some of these species, such as Homo erectus , ventured into Europe and Asia.

These human adaptations developed on the substrate of tightly integrated systems shaped by billions of years of evolution, and thus beneficial adaptations with respect to one system often incurred trade-offs in the form of costs on other linked systems 49 . The trade-off concept derives from a branch of evolutionary biology known as life history theory. It is based on the observation that organisms contain combinations of traits that cannot be simultaneously optimized by natural selection 50 , 51 . For example, many fitness-related traits draw on common energetic reserves, and investment in one comes at the expense of another 52 . Large body size may improve survival in certain environments, but it comes at the expense of longer development and lower numerical investment in reproduction.

The trade-off concept is clinically relevant because it dispenses with the notion of a single ‘optimal’ phenotype or fitness state for an individual 49 , 53 , 54 . Given the interconnected deep evolution of the human body, many diseases are tightly linked, in the sense that decreasing the risk for one increases the risk for the other. Such diametric diseases and the trade-offs that produce them are the starkest when there is competition within the body for limited resources; for example, energy used for reproduction cannot be used for growth, immune function or other energy-consuming survival processes 54 . The molecular basis for diametric diseases often results from antagonistic pleiotropy at the genetic level — when a variant has contrasting effects on multiple bodily systems. In extreme cases, some diseases that manifest well after reproductive age, for example, Alzheimer disease, have been less visible to selection and, thus, potentially more susceptible to trade-offs. Cancer and neurodegenerative disorders also exhibit this diametric pattern, where cancer risk is inversely associated with Alzheimer disease, Parkinson disease and Huntington disease. This association is hypothesized to be mediated by differences in the neuronal energy use and trade-offs in cell proliferation and apoptosis pathways 49 . Similarly, osteoarthritis (breakdown of cartilage in joints often accompanied by high bone mineral density) and osteoporosis (low bone mineral density) rarely co-occur. Their diametric pattern reflects, at least in part, different probabilities across individuals of mesenchymal stem cells within bone marrow to develop into osteoblasts versus non-bone cells such as adipocytes 49 , 55 . In another example, a history of selection for a robust immune response can now lead to an increased risk for autoimmune and inflammatory diseases, especially when coupled with new environmental mismatches 49 , 54 . Other examples of trade-offs are found throughout the human body, manifesting in risk for diverse diseases, including psychiatric and rheumatoid disorders 49 , 56 .

Just as adaptations in deep evolutionary time created new substrates for disease, evolutionary pressures exerted on the human lineage established the foundation for complex cognitive capabilities, but they also established the potential for many neuropsychiatric or neurodevelopmental diseases. For example, genomic structural variants enabled functional innovation in the brain through the emergence of novel genes 57 , 58 , 59 , 60 . Many human-specific segmental duplications influence genes that are essential to the development of the human brain, such as SRGAP2C and ARHGAP11B . Both of these genes function in cortical development and may be involved in the expansion of human brain size 61 , 62 , 63 . The human-specific NOTCH2NL is also hypothesized to have evolved from a partial duplication event, and is implicated in increased output during human corticogenesis, another potential key contributor to human brain size 59 , 60 . Although these structural variants were probably adaptive 58 , they may have also predisposed humans to neuropsychiatric diseases and developmental disorders. Copy number variation in the region flanking ARHGAP11B , specifically a microdeletion at 15q13.3, is associated with risk for intellectual disability, autism spectrum disorder (ASD), schizophrenia and epilepsy 58 , 64 . Duplications and deletions of NOTCH2NL and surrounding regions are implicated in macrocephaly and ASD or microcephaly and schizophrenia, respectively 59 . These trade-offs also play out at the protein domain level. For example, the Olduvai domain (previously known as DUF1220) is a 1.4-kb sequence that appears in ~300 copies in the human genome; this domain has experienced a large human-specific increase in copy number. These domains appear in tandem arrays in neuroblastoma breakpoint family ( NBPF ) genes, and have been associated with both increased brain size and neuropsychiatric diseases, including autism and schizophrenia 65 . These examples suggest that the genomic organization of these human-specific duplications may have enabled human-specific changes in brain development while also increasing the likelihood of detrimental rearrangements that cause human disease 59 , 64 . Furthermore, genomic regions associated with neuropsychiatric diseases have experienced human-specific accelerated evolution and recent positive selection, providing additional evidence for the role of recent evolutionary pressures on human disease risk 66 , 67 . Schizophrenia-associated loci, for example, are enriched near human accelerated regions (HARs) that are conserved in non-human primates 68 . Variation in HARs has also been associated with risk for ASD, possibly through perturbations of gene regulatory architecture 69 .

Human immune systems have adapted in response to changes in environment and lifestyles over the past few million years; however, the rapid evolution of the immune system may have left humans vulnerable to certain diseases, such as HIV-1 infection. A similar virus, simian immunodeficiency virus (SIV), is found in chimpanzees and other primates, and studies in the early 2000s found evidence of AIDS-like symptoms (primarily a reduction in CD4 + T cells) in chimpanzees infected with SIV. Although the effects of SIV in chimpanzees mirror some of the effects of HIV in humans 70 , captive chimpanzees infected with HIV-1 do not typically develop AIDS and have better clinical outcomes. The differences in outcome are influenced by human-specific immune evolution. For example, humans have lost expression of several Siglecs, cell surface proteins that binds sialic acids, in T lymphocytes compared with great apes 71 . In support of this hypothesis, human T cells with high Siglec-5 expression survive longer after HIV-1 infection 72 . Moreover, there is a possible role for the rapidly evolving Siglecs in other diseases, such as epithelial cancers, that differentially affect humans relative to closely related primates 73 , 74 .

Another human-specific immune change is the deletion of an exon of CMP- N -acetylneuraminic acid hydroxylase ( CMAH ) leading to a difference in human cell surface sialoglycans compared with other great apes 75 , 76 , 77 . The change in human sialic acid to an N -acetylneuraminic acid (Neu5Ac) termination, rather than N -glycolylneuraminic acid (Neu5Gc), may have been driven by pressure to escape infection by Plasmodium reichenowi , a parasite that binds Neu5Gc and causes malaria in chimpanzees. Conversely, the prevalence of Neu5Ac probably made humans more susceptible to infection by the malaria parasite Plasmodium falciparum , which binds to Neu5Ac 78 , 79 , and another human-specific pathology: typhoid fever 80 . Typhoid toxin binds specifically and is cytotoxic to cells expressing Neu5Ac glycans. Thus, the deletion of CMAH was likely to have been selected for by pressure from pathogens, but has in turn enabled other human-specific diseases such as malaria and typhoid fever 81 . The rapid evolution of the human immune system creates the potential for human-specific disease. As a result, human-specific variation in many other human immune genes influences human-specific disease risk 82 , 83 .

These examples from recent human evolution highlight the ongoing interplay of genetic variation, adaptation and disease. Understanding the evolutionary history of traits along with the aetiology of related diseases can help identify and evaluate risks for unintended consequences of treatments due to trade-offs. For example, ovarian steroids have pleiotropic effects stimulating both bone growth and mitosis in breast tissues to mobilize calcium stores during lactation 54 . However, later in life this link gives rise to a clinical trade-off. Hormone replacement therapy in postmenopausal women reduces the risk for osteoporosis and ovarian cancer, but also, as a result of its effects on breast tissue, increases the risk for breast cancer. Given the commonality of the trade-off between maintenance and proliferation, this is just one of many examples of cancer risk emerging as a result of trade-offs in immune, reproductive and metabolic systems 56 , 84 . Pregnancy is also rife with clinically relevant trade-offs given the interaction between multiple individuals and genomes (mother, father and fetus) with different objectives (Box  3 ). Trade-offs at the cellular level also have medical implications. For example, cellular senescence is a necessary and beneficial part of many basic bodily responses, but the accumulation of senescent cells underlies many ageing-related disorders. Thus, individuals with different solutions to this trade-off may have very different ‘molecular’ versus ‘chronological’ ages 85 .

Identifying such trade-offs by studying disease and treatment response is of great interest, but is challenging for several reasons: the number of possible combinations of traits to consider is large; many humans must have experienced the negative effects; and data must be available on both traits in the same individuals. Here, evolution paired with massive electronic health record (EHR)-linked biobanks 5 , 86 , 87 provides a possible solution. By considering the evolutionary context and potential linkages between traits, the search space of possible trade-offs can be constrained. Then, diametric traits can be tested for among individuals in the EHRs by performing phenome-wide association studies (PheWAS) either on traits or genetic loci of interest and looking for inverse relationships 88 . The mechanisms underlying the observed associations could then be evaluated in model systems and, if validated, anticipated in future human treatments.

In addition to trade-offs, evolutionary analyses can help us identify therapeutic targets for uniquely human diseases. A small subset of humans infected with HIV never progress to AIDS — a resistance phenotype that has been generally attributed to host genomics 89 , 90 , 91 . Identifying and understanding the genes that contribute to non-progression is of great interest in the development of vaccines and treatments for HIV infection. Genome-wide association studies (GWAS) and functional studies have supported the role of the MHC class I region, specifically the HLA-B*27/B*57 molecules, in HIV non-progression 92 , 93 , 94 . Comparative genomics with chimpanzees identified a chimpanzee MHC class I molecule functionally analogous to that of the non-progressors that contains amino acid substitutions that change binding affinity for conserved areas of the HIV-1 and SIV viruses. Evolutionary analysis of this region suggests that these substitutions are the result of an ancient selective sweep in chimpanzee genomes that did not occur in humans 95 . This analysis not only helps us understand how humans are uniquely susceptible to HIV progression but also highlights functional variation in the MHC that are potential targets of medical intervention.

Recent human demographic history

Most genetic variants are young, but have diverse histories.

The complex demographic history of modern humans in the past 200,000 years has created differences in the genetic architecture of and risk for specific diseases among human populations. With genomic sequences of thousands of humans from diverse locations, we can compare genetic information over time and geography to better understand the origins and evolution of both individual genetic variants and human populations 96 , 97 , 98 . The vast majority of human genetic variants are not shared with other species 99 . Demographic events such as bottlenecks , introgression and population expansion shaped the genetic composition of human populations, whereas rapid introduction of humans into new environments and the subsequent adaptations created potential for evolutionary mismatches (Figs  2 , 3 ).

Representative genes that have experienced local adaptive evolution over the past 100,000 years as humans moved across the globe. We focus on adaptations that also produced the potential for disease due to trade-offs or mismatches with modern environments. For each, we list the evolutionary pressure, the trait(s) influenced and the associated disease(s). The approximate regions where the adaptations occurred are indicated by blue circles. Arrows represent the expansion of human populations, and purple shading represents introgression events with archaic hominins. Supplementary Table S1 presents more details and references. COVID-19, coronavirus disease 2019; G6PD, glucose-6-phosphate dehydrogenase; UV, ultraviolet.

Ancient human migrations, introgression events with other archaic hominins and recent population expansions have all contributed to the introduction of variants associated with human disease. Schematic of human evolutionary history, where the branches represent different human populations and the branch widths represent population size (top left). Letter labels refer to the processes illustrated in parts a – d . a | Human populations migrating out of Africa maintained only a subset of genetic diversity present in African populations. The resulting out-of-Africa bottleneck is likely to have increased the fraction of deleterious, disease-associated variants in non-African populations. Coloured circles represent different genetic variants. Circles marked with X denote deleterious, disease-associated variants. b | When anatomically modern humans left Africa, they encountered other archaic hominin populations. Haplotypes introduced by archaic introgression events (illustrated in grey) contained Neanderthal-derived variants (denoted by red circles) associated with increased disease risk in modern populations. c | In the last 10,000 years, the burden of rare disease-associated variants (denoted by yellow circles) has increased due to rapid population expansion. d | Modern human individuals with admixture in their recent ancestry, such as African Americans, can have differences in genetic risk for disease, because of each individual’s unique mix of genomic regions with African and European evolutionary ancestry. For example, each of the three admixed individuals depicted have the same proportions of African and European ancestry, but do not all carry the disease-associated variant found at higher frequency in European populations (illustrated by yellow circles). Summarizing clinical risk for a patient requires a higher resolution view of evolutionary ancestry along the genome and improved representation of genetic variation from diverse human populations.

Approximately 200,000 years ago, ‘ anatomically modern humans ’ (AMHs) first appeared in Africa. This group had the key physical characteristics of modern human groups and exhibited unique behavioural and cognitive abilities that enabled rapid improvements in tool development, art and material culture. Approximately 100,000 years ago, AMH groups began to migrate out of Africa. The populations ancestral to all modern Eurasians are likely to have left Africa tens of thousands of years later 98 , but quickly spread across Eurasia. Expansions into the Americas and further bottlenecks are thought to have occurred between 35,000 and 15,000 years ago. The details and uncertainties surrounding these origin and migration events are more extensively reviewed elsewhere 98 .

Populations that experience bottlenecks and founder effects have a higher mutation load than populations that do not, largely due to their lower effective population sizes reducing the efficacy of selection 100 (Fig.  3a ). During this dispersal, the migrant human populations harboured less genetic variation than was present in Africa. The reduction in diversity caused by the out-of-Africa and subsequent bottlenecks shaped the genetic landscape of all populations outside Africa.

AMHs did not live in isolation after migration out of Africa. Instead, there is evidence of multiple admixture events with other archaic hominin groups, namely Neanderthals and Denisovans 101 , 102 . Modern non-African populations derive approximately 2% of their ancestry from Neanderthals, with some Asian populations having an even higher proportion of archaic hominin ancestry (Fig.  3b ). African populations have only a small amount of Neanderthal and Denisovan ancestry, largely from back migration from European populations with archaic ancestry 103 . However, there is evidence of admixture with other, as yet unknown, archaic hominins in the genomes of modern African populations 104 , 105 , 106 .

Following their expansion around the globe, humans have experienced explosive growth over the past 10,000 years, in particular in modern Eurasian populations 107 , 108 (Fig.  3c ). Growth in population size modifies the genetic architecture of traits by increasing the efficacy of selection and generating many more low-frequency genetic variants. Although the impact of rare alleles is not completely understood, they often have a deleterious role in variation in traits in modern populations 109 . Although there is still debate about the combined effects of these recent demographic differences, a consensus is emerging that they are likely to have only minor effects on the efficacy of selection and the mutation load between human populations 100 , 110 , 111 , 112 , 113 , 114 . Nonetheless, there are substantial differences in allele frequency between populations that are relevant to disease risk 115 .

The exposure of humans to new environments and major lifestyle shifts, such as agriculture and urbanization, created the opportunity for adaptation 96 , 116 . Ancient DNA sequencing efforts coupled with recent statistical advances are beginning to enable the linking of human adaptations to specific environmental shifts in the recent past 96 , 117 , 118 . However, these rapid environmental changes also created new patterns of complex disease. Mismatch between our biological suitability for ancestral environments and modern environments accounts for the prevalence of many common diseases, such as obesity, diabetes or heart disease that derive from sedentary lifestyles and poor nutrition. The ancestral susceptibility model proposes that ancestral alleles that were adapted to ancient environments can, in modern populations, increase the risk for disease 119 , 120 . Supporting this hypothesis, both ancestral and derived alleles increase disease risk in modern humans 121 , 122 . However, underscoring the importance of recent demographic history, patterns of risk for ancestral and derived alleles differ in African and European populations, with ancestral risk alleles at higher frequencies in African populations 115 .

The different evolutionary histories of modern human individuals and populations described in the previous section influence disease susceptibilities and outcomes. Perhaps most striking are the mismatches and trade-offs resulting from recent immune system adaptations. Classic examples include genetic variants conferring resistance to malaria also causing sickle cell-related diseases in homozygotes 96 , 123 , or the predominantly African G1 and G2 variants in APOL1 protecting against trypanosomes and ‘sleeping sickness’ but leading to chronic kidney disease in individuals with these genotypes 96 . Similarly, a variant in CREBRF that is thought to have improved survival for people in times of starvation is now linked to obesity and type 2 diabetes 124 . In a study of ancient European populations, a variant in SLC22A4 , the ergothioneine transporter, that may have been selected for to protect against deficiency of ergothioneine (an antioxidant) is also associated with gastrointestinal problems such as coeliac disease, ulcerative colitis and irritable bowel syndrome 118 . The variant responsible did not reach high frequency in European populations until relatively recently, and current disease associations are likely to be new, perhaps as a result of mismatches with the current environment 118 . The possibility of mismatch is further supported by the varying prevalence of coeliac disease between human populations related to population-specific selection for several risk alleles 82 . Indeed, recent studies suggest that there is a relationship between ancestry and immune response, with individuals of African ancestry demonstrating stronger responses. This could be the result of selective processes in response to new environments for European populations, or a larger pathogen burden in Africa now leading to a higher instance of inflammatory and autoimmune disorders. This is still an open area of research, and more evidence is needed before strong conclusions can be drawn 125 .

In modern human environments, there is also a mismatch between the current low parasite infection levels and the immune system that evolved under higher parasite load. This mismatch is hypothesized to contribute to the increase in inflammatory and autoimmune diseases seen in modern humans 34 . For example, loci associated with ten different inflammatory diseases, including Crohn’s disease and multiple sclerosis, show evidence of selection consistent with the hygiene hypothesis 126 . Furthermore, recent positive selection on variants in the type 2 immune response pathway favoured alleles associated with susceptibility to asthma 127 . This suggests that recent evolutionary processes may have led to elevated or altered immune responses at the expense of increased susceptibility to inflammatory and autoimmune diseases. This insight has broad clinical implications, including the potential targeted use of helminths and natural products for immune modulation in patients with chronic inflammatory disease 128 , 129 .

Archaic introgression is relevant to modern medicine because alleles introduced by these evolutionary events continue to have an impact on modern populations even though the archaic hominin lineages are now extinct (Fig.  3b ). Archaic hominins had considerably lower effective population sizes than AMHs, and thus they probably carried a larger fraction of weakly deleterious mutations than AMHs 101 . As a result, Neanderthal introgression is predicted to have substantially increased the genetic load of non-African AMHs 130 , 131 . Large-scale sequencing efforts, in combination with analysis of clinical biobanks and improved computational methods, have revealed the potential impacts of introgressed DNA on modern human genomes. Several recent studies link regions of archaic admixture in modern populations with a range of diseases, including immunological, neuropsychiatric and dermatological phenotypes 102 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 . This demonstrates the functional impact of introgressed sequence on disease risk in non-African humans today. However, some of these associations may be influenced by linked non-Neanderthal alleles 140 . For example, in addition to alleles of Neanderthal origin, introgression also reintroduced ancestral alleles that were lost in modern Eurasian populations prior to interbreeding (for example, in the out-of-Africa bottleneck) 141 . Some introgressed alleles may have initially lessened adverse effects from migration to northern climates, dietary changes and introduction to novel pathogens 117 , 142 , 143 . For example, Neanderthal alleles contribute to variation in innate immune response across populations 125 , 132 , 134 , 144 and probably helped AMHs adapt to new viruses, in particular RNA viruses in Europe 145 . However, due to recent demographic and environmental changes, some previously adaptive Neanderthal alleles may no longer provide the same benefits 146 . For example, there is evidence that an introgressed Neanderthal haplotype increases risk for SARS-CoV-2 (ref. 147 ).

Physicians regularly rely on proxies for our more recent evolutionary history in the form of self-reported ancestry in their clinical practice; however, these measures fail to capture the complex evolutionary ancestry of each individual patient. For example, two individuals who identify as African Americans may both have 15% European ancestry, but this ancestry will be at different genomic loci and from different ancestral European and African populations (Fig.  3d ). Thus, one may carry a disease-increasing European ancestry allele whereas the other does not. Mapping fine-scale genetic ancestry across patients’ genomes can improve our ability to summarize clinically relevant risk 148 , but such approaches require broad sampling across populations and awareness of human diversity (Box  4 ). The profound need to increase the sampling of diverse groups is demonstrated by the lack of diversity in genomic studies, and the potential for health disparities caused by the over-representation of European-ancestry populations 149 , 150 , 151 (Fig.  4 ). In 2016, 81% of GWAS data were from studies conducted on European populations 149 . Although this is an improvement from 96% in 2009, most non-European populations still lack appropriate representation. The problem is more extreme for many phenotypes or traits of interest. For example, only 1.2% of the studies in a survey of 569 GWAS on neurological phenotypes included individuals of African ancestry 150 , 152 .

a | Interactions between the maternal killer cell inhibitory receptor (KIR) genotype and the fetal trophoblasts illustrate evolutionary trade-offs in pregnancy. Birthweight is under stabilizing selection in human populations. The interaction between maternal KIR genotypes (a diversity of which are maintained in the population) and the fetal trophoblasts influence birthweight. African (AFR) populations, relative to European (EUR) populations, maintain larger proportions of the KIR AA haplotype 176 , which is associated with improved maternal immune response to some viral challenges; however, it is also associated with low birthweight. Alternatively, the KIR BB haplotype is associated with higher birthweight but increased risk of pre-eclampsia. b | Current strategies for predicting genetic risk are confounded by a lack of inclusion of diverse human populations. Thus, they are more likely to fail in genetic risk prediction in populations that are under-represented in genetic databases. For example, polygenic risk score (PRS) models trained on European populations often perform poorly when applied to African populations. This poor performance stems from the fact that the genetic diversity of African populations, differences in effect sizes between populations and differential evolutionary pressures are not taken into account. The weights for each variant (blue circles) in the PRS derived from genome-wide association studies are signified by w1, w2 and w3. c | Population-specific adaptation and genetic hitch-hiking can produce different disease risk between populations. Haplotypes with protective effects against disease may rise to high frequency in specific populations through genetic hitch-hiking with nearby alleles under selection for a different trait. For example, selection for lighter skin pigmentation caused a haplotype that carried a variant associated with lighter skin (blue circle) to increase in frequency in European populations compared with African populations. This haplotype also carried a variant protective against prostate cancer (blue triangle).

Ancestry biases in genomic databases and GWAS propagate through other strategies that are designed to translate population genetic insights to the clinic, such as polygenic risk scores (PRSs) 153 , 154 (Fig.  4b ). PRSs hold the promise of predicting medical outcomes from genomic data alone. However, the evolutionary perspective suggests that the genetic architecture of diseases should differ between populations due to the effects of the demographic and environmental differences discussed above. Indeed, many PRSs generalize poorly across populations and are subject to biases 155 , 156 . Prioritization of Mendelian disease genes is also challenging in under-represented populations. Generally, African-ancestry individuals have significantly more variants, yet we know less about the pathogenicity of variants that are absent from or less frequent in European populations 157 . Patients of African and Asian ancestry are currently more likely than those of European ancestry to receive ambiguous genetic test results after exome sequencing or be told that they have variants of uncertain significance (VUS) 158 . Indeed, disease-causing variants of African origin are under-represented in common databases 159 . This under-representation covers a range of phenotypic traits and outcomes, including interpreting the effects of CYP2D6 variants on drug response 160 , 161 , risk identification and classification for breast cancer across populations 162 , and disparate effects of GWAS associations for traits including body mass index (BMI) and type 2 diabetes in non-European populations 163 . In a study on hypertrophic cardiomyopathy, benign variants in African Americans were incorrectly classified as pathogenic on the basis of GWAS results from a European ancestry cohort. Inclusion of individuals of African descent in the initial GWAS could have prevented these errors 164 .

Box 4 Evolutionary medicine in clinical practice

Evolutionary perspectives have yet to be integrated into most areas of clinical practice. Notable exceptions involve diseases in which evolutionary processes act over short timescales to drive the progression of disease. For example, knowledge of the intense selective pressures underlying the evolution of drug resistance of microorganisms and the growth of tumours now guides the application of precise therapies and drug delivery strategies 210 , 211 , 212 , 213 . These examples illustrate how an evolutionary perspective can improve patient outcomes. However, they differ from the main focus of this article — the influence of human evolution on common genetic disease — where the relevant evolutionary processes have acted over thousands or millions of years.

Nonetheless, accounting for the innovations, adaptations and trade-offs that have shaped human populations should be considered in the clinical application of precision medicine to complex disease. For example, polygenic risk scores (PRSs) are a burgeoning technology with great clinical potential to stratify individuals by risk and enable preventative care 154 , 214 , but they have a fundamental dependence on underlying evolutionary processes. Individuals have different genetic backgrounds based on their ancestry, and these different histories alter the relationships between genotypes, environmental factors and risk of disease (Fig.  4 ). From this evolutionary perspective, PRSs should not be expected to generalize across populations and environments given the varied demographic histories of human populations that shape genetic variation 155 , 156 , 215 . Indeed, failure to account for this diversity in the application of PRSs and other genetics-based prediction methods can cause substantial harm and contribute to health disparities by producing misdiagnosis, improper drug dosing and inaccurate risk predictions 149 , 150 , 151 , 158 , 160 , 161 , 162 , 163 , 164 . An evolutionary approach is integral to solving this problem. PRSs must be developed and critically evaluated across the full range of human diversity to determine when genetic factors can provide an accurate risk profile for individuals. This is crucial in individuals with recent admixture in their ancestry, as risk profiles can vary based on the unique patterns of ancestry in each individual (Fig.  3 ). If genetic information is to inform personalized predictions about disease risk, explicitly considering evolution by quantifying genetic ancestry must be a critical component of this process.

The development of PRSs provides a timely and illustrative case study of how evolutionary perspectives can move from research contexts to inform clinical application. It also highlights the pitfalls of ignoring the implications of human evolutionary history when generalizing findings across populations. The establishment of a new technology (genome sequencing) enabled the measurement of a signal that is informative about disease risk (genetic variation) but is also influenced by evolutionary history. The knowledge gained from 100 years of basic research in population genetics about how human populations have evolved provides the context for these new technologies and the path towards ensuring that new treatments are not biased against specific populations.

Beyond providing context for existing analyses and treatments, new approaches are needed to translate our understanding of the history of human evolution from basic research to clinical relevance. In the main text, we highlight examples of how trade-offs, caused by competition for resources or antagonistic pleiotropy, may produce contrasting effects on disease risk within an individual. Similarly, new environmental conditions, such as a new pathogen, may rapidly create genetic mismatches in some populations. We propose that evolution-guided analysis of large-scale phenotype databases, such as those in electronic health record (EHR)-linked biobanks, are a promising approach for identifying novel patterns of diametric disease or mismatches in patient populations. For example, if a gene with pleiotropic functions is targeted by a treatment, such as a drug, knowledge of the gene’s evolution and functions can suggest specific phenotypes to test for diametric occurrence in the biobank. Given the overlapping evolutionary histories of molecular pathways involved in most traits, we anticipate that many clinically relevant trade-offs are waiting to be discovered.

Conclusions and future perspectives

All diseases have evolutionary histories, and the signatures of those histories are archived in our genomes. Recent advances in genomics are enabling us to read these histories with high accuracy, resolution and depth. Insights from evolutionary genomics reveal that there is not one answer to the question of why we get sick. Rather, diseases affect patchworks of ancient biological systems that evolved over millennia, and although the systems involved are ancient, the variation that is relevant for human disease is recent. Furthermore, evolutionary genomics approaches have the power to identify potential mechanisms, pathways and networks and to suggest clinical targets. In this context, we argue that an evolutionary perspective can aid the implementation of precision medicine in the era of genome sequencing and editing 165 (Box  4 ).

Combining knowledge of evolutionary events along the human lineage with results from recent genomic studies provides an explanatory framework beyond descriptions of disease risk or association. For example, a recent analysis of the higher incidence of prostate cancer among men of African ancestry not only discovered a set of genetic variants associated with increased risk, but also used measures of selection to propose an evolutionary explanation of genetic hitch-hiking for the lower incidence in non-African populations 166 . Haplotypes with protective effects against prostate cancer may have risen to higher frequency in non-African populations because of selection on the nearby variants associated with skin pigmentation (Fig.  4c ). Thus, evolutionary perspectives not only help answer the question of how we get sick but also why we get sick.

As the genetic information available from diverse populations increases, we can specifically map the genetics of traits in different populations and more precisely define disease risk on an individual basis 167 , 168 . However, we emphasize that environmental and social factors are major determinants of disease risk that often contribute more than genetics, and thus must be prioritized. Studying diverse human populations will provide additional power to discover trait-associated loci and understand genetic architecture across different environmental exposures and evolutionary histories 150 , 169 . For example, a GWAS with small sample size in a Greenlandic Inuit population found a variant in a fatty-acid enzyme that affects height in both this population and European populations 170 . Previous GWAS probably missed this variant due to its low frequency in European populations (0.017 compared with 0.98 in the Inuit); nevertheless, it has a much greater effect on height than other variants previously identified through GWAS 170 . Similarly, a recent study of height in 3,000 Peruvians identified another variant with an even greater influence on height 171 . The growth of large DNA biobanks in which hundreds of thousands of patients’ EHRs are linked to DNA samples represents a substantial untapped resource for evolutionary medicine 5 , 86 , 87 . These data enable testing of the functional effects of genetic variants on diverse traits at minimal additional cost. Shifting from single-ancestry GWAS to trans-ethnic or multi-ethnic GWAS will capitalize on the benefits of both a larger sample size and the inherent diversity of human populations for replication of established signals and discovery of new ones 172 , 173 , 174 , 175 .

Although evolutionary assumptions are tacit in medical practice, until recently self-reported family history remained the best representation of our evolutionary ancestry’s imprint on our disease risk. However, a family history cannot fully capture the complex evolutionary and demographic history of each individual. New technologies now enable the collection and interpretation of an individual’s family history in a much longer and complementary form — their genome. New data and methods are substantially increasing the resolution and depth with which these histories can be quantified, providing opportunities for evolution to inform medical practice.

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Acknowledgements

The authors thank L. Muglia and members of the Capra, Rokas and Abbot laboratories for helpful discussions. They also thank the National Institutes of Health (NIH) (T32LM012412 to M.L.B. and R35GM127087 to J.A.C.), the Burroughs Wellcome Fund Preterm Birth Initiative (A.R. and J.A.C.), the March of Dimes Prematurity Research Center Ohio Collaborative (P.A., A.R. and J.A.C.) and the American Heart Association (A.A.) for support.

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Supplementary table s1.

All aspects of the genetic variants that influence variation of a trait in a population. Commonly studied attributes of genetic architecture include the number of genetic loci that influence a trait, the frequency of these variants, the magnitudes of their effects and how they interact with one another and the environment. The genetic architectures of traits vary along these axes; for example, some traits are influenced by many common variants of small effect, whereas others are driven by a few rare variants of large effect.

Representations of how the expressed phenotype for a genotype varies in response to a range of environments. Reaction norms can be used to illustrate many of the concepts described in this Review, including evolutionary mismatches and antagonistic pleiotropy.

Adaptations that are advantageous for one phenotype have costs for others. Evolutionary trade-offs often result when genes influence multiple phenotypes (pleiotropy) or when there is a limited resource that must be apportioned to different functions. Because of trade-offs, there is not an optimal genotype across all environments.

Pertaining to pleiotropy, which is when a genetic locus (for example, a gene or regulatory element) has effects on multiple unrelated phenotypes. Antagonistic pleiotropy results when a locus has a beneficial effect on one trait and a detrimental effect on another.

Similarity in traits, bodily structures or genomic sequences due to shared ancestry between two species. Homology is considered when selecting model systems to study a particular phenotype; however, it does not guarantee underlying functional or mechanistic similarity.

Linked diseases for which decreasing the risk for one increases the risk for the other, such as protection from infectious disease increasing risk for autoimmune disease. Diametric disorders result from evolutionary trade-offs.

An animal that gives birth to live young, rather than laying eggs.

(HARs). Genomic loci conserved across mammalian species that experienced an increase in substitution rate specific to the human lineage. Genetic changes in HARs are responsible for some attributes of human-specific biology.

Rapid decreases in the size of populations that lead to a decrease in genetic diversity. Genetic bottlenecks can be caused by environmental factors (such as famine or disease) or demographic factors (such as migration). The ancestors of most modern non-African populations experienced a bottleneck as they left Africa, which is often referred to as the out-of-Africa bottleneck.

The flow of genetic material between two species through interbreeding followed by backcrossing. Analyses of ancient DNA have revealed that introgression was common in human history over the past several hundred thousand years.

(AMHs). Individuals, both modern and ancient, with the physical characteristics of humans ( Homo sapiens ) living today.

Reduced genetic diversity as a result of a small number of individuals establishing a new population from a larger original population. Founder effects can lead to genetic conditions that were rare in the original population becoming common in the new population. Serial founder effects occurred as anatomically modern humans spread out of Africa and colonized the world.

The component of the genetic load contributed by recent deleterious variants; other factors that contribute to the overall genetic load include the amount of heterozygote advantage and inbreeding.

The creation of novel genotypes from interbreeding between two genetically differentiated populations.

Ancient individuals on the human lineage, such as Neanderthals and Denisovans, that diverged before the origin of anatomically modern humans. Use of this terminology is established in human evolutionary genetics, but is not consistent across fields due to historical differences in the use of taxonomic terms and the fluidity of the species concept in the presence of substantial introgression.

A model proposing that ancestral alleles adapted to ancient environments can increase disease risk in modern environments due to evolutionary mismatches. Many human populations are likely to be subject to such mismatches due to rapidly changing environments.

A hypothesis proposing that immune systems adapted for environments with a high pathogen load are now mismatched to current environments with low pathogen load. This mismatch is further hypothesized to contribute to the higher incidence of autoimmune and inflammatory diseases.

The decrease in population fitness caused by the presence of non-optimal alleles compared with the most fit genotype: ( W max  –  W mean )  /  W max , where W max is the maximum possible fitness and W mean is the average fitness over all observed genotypes.

(PRSs). Results of a mathematical model to estimate the genetic risk of a disease for an individual based on the sum of the effects of all their genetic variants as estimated in a genome-wide association study. The clinical utility of PRSs is a topic of current debate (Box  4 ).

A disease caused by a variant in a single gene, such as sickle cell anaemia, cystic fibrosis and phenylketonuria. Mendelian (also known as monogenic) disorders are usually rare and follow simple dominant or recessive inheritance patterns.

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Benton, M.L., Abraham, A., LaBella, A.L. et al. The influence of evolutionary history on human health and disease. Nat Rev Genet 22 , 269–283 (2021). https://doi.org/10.1038/s41576-020-00305-9

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September 1, 2020

15 min read

How Scientists Discovered the Staggering Complexity of Human Evolution

Darwin would be delighted by the story his successors have revealed

By Kate Wong

Pascal Blanchet

I n 1859, 14 years after the founding of this magazine, Charles Darwin published the most important scientific book ever written. On the Origin of Species revolutionized society's understanding of the natural world. Challenging Victorian dogma, Darwin argued that species were not immutable, each one specially created by God. Rather life on Earth, in all its dazzling variety, had evolved through descent from a common ancestor with modification by means of natural selection. But for all of Darwin's brilliant insights into the origins of ants and armadillos, bats and barnacles, one species is conspicuously neglected in the great book: his own. Of Homo sapiens , Darwin made only a passing mention on the third-to-last page of the tome, noting coyly that "light will be thrown on the origin of man and his history." That's it. That is all he wrote about the dawning of the single most consequential species on the planet.

It was not because Darwin thought humans were somehow exempt from evolution. Twelve years later he published a book devoted to that very subject, The Descent of Man . In it, he explained that discussing humans in his earlier treatise would have served only to further prejudice readers against his radical idea. Yet even in this later work, he had little to say about human origins per se, instead focusing on making the case from comparative anatomy, embryology and behavior that, like all species, humans had evolved. The problem was that there was hardly any fossil record of humans to provide evidence of earlier stages of human existence. Back then, "the only thing you knew was what you could reason," says paleoanthropologist Bernard Wood of the George Washington University.

To his credit, Darwin made astute observations about our kind and predictions about our ancient past based on the information that was available to him. He argued that all living humans belong to one species and that its "races" all descended from a single ancestral stock. And pointing to the anatomical similarities between humans and African apes, he concluded that chimpanzees and gorillas were the closest living relatives of humans. Given that relationship, he figured, early human ancestors probably lived in Africa.

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Since then, Wood says, "the evidence has come in." In the past century and a half, science has confirmed Darwin's prediction and pieced together a detailed account of our origins. Paleoanthropologists have recovered fossil hominins (the group that comprises H. sapiens and its extinct relatives) spanning the past seven million years. This extraordinary record shows that hominins indeed got their start in Africa, where they evolved from quadrupedal apes into the upright-walking, nimble-fingered, large-brained creatures we are today.

And the archaeological record of hominin creations, which encompasses roughly half that time, charts their cultural evolution—from early experiments with simple stone tools to the invention of symbols, songs and stories—and maps our ancestors' spread across the globe. The fossils and artifacts demonstrate that for most of the period over which our lineage has been evolving, multiple hominin species walked the earth. Studies of modern and ancient DNA have generated startling insights into what happened when they encountered one another.

Neandertals were the first extinct hominin species to be recognized in the fossil record and the first to yield ancient DNA. Credit: Javier Trueba/Science Source

The human saga, we now understand, is far more intricate than scholars of yore envisioned. The tidy tropes of our prehistory have collapsed under the weight of evidence: there is no single missing link that bridges apes and humankind, no drumbeat march of progress toward a predestined goal. Our story is complicated, messy and random. Yet it still can be accommodated under Darwin's theory of evolution and in fact further validates that framework.

This is not to say scientists have it all figured out. Many questions remain. But whereas the origin of humans was once an uncomfortable speculation in Darwin's big idea, it is now among the best-documented examples of evolution's transformative power.

We humans are strange creatures. We walk upright on two legs and possess supersized brains, we invent tools to meet our every need and express ourselves using symbols, and we have conquered every corner of the planet. For centuries scientists have sought to explain how we came to be, our place in the natural world.

This quest was often distorted by racist ideologies. Consider the era leading up to the birth of Darwin's bombshell theory. In the 1830s, while a young Darwin was making his momentous voyage onboard the Beagle , a movement was underway to promote the idea that the various modern human groups around the globe—races—had separate origins. To build the case for polygenism, as the theory is known, scientists such as Samuel Morton in Philadelphia collected skulls from people across the world and measured their sizes and shapes, falsely believing those attributes to be proxies for intelligence. When they ranked the specimens from superior to inferior, Europeans would conveniently come out on top and Africans on the bottom. "There was a desire to provide scientific justification for political and power structures," says anthropological geneticist Jennifer Raff of the University of Kansas. "It was science in the service of slavery and colonialism."

Although Darwin's work came down firmly on the side of monogenism—the idea that all humans share a common ancestor—it was nonetheless co-opted to support notions about racial superiority. Social Darwinism, for one, misapplied Darwin's ideas about the struggle for existence in natural selection to human society, providing a pseudoscientific rationalization for social injustice and oppression. Darwin himself did not subscribe to such views. In fact, his opposition to slavery might have been a driving force in his research agenda, according to his biographers Adrian Desmond and James Moore.

By the time Darwin published The Descent of Man , in 1871, the idea that humans had evolved from a common ancestor with apes was already gaining traction in the scientific community thanks to books published in the 1860s by English biologist Thomas Henry Huxley and Scottish geologist Charles Lyell. Still, the fossil evidence to support this claim was scant. The only hominin fossils known to science were a handful of remains a few tens of thousands of years old that had been recovered from sites in Europe. Some were H. sapiens; others would eventually be recognized as a separate but very closely related species, Homo neanderthalensis . The implication was that fossils of more apelike human ancestors were out there somewhere in the world, awaiting discovery. But the suggestion by Darwin, like Huxley before him, that those ancestors would be found in Africa met with resistance from scholars who saw Asia as a more civilized birthplace for humankind and emphasized similarities between humans and Asia's gibbons.

Perhaps it should come as no surprise, then, that when the first hominin fossil significantly older and more primitive than those from Europe turned up, it came not from Africa but from Asia. In 1891 Dutch anatomist Eugène Dubois discovered remains on the Indonesian island of Java that he thought belonged to the long-sought missing link between apes and humans. The find, which he named Pithecanthropus erectus , spurred further efforts to root humankind in Asia. (We now know that Dubois's fossil was between 700,000 and one million years old and belonged to a hominin that was much more humanlike than apelike, Homo erectus .)

Two decades later the search turned to Europe. In 1912 amateur archaeologist Charles Dawson reported that he had found a skull with a humanlike cranium and an apelike jaw in an ancient gravel pit near the site of Piltdown in East Sussex, England. Piltdown Man, as the specimen was nicknamed, was a leading contender for the missing link until it was exposed in 1953 as a fraudulent pairing of a modern human skull with an orangutan's lower jaw.

Piltdown so seduced scholars with the prospect of making Europe the seat of human origins that they all but ignored an actual ancient hominin that turned up in Africa, one even older and more apelike than the one Dubois discovered. In 1925, 43 years after Darwin's death, anatomist Raymond Dart published a paper describing a fossil from Taung, South Africa, with an apelike braincase and humanlike teeth. Dart named that fossil—a youngster's skull now known to be around 2.8 million years old— Australopithecus africanus , "the southern ape from Africa." But it would take nearly 20 years for the scientific establishment to accept Dart's argument that the so-called Taung Child was of immense significance: the fossil linked humans to African apes.

Evidence of humanity's African origins has accumulated ever since. Every hominin trace older than 2.1 million years—and there are now quite a few of them—has come from that continent.

Even as fossil discoveries proved Darwin right about the birthplace of humanity, the pattern of our emergence remained elusive. Darwin himself depicted evolution as a branching process in which ancestral species divide into two or more descendant species. But a long-standing tradition of organizing nature hierarchically—one that dates back to Plato and Aristotle's Great Chain of Being—held sway, giving rise to the notion that our evolution unfolded in linear fashion from simple to complex, primitive to modern. Popular imagery reflected and reinforced this idea, from a caricature in Punch's Almanack for 1882 showing a progression from earthworm to Darwin, to the iconic monkey-to-man illustration that appeared in the 1965 Time-Life book Early Man and became known as the March of Progress.

From the rich assortment of fossils and artifacts recovered from around the world in the past century, however, paleoanthropologists can now reconstruct something of the timing and pattern of human evolution. The finds clearly show that this single-file scheme is no longer tenable. Evolution does not march steadily toward predetermined goals. And many hominin specimens belong not in our direct line of ancestry but on side branches of humankind—evolutionary experiments that ended in extinction.

From the outset, our defining traits evolved not in lockstep but piecemeal. Take our mode of locomotion, for example. H. sapiens is what anthropologists call an obligate biped—our bodies are built for walking on two legs on the ground. We can climb trees if we need to, but we have lost the physical adaptations that other primates have to arboreal life. Fragmentary fossils of the oldest known hominins— Sahelanthropus tchadensis from Chad, Orrorin tugenensis from Kenya and Ardipithecus kadabba from Ethiopia—show that our earliest ancestors emerged by around seven million to 5.5 million years ago. Although they are apelike in many respects, all of them exhibit characteristics associated with walking on two legs instead of four. In Sahelanthropus , for example, the hole in the base of the skull through which the spinal cord passes has a forward position suggestive of an upright posture. A bipedal gait may thus have been one of the very first traits that distinguished hominins from ancestral apes.

Yet our forebears appear to have retained traits needed for arboreal locomotion for millions of years after they first evolved the ability to walk on two legs. Australopithecus afarensis , which lived in eastern Africa from 3.85 million to 2.95 million years ago and is famously represented by the skeleton known as Lucy, discovered in 1974, was a capable biped. But it had long, strong arms and curved fingers—features associated with tree climbing. It would be another million years before modern limb proportions evolved and committed hominins to life on the ground, starting with early H. erectus in Africa (sometimes called Homo ergaster ).

The brain evolved on quite a different schedule. Over the course of human evolution, brain size has more than tripled. A comparison of the braincase of A. afarensis with that of the much older Sahelanthropus , however, shows that hardly any of that growth occurred in the first few million years of human evolution. In fact, most of the expansion took place in the past two million years, perhaps enabled by a feedback loop in which advances in technology—stone tools and the like—gave hominins access to more nutritious foods such as meat, which could fuel a larger and thus more energetically demanding brain, which in turn could dream up even better technology, and so on. Shifts in the shape and structure of the brain accompanied these gains, with more real estate allocated to regions involved in language and long-range planning, among other advanced cognitive functions.

This mosaic pattern of hominin evolution in which different body parts evolved at different rates produced some surprising creatures. For instance, Australopithecus sediba from South Africa, dated to 1.98 million years ago, had a humanlike hand attached to an apelike arm, a big birth canal but a small brain, and an advanced ankle bone connected to a primitive heel bone.

Sometimes evolution even doubled back on itself. When one examines a hominin fossil, it can be difficult to discern whether the species retained a primitive trait such as small brain size from an earlier ancestor or whether it lost the characteristic and then re-evolved it. But the strange case of Homo floresiensis may well be an example of the latter. This member of the human family lived on the island of Flores in Indonesia as recently as 50,000 years ago yet looked in many ways like some of the founding members of our genus who lived more than two million years earlier. Not only did H. floresiensis have a small body, but it also possessed a remarkably tiny brain for Homo , about the size of a chimp's. Scientists' best guess is that this species descended from a brawnier, brainer Homo species that got marooned on Flores and evolved its diminutive size as an adaptation to the limited food resources available on its island home. In so doing, H. floresiensis seems to have reversed what researchers once considered a defining trend of Homo 's evolution: the inexorable expansion of the brain. Yet despite its small brain, H. floresiensis still managed to make stone tools, hunt animals for food and cook over fires.

Adding to the complexity of our story, it is now clear that for most of the time over which humans have been evolving, multiple hominin species walked the earth. Between 3.6 million and 3.3 million years ago, for example, at least four varieties of hominins lived in Africa. Paleoanthropologist Yohannes Haile-Selassie of Arizona State University's Institute of Human Origins and his colleagues have recovered remains of two of them, A. afarensis and Australopithecus deyiremeda , as well as a possible third creature known only from a distinctive fossil foot, in an area called Woranso-Mille in Ethiopia's Afar region. How they managed to share the landscape is a subject of current investigation. "Competing species could co-exist if there were plenty of resources or if they were exploiting different parts of the ecosystem," Haile-Selassie says.

Later, between roughly 2.7 million and 1.2 million years ago, representatives of our genus, Homo —large-brained tool users with dainty jaws and teeth—shared the grasslands of southern and eastern Africa with a radically different branch of humanity. Members of the genus Paranthropus , these hominins had massive teeth and jaws, flaring cheekbones and crests atop their heads that anchored powerful chewing muscles. Here the co-existence is somewhat better understood: whereas Homo seems to have evolved to exploit a wide variety of plants and animals for food, Paranthropus specialized in processing tough, fibrous plant foods.

H. sapiens overlapped with other kinds of humans, too. When our species was evolving in Africa 300,000 years ago, several other kinds of hominins also roamed the planet. Some, such as the stocky Neandertals in Eurasia, were very close relatives. Others, including Homo naledi in South Africa and H. erectus in Indonesia, belonged to lineages that diverged from ours in the deep past. Even as recently as 50,000 years ago, hominin diversity was the rule, with the Neandertals, the mysterious Denisovans from Asia, tiny H. floresiensis and another small hominin— Homo luzonensis from the Philippines—all at large.

Such discoveries make for a much more interesting picture of human evolution than the linear account that has dominated our view of life. But they raise a nagging question: How did H. sapiens end up being the sole surviving twig on what was once a luxuriant evolutionary bush?

Here are the facts of the case. We know from fossils found at the site of Jebel Irhoud in Morocco that our species originated in Africa by at least 315,000 years ago. By around 200,000 years ago it began making forays out of Africa, and by 40,000 years ago it had established itself throughout Eurasia. Some of the places H. sapiens colonized were occupied by other hominin species. Eventually the other folks all disappeared. By around 30,000 to 15,000 years ago, with the end of the Neandertals in Europe and the Denisovans in Asia, H. sapiens was alone in the world.

Researchers have often attributed the success of our species to superior cognition. Although the Neandertals actually had slightly larger brains than ours, the archaeological record seemed to indicate that only H. sapiens crafted specialized tools and used symbols, suggesting a capacity for language. Perhaps, the thinking went, H. sapiens won out by virtue of sharper foresight, better technology, more flexible foraging strategies and bigger social networks for support against hard times. Alternatively, some investigators have proposed, maybe H. sapiens waged war on its rivals, exterminating them directly.

But recent discoveries have challenged these scenarios. Neandertal technology, archaeologists have learned, was far more varied and sophisticated than previously thought. Neandertals, too, made jewelry and art, crafting pendants from shells and animal teeth and painting abstract symbols on cave walls. Moreover, they might not have been our only enlightened kin: a 500,000-year-old engraved shell from Java suggests that H. erectus also possessed symbolic thought. If archaic hominins had many of the same mental faculties as H. sapiens , why did the latter prevail?

The conditions under which H. sapiens got its start might have played a role. Fossil and archaeological data suggest that our species mostly stayed in Africa for the first couple of hundred thousand years of its existence. There, some experts argue, it evolved as a population of interconnected subgroups spread across the continent that split up and reunited again and again over millennia, allowing for periods of evolution in isolation followed by opportunities for interbreeding and cultural exchange. This evolutionary upbringing might have honed H. sapiens into an especially adaptable hominin. But that is not the whole story, as we now know from genetics.

Analyses of DNA have revolutionized the study of human evolution. Comparing the human genome with the genomes of the living great apes has shown conclusively that we are most closely related to chimpanzees and bonobos, sharing nearly 99 percent of their DNA. And large-scale studies of DNA from modern-day human populations across the globe have illuminated the origins of modern human variation, overturning the centuries-old notion that races are biologically discrete groups with separate origins. "There have never been pure populations or races," Raff says. Modern human variation is continuous, and most variation exists within populations rather than between them—the product of our demographic history as a species that originated in Africa with populations that mixed continuously as they migrated around the world.

More recently, studies of ancient DNA have cast new light on the world of early H. sapiens as it was when other hominin species were still running around. In the late 1990s geneticists began recovering small amounts of DNA from Neandertal and early H. sapiens fossils. Eventually they succeeded in getting entire genomes not only from Neandertals and early H. sapiens but also from Denisovans, who are known from just a few fragmentary fossils from Siberia and Tibet. By comparing these ancient genomes with modern ones, researchers have found evidence that our own species interbred with these other species. People today carry DNA from Neandertals and Denisovans as a result of these long-ago encounters. Other studies have found evidence of interbreeding between H. sapiens and unknown extinct hominins from Africa and Asia for whom we have no fossils but whose distinctive DNA persists.

Mating with other human species might have aided H. sapiens' success. Studies of organisms ranging from finches to oak trees have shown that hybridization with local species can help colonizing species flourish in novel environments by giving them useful genes. Although scientists have yet to figure out the functions of most of the genes people today carry from extinct hominins, they have pinpointed a few, and the results are intriguing. For instance, Neandertals gave H. sapiens immunity genes that might have helped our species fend off novel pathogens it encountered in Eurasia, and Denisovans contributed a gene that helped people adapt to high altitudes. H. sapiens may be the last hominin standing, but it got a leg up from its extinct cousins.

Scientists have many more pieces of the human-origins puzzle than they once did, but the puzzle is now vastly bigger than it was previously understood to be. Many gaps remain, and some may never close. Take the question of why we evolved such massive brains. At around 1,400 grams, the modern human brain is considerably larger than expected for a primate of our body size. "The singularity is why it's interesting—and why it's impossible to answer scientifically," Wood observes. Some experts have suggested that hominin brains ballooned as they adapted to climate fluctuations between wet and dry conditions, among other explanations. But the problem with trying to answer "why" questions about the evolution of our unique traits, Wood says, is that there is no way to evaluate the proposed explanations empirically: "There isn't a counterfactual. We can't go back to three million years ago and not change the climate."

Other mysteries may yield to further investigation, however. For example, we do not yet know what the last common ancestor of humans and the Pan genus that includes chimps and bonobos looked like. Genomic and fossil data suggest that the two lineages diverged between eight million and 10 million years ago—up to three million years before the oldest known hominin lived—which means that paleoanthropologists may be missing a substantial chunk of our prehistory. And they have hardly any fossils at all of Pan , which has been evolving along its own path just as long as we have. Insights may come from a project currently underway in central Mozambique, where Susana Carvalho and Ren Bobe of the University of Oxford and their colleagues are hunting for fossil primates, including hominins, in sediments older than the ones that yielded Sahelanthropus, Orrorin and Ardipithecus .

Later stages of the human story are riddled with unknowns, too. If H. sapiens was interbreeding with the other hominin species it encountered, as we now know it was, were these groups also exchanging culture? Might H. sapiens have introduced Neandertals to novel hunting technology and artistic traditions—or vice versa? New techniques for retrieving ancient DNA and proteins from otherwise unidentifiable fossils and even cave sediments are helping researchers determine which hominin species were active and when at key archaeological sites.

One wonders where the next discovery will take us in the quest to understand who we are and where we come from. We may have found our place in nature, located our twig on the shrub, but we are still searching for ourselves. We're only human, after all.

Credit: Moritz Stefaner and Christian Lässer For more context, see “ Visualizing 175 Years of Words in Scientific American ”

Kate Wong is an award-winning science writer and senior editor at Scientific American focused on evolution, ecology, anthropology, archaeology, paleontology and animal behavior. She is fascinated by human origins, which she has covered for more than 25 years. Recently she has become obsessed with birds. Her reporting has taken her to caves in France and Croatia that Neandertals once called home, to the shores of Kenya's Lake Turkana in search of the oldest stone tools in the world, to Madagascar on an expedition to unearth ancient mammals and dinosaurs, to the icy waters of Antarctica, where humpback whales feast on krill, and on a "Big Day" race around the state of Connecticut to find as many bird species as possible in 24 hours. Kate is co-author, with Donald Johanson, of Lucy's Legacy: The Quest for Human Origins . She holds a bachelor of science degree in biological anthropology and zoology from the University of Michigan. Follow Wong on X (formerly Twitter) @katewong

Human Evolution

Six million years of human evolution.

Human evolution is the lengthy process of change by which people originated from apelike ancestors. Scientific evidence shows that the physical and behavioral traits shared by all people originated from apelike ancestors and evolved over a period of approximately six million years.

Paleoanthropology is the scientific study of human evolution which investigates the origin of the universal and defining traits of our species. The field involves an understanding of the similarities and differences between humans and other species in their genes, body form, physiology, and behavior. Paleoanthropologists search for the roots of human physical traits and behavior. They seek to discover how evolution has shaped the potentials, tendencies, and limitations of all people.

What Can Human Fossils Tell Us?

Early human fossils and archeological remains offer the most important clues about this ancient past. These remains include bones, tools and any other evidence (such as footprints, evidence of hearths , or butchery marks on animal bones) left by earlier people. Usually, the remains were buried and preserved naturally. They are then found either on the surface (exposed by rain, rivers, and wind erosion) or by digging in the ground. By studying fossilized bones, scientists learn about the physical appearance of earlier humans and how it changed. Bone size, shape, and markings left by muscles tell us how those predecessors moved around, held tools, and how the size of their brains changed over a long time.

Archeological evidence refers to the things earlier people made and the places where scientists find them. By studying this type of evidence, archeologists can understand how early humans made and used  tools and lived in their environments.

Humans and Our Evolutionary Relatives

Humans are primates . Physical and genetic similarities show that the modern human species, Homo sapiens, has a very close relationship to another group of primate species, the apes. Modern humans and the great apes (large apes) of Africa – chimpanzees (including bonobos, or so-called “pygmy chimpanzees”) and gorillas – share a common ancestor that lived between 8 and 6 million years ago.

Humans first evolved in Africa, and much of human evolution occurred on that continent. The  fossils of early humans who lived between 6 and 2 million years ago come entirely from Africa. Early humans first migrated out of Africa into Asia probably between 2 million and 1.8 million years ago. They entered Europe somewhat later, between 1.5 million and 1 million years. Species of modern humans populated many parts of the world much later. For instance, people first came to Australia probably within the past 60,000 years and to the Americas within the past 15,000 years or so.

Most scientists currently recognize some 15 to 20 different species of early humans. Scientists do not all agree, however, about how these species are related or which ones simply died out. Many early human species – certainly the majority of them – left no living descendants. Scientists also debate over how to identify and classify particular species of early humans, and about what factors influenced the evolution and extinction of each species.

Human Characteristics

One of the earliest defining human traits, bipedalism – the ability to walk on two legs – evolved over 4 million years ago. Other important human characteristics – such as a large and complex brain, the ability to make and use tools, and the capacity for language  – developed more recently. Many advanced traits -- including complex symbolic expression, art , and elaborate cultural diversity – emerged mainly during the past 100,000 years. The beginnings of agriculture and the rise of the first civilizations occurred within the past 12,000 years.

Smithsonian Research Into Human Evolution

The Smithsonian’s Human Origins Program explores the universal human story at its broadest time scale. Smithsonian anthropologists research many aspects of human evolution around the globe, investigating fundamental questions about our evolutionary past, including the roots of human adaptability.

For example, Paleoanthropologist Dr. Rick Potts – who directs the Human Origins Program – co-directs ongoing research projects in southern and western Kenya and southern and northern China that compare evidence of early human behavior and environments from eastern Africa to eastern Asia. Rick’s work helps us understand the environmental changes that occurred during the times that many of the fundamental characteristics that make us human  - such as making tools and large brains – evolved, and that our ancestors were often able to persist through dramatic climate changes. Rick describes his work in the video Survivors of a Changing Environment .

Dr. Briana Pobiner is a Prehistoric Archaeologist whose research centers on the evolution of human diet (with a focus on meat-eating), but has included topics as diverse as cannibalism in the Cook Islands and chimpanzee carnivory. Her research has helped us understand that at the onset of human carnivory over 2.5 million years ago some of the meat our ancestors ate was scavenged from large carnivores, but by 1.5 million years ago they were getting access to some of the prime, juicy parts of large animal carcasses. She uses techniques similar to modern day forensics for her detective work on early human diets.

Paleoanthropologist Dr. Matt Tocheri conducts research into the evolutionary history and functional morphology of the human and great ape family, the Hominidae. His work on the wrist of Homo floresiensis , the so-called “hobbits” of human evolution discovered in Indonesia, received considerable attention worldwide after it was published in 2007 in the journal Science. He now co-directs research at Liang Bua on the island of Flores in Indonesia, the site where Homo floresiensis was first discovered.

Geologist Dr. Kay Behrensmeyer has been a long-time collaborator with Rick Potts’ human evolution research at the site of Olorgesailie in southern Kenya. Kay’s role with the research there is to help understand the environments of the sites at which evidence for early humans – in the form of stone tools as well as fossils of the early humans themselves – have been found, by looking at the sediments of the geological layers in which the artifacts and fossils have been excavated.

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Introduction

Science and science-based technologies have transformed modern life. They have led to major improvements in living standards, public welfare, health, and security. They have changed how we view the universe and how we think about ourselves in relation to the world around us.

Biological evolution is one of the most important ideas of modern science. Evolution is supported by abundant evidence from many different fields of scientific investigation. It underlies the modern biological sciences, including the biomedical sciences, and has applications in many other scientific and engineering disciplines.

As individuals and societies, we are now making decisions that will have profound consequences for future generations. How should we balance the need to preserve the Earth's plants, animals, and natural environment against other pressing concerns? Should we alter our use of fossil fuels and other natural resources to enhance the well-being of our descendants? To what extent should we use our new understanding of biology on a molecular level to alter the characteristics of living things?

None of these decisions can be made wisely without considering biological evolution. People need to understand evolution, its role within the broader scientific enterprise, and its vital implications for some of the most pressing social, cultural, and political issues of our time.

Science and technology are so pervasive in modern society that students increasingly need a sound education in the core concepts, applications, and implications of science. Because evolution has and will continue to serve as a critical foundation of the biomedical and life sciences, helping students learn about and understand the scientific evidence, mechanisms, and implications of evolution are fundamental to a high-quality science education.

Science and religion are different ways of understanding. Needlessly placing them in opposition reduces the potential of both to contribute to a better future.

Agriculture

By recovering seeds from different archaeological sites and noticing changes in their characteristics over the centuries, scientists have hypothesized how wheat was altered by humans over time. About 11,000 years ago, people in the Middle East began growing plants for food rather than relying entirely on the wild plants and animals they could gather or hunt. These early farmers began saving seeds from plants with particularly favorable traits and planting those seeds in the next growing season. Through this process of "artificial selection," they created a variety of crops with characteristics particularly suited for agriculture. For example, farmers over many generations modified the traits of wild wheat so that seeds remained on the plant when ripe and could easily be separated from their hulls. Over the next few millennia, people around the world used similar processes of evolutionary change to transform many other wild plants and animals into the crops and domesticated animals we rely on today.

In recent years, plant scientists have begun making hybrids of wheat with some of their wild relatives from the Middle East and elsewhere. Using these hybrids, they have bred wheat varieties that are increasingly resistant to droughts, heat, and pests. Most recently, molecular biologists have been identifying the genes in the DNA of plants that are responsible for their advantageous traits so that these genes can be incorporated into other crops. These advances rely on an understanding of evolution to analyze the relationships among plants and to search for the traits that can be used to improve crops.

Combating New Infectious Diseases

In late 2002 several hundred people in China came down with a severe form of pneumonia caused by an unknown infectious agent. Dubbed "severe acute respiratory syndrome," or SARS, the disease soon spread to Vietnam, Hong Kong, and Canada and led to hundreds of deaths. In March 2003 a team of researchers at the University of California, San Francisco, received samples of a virus isolated from the tissues of a SARS patient. Using a new technology known as a DNA microarray, within 24 hours the researchers had identified the virus as a previously unknown member of a particular family of viruses -- a result confirmed by other researchers using different techniques. Immediately, work began on a blood test to identify people with the disease (so they could be quarantined), on treatments for the disease, and on vaccines to prevent infection with the virus.

An understanding of evolution was essential in the identification of the SARS virus. The genetic material in the virus was similar to that of other viruses because it had evolved from the same ancestor virus. Furthermore, knowledge of the evolutionary history of the SARS virus gave scientists important information about the disease, such as how it is spread. Knowing the evolutionary origins of human pathogens will be critical in the future as existing infectious agents evolve into new and more dangerous forms.

7 strange and surprising ways that humans have recently evolved

When we learn about evolution in school, it feels old and slow. (Charles Darwin's impressive beard later in life probably doesn't help here.)

But evolution is very much still happening today — and it's happening to us.

Right here, right now.

It's too soon to say what humans will look like a few thousand years from now, but here are some of the most recent quirks — and even superpowers — we've acquired thanks to the power of selection.

1. Drinking milk as adults

Drinking milk is one of the defining traits of mammals, but humans are the only species on Earth to digest it after infancy, though even now,  more than 75%  of the world's population is still lactose intolerant.

After weaning, all other mammals, and most humans, cease producing lactase, the enzyme necessary to break down lactose, milk sugar.

But a mutation that appeared on the plains of Hungary about 7,500 years ago allowed some humans to digest milk into adulthood. We probably started with cheeses — cheddar and feta contain less lactose than fresh milk and softer cheeses , and Parmesan contains almost no lactose.

This may seem nutritionally inconsequential (though delicious) now, but the ability to digest incredibly calorie-dense dairy products was incredibly useful for humans surviving the cold winters of Europe.

2. Disease resistance

Evolution is about the survival of the fittest — and a big part of evolutionary fitness is not dying from a disease before you've had children. So it makes sense that evolution would be giving us a boost against some common diseases.

The most-studied disease we've been outrunning lately is malaria. If you've taken an introductory biology course lately, you may remember a strange connection with sickle-cell anemia . That's because there's a specific gene that, if you have one copy, will protect your red blood cells from invasion by the malaria parasite — but two copies will distort red blood cells and block their passage through blood vessels.

But that isn't the only trick that's evolved in the face of malaria. There are also more than a hundred slightly different genes that cause a shortage of a protein involved in breaking down red blood cells. That makes it harder for the malaria parasite to sneak into a red blood cell. Another type of mutation that's been spreading lately blocks malaria parasites from hanging out in the placenta.

And it's not just malaria — evolution has helped spread adaptations that protect against leprosy, tuberculosis, and cholera in certain populations as well. Some scientists have suggested that living in cities helps this process along.

3. Blue eyes

Blue eyes are another recent-evolved trait and scientists have determined it came from a mutation in a single ancestor 6,000-10,000 years ago.

The mutation affected the OCA2 gene , which codes the protein necessary for producing melanin, which gives our skin, hair and eyes their color. This essentially "switched off" the ability to have brown eyes by limiting the melanin produced in the iris, and "diluting" the eye color from brown to blue.

Having lighter eyes didn't give anyone a particular survival advantage, but because the gene for blue eyes operates similarly to a recessive trait ( though it's a little more complicated ), blue-eyed fathers could better guarantee that their children were, in fact, their own.

4. High-altitude breathing

Tibetans live in one of the least hospitable, and therefore one of the last populated areas on the planet: the Himalayan mountains. And their ability to handle the low-oxygen levels up there is not due to mere hardiness — it's coded into their genes.

One study compared indigenous Tibetans, who live at altitudes above 10,000 feet in the Himalayan highlands, with Han Chinese from Beijing, who are closely related genetically but live right around sea level elevation.

The researchers found that the Tibetans' blood was genetically predisposed to produce more of the oxygen-transporting hemoglobin protein. Still up for debate is when this mutation occurred, but some geneticists have estimated it happening as recently as 3,000 years ago (though unsurprisingly, archaeologists push that date much further back).

5. Missing wisdom teeth

It's not just oral surgeons who are removing wisdom teeth (third molars) from human mouths — evolution is playing a part too.

On our evolutionary road to becoming humans, our big brains crowded our skulls and narrowed our jaws, making it difficult for the third row of molars to emerge from the gums.

And after we began cooking our food and developed agriculture thousands of years ago, our diet became softer. This switch to soft grains and starches required less strenuous chewing than our past hunter-gatherer diet. This meant our jaw muscles didn't grow as strong as they used to, keeping the wisdom teeth beneath the gums increasing the risk of painful and deadly infection.

A few thousand years ago, a mutation popped up that prevented wisdom teeth from growing at all. Now one in four people are missing at least one wisdom tooth. The people who are most likely to be missing at least one wisdom tooth are the Inuit of the northernmost regions of Greenland, Canada, and Alaska.

6. Alcohol flush reaction

Alcohol flush reaction, also known as the "Asian glow," is not only a real thing, it's also a recently evolved trait that may protect East Asian populations from a deadly  cancer.

In about 36% of East Asians (Chinese, Japanese, and Koreans), drinking alcohol causes facial flushing and nausea. This is due to a deficiency in the enzyme known as  ALDH2 .

While this may cause some social challenges amidst peers of more heavy-drinking ancestries, it's an important indicator of a serious health risk. People with an ALDH2 deficiency are also at greater risk of developing esophageal cancer from drinking alcohol.

Curiously, scientists believe this mutation occurred after the development of agriculture — which made producing alcohol possible.

7. Shrinking brains

We think pretty highly of our brains, but it turns out they've actually been shrinking for more than 20,000 years . The total change adds up to a piece the size of a tennis ball in an adult male. But scientists don't think that means we're getting dumber.

One theory is that each of us relies more on the structure of society to help us get by, so we don't need as much brain space as individuals. But as we've domesticated animals like cats and dogs, we've watched their brains shrink too. That means some scientists think smaller brains may actually mark more peaceful animals.

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AP®︎/College Biology

Course: ap®︎/college biology   >   unit 7, evolution: natural selection and human selection article.

• Artificial selection and domestication
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What is evolution?

• natural selection
• genetic drift, and

Natural selection - one of the mechanisms of evolution

An example of natural selection at work - antibiotic resistance, what is artificial selection or selective breeding, an example of artificial selection - dog breeding.

• Purebred is a type of dog that comes from a lineage of the same dog breed and that has never mated with another breed. For example, a purebred german shepherd is all german shepherd and nothing else.
• A cross-breed dog is a dog that was the offspring of two different types of purebreds. Let’s say your purebred german shepherd mated with a purebred husky. The resulting offspring would be a cross-breed of half german shepherd, half husky.
• Finally, mixed-breeds are a combination of multiple breeds, where their parents were not purebreds. There are too many possible combinations to count!

Common misconceptions about evolution

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Understanding Evolution

Your one-stop source for information on evolution

Lines of Evidence: The Science of Evolution

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Observations of evolution in the wild

As we would expect based on evolutionary theory, populations evolve in response to their surroundings. Much of this evolution happened long ago and was not observed by humans – and consequently, we have to investigate many lines of evidence to reconstruct this history.  However, in some cases evolution has occurred in the wild over timescales and in places that we can make direct observations of – that is, we humans know what a species was like at one point in time, and then later observe that it has changed in ways that can only be attributed to evolution.

For example, house sparrows were brought to North America from Europe in the nineteenth century. Since then, genetic variation within the species, and the different selective pressures present in different habitats have allowed them to adapt to different parts of the continent.  Thus, modern house sparrows in the north are larger and darker colored than those in the south. Darker colors absorb sunlight better than light colors and larger size allows less surface area per unit volume, thus reducing heat loss — both advantages in a cold climate. This is an example of  natural selection  acting upon different populations, producing micro-evolution on a continental scale. And it is one that humans have been around to observe firsthand. We were there when the sparrows were intentionally released in the 1800s, and today we can directly observe that sparrows from different parts of the continent are different from one another, as shown by this map.

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• To learn more about how natural selection operates, visit Evo 101 .

There are many other cases in which evolution has occurred on timescales that we can directly observe.  These include:

• Squirrels, mosquitoes, and other organisms evolving in response to climate change
• Fish evolving in response to pollutants
• Bedbugs evolving resistance to pesticides
• Mussels evolving in response to predation 
• Clover evolving in response to urbanized landscapes 
• Crickets evolving in response to a parasitic fly
• Bacteria evolving resistance to antibiotics
• Blackcap birds and Galapagos finches diverging into lineages with distinct traits

Reviewed and updated, June 2020.

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Are humans still evolving?

In this Spotlight, we ask whether modern humans are still evolving or whether we have stepped out of the path of natural selection.

Charles Darwin published his totemic work on evolution — On the Origin of Species — in 1859.

Based on the concept of natural selection, Darwin’s book provided scientists with a new toolkit for understanding the place that humans and animals occupy in the natural world.

The tome also gave clues as to where their earthly origins may lie.

According to Darwin’s thesis, evolution is slow and incremental with tiny genetic changes spread tens of thousands of years apart gently pushing forward changes in species.

In 2000, the paleontologist Stephen Jay Gould famously declared that “there’s been no biological change in humans in 40,000 or 50,000 years,” suggesting that evolution in humans is imperceptibly slow or has perhaps stopped altogether.

The British naturalist and broadcaster Sir David Attenborough concurred, even arguing that birth control and abortion have contributed to a halt in physical evolution among humans.

“We stopped natural selection as soon as we started being able to rear 90–95 percent of our babies that are born. We are the only species to have put a halt to natural selection, of its own free will, as it were,” he told the British magazine The Radio Times in 2013, adding that our species has instead ensured our continued survival through accelerating cultural evolution:

“Stopping natural selection is not as important, or depressing, as it might sound — because our evolution is now cultural […] We can inherit a knowledge of computers or television, electronics, airplanes, and so on.”

Natural selection requires variation

Both positions have been hotly contested. For instance, Dr. Ian Rickard — from Durham University in the United Kingdom — responded to Attenborough’s claims by pointing out that while abortion and birth control may mean that some people are having children while others are not, natural selection does not end here.

Rather, it places a renewed focus on the genetic material that is being passed along by those who are having children. Writing in The Guardian , Dr. Rickard explains, “Natural selection requires variation. It needs some individuals to thrive more than others.”

“So the improved survival prospects around the world over recent decades and centuries drastically decreases the potential for natural selection to work in those populations. But that is not the end of the argument. Even if everyone survives to the same age, there is still variation for natural selection to work with. Natural selection doesn’t really care about survival.”

And, a 2010 paper by Alan R. Templeton preemptively discarded Attenborough’s theory that physical evolution has been replaced by cultural evolution, arguing instead that “all organisms adapt to their environment, and humans are no exception. Culture defines much of the human environment, so cultural evolution has actually led to adaptive evolution in humans.”

Templeton gives the example of how technological advances in transportation have facilitated a rapid mixing of the human gene pool across the globe, resulting in the waning of differences between different populations with overall beneficial effects to human health.

Human evolution is now ‘100 times faster’

In their 2009 book The 10,000 Year Explosion: How Civilization Accelerated Human Evolution , Gregory Cochran and Henry Harpending calculate that — rather than there having been no biological change in humans over the past 50,000 years — human evolution has accelerated in the past 10,000 years.

Rather than slowing or stopping, the authors argue that evolution is now happening approximately “100 times faster than its long-term average over the 6 million years of our existence.”

Modern technology also presents us with opportunities to observe changes in humans at a molecular level. Scott Solomon , a biologist from the University of Texas in Austin, highlights in his book Future Humans: Inside the Science of Our Continuing Evolution that since 2000 — when Gould declared human evolution to have slowed or stopped — it has been possible to sequence the human genome.

In the 18 years since then, it has become much faster and cheaper to do so, providing scientists with an unprecedented insight into our recent evolutionary past.

From these data, Solomon explains, researchers have found evidence of natural selection altering genes responsible for our:

• tolerance of dietary changes
• protection from infectious changes
• ability to withstand ultraviolet radiation from sunlight
• ability to thrive in mountainous regions with decreased oxygen

The milk revolution

One easy-to-understand example of how humans have evolved over recent centuries is how, on some continents, our bodies have adapted to tolerate the most abundant food sources common to that region.

Around 11,000 years ago , for instance, adult humans were unable to digest lactose — the sugar in milk.

As humans in some regions began to rely on dairy farming as a source of nourishment, our bodies adjusted over time to be more able to digest this food, which, previously, was only tolerated by infants and toddlers.

We can see evidence of this evolution today because humans in areas with a long tradition of dairy farming — such as Europe — are much more tolerant of lactose in their diet than people in regions that do not have a heritage of dairy farming — such as Asia. Around 5 percent of people descended from Northern Europeans are lactose intolerant , compared with more than 90 percent of people of East Asian descent.

The Framingham Heart Study

Another source of evidence for recent human evolution cited by biologists is the Framingham Heart Study — the longest-running multigenerational medical study in the world.

Framingham is a small town in Massachusetts, and in 1948, a study of the town’s female population began; scientists wanted to understand what causes heart disease . The Framingham Heart Study is ongoing, and it has become an important repository for scientific data, not only relating to heart disease but also on changing trends in human health overall.

Scientists say that the Framingham data demonstrate that natural selection influenced the Framingham population — reducing height, increasing weight, lowering cholesterol levels, and lowering systolic blood pressures.

Importantly, the data do not show that average weight is increasing in Framingham because the women in the study are eating more. Instead, people with genes that affect these traits tend to have more children, meaning that these traits will become more common with subsequent generations.

“We see rapid evolution when there’s rapid environmental change, and the biggest part of our environment is culture, and culture is exploding,” Dr. Pardis Sabeti , a geneticist at Harvard University in Cambridge, MA, told the BBC.

“ That’s […] the take-home message of the Framingham study, that we are continuing to evolve, that biology is going to change with the culture, and it’s just a matter of not being able to see it because we’re stuck right in the middle of the process right now.” Dr. Pardis Sabeti

Why are the Dutch so tall?

A 2015 study published in Proceedings of The Royal Society B asked the question, “Does natural selection favor taller stature among the tallest people on Earth?” The researchers behind the study tested this by looking at the tallest people on Earth: the Dutch.

But the Dutch were not always the tallest people on Earth. The researchers observe that in the mid-18th century, the average height of Dutch soldiers was 165 centimeters, which was well below the average of soldiers from other European countries and tiny compared with American soldiers, who were 5–8 centimeters taller than the average Dutch soldier.

But Dutch men have experienced a relatively sudden growth spurt, adding an extra 20 centimeters to their average height over the past 150 years.

During the same period, American men have only added 6 centimeters to their average height, and men from other European countries have struggled to keep pace with their neighbors from the Netherlands.

But why? The authors took into account disparities between the Netherlands and the United States in diet, social inequality, and the availability and quality of healthcare, but they concluded that it was natural selection that was driving up the height of the Dutch.

Put simply, Dutch women were more likely to find tall men attractive and were therefore more likely to have children with them. Tall Dutch men, the study confirmed, have more children than shorter Dutch men.

And, although the study found that tall Dutch women were less likely to have children than middling-height Dutch women, the tall women who did have children had more children than their shorter countryfolk.

In combination, these preferences exert a powerful natural selection effect on the average height of people in the Netherlands.

While this might not exactly be Marvel Cinematic Universe levels of genetic mutation — we are sad to report that we did not find any studies suggesting that the human race is about to acquire a telepathy gene — these examples illustrate how evolution works in terms of modern humans.

Evolution is persistent, everywhere, pushing our species forward in tiny increments. It might even be occurring with an accelerated regularity.

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Article Contents

Foundations of evolutionary biology, adaptation, chance, and history, applications that affect our lives, meeting society's needs, contributions in biology and beyond, advancing human understanding.

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Evolution and Today's Society

Professor of Plant Biology in the Institute of Environmental and Evolutionary Biology, University of St. Andrews, St. Andrews, Fife KY16 9TH, Scotland. E-mail: [email protected]

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Thomas R. Meagher, Evolution and Today's Society, BioScience , Volume 49, Issue 11, November 1999, Pages 923–925, https://doi.org/10.2307/1313651

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There is a dynamic tension in the perception of evolution in the United States. On the one hand, the scientific community holds evolution to be a central unifying principle of biology, with sufficient supporting evidence that evolution is regarded as scientific fact. On the other hand, there is a lingering public view that the process of evolution, both in contemporary and historical biological populations, is controversial. This dichotomy has been brought into stark focus in recent months, as an issue of Science (25 June 1999) featured major scientific advances in evolution and the Kansas Board of Education decided (in August 1999) to no longer require evolution as part of their school curriculum. Such contrasts underscore a significant challenge in terms of communicating science to the public. The importance of this challenge is emphasized in the recent NAS report, Teaching about Evolution and the Nature of Science (1998, National Academy Press, Washington, DC), a key recommendation of which is that evolution is essential to school curricula if students—the public of the future—are to understand biology.

In fact, a clear understanding of evolutionary biology is essential for professionals in all biological fields if they are to push ahead the frontiers of their disciplines. Current research initiatives to deepen knowledge of the genetic basis of complex characters, recent advances in developmental morphology, and attempts to generate a comprehensive phylogenetic tree of life all draw heavily on evolutionary insights. Evolutionary biology is also contributing to ongoing advances in the study of human origins and behavior. Finally, there has been a long-term interplay between evolutionary theory and nonbiological fields such as statistics, economics, and computation.

In addition to its centrality in biology and its contributions to basic science, evolutionary biology addresses a wide array of current and emerging societal needs, ranging from biomedical applications to conservation efforts. For example, it provides a solid scientific framework for understanding the emergence of antibiotic resistance in pathogenic bacteria and for analyzing the emergence and epidemiology of novel diseases, such as HIV. Evolutionary biology also provides a scientific basis for policy decisions concerning the conservation of rare and endangered species, the adaptive implications of invasive species or new genetic varieties (including genetically engineered organisms), and the genetic responses to human perturbation of the environment.

So that an informed public can recognize connections between scientific advances and pressing societal needs, it is critical that evolutionary biologists communicate important scientific advances, ongoing research, and the nature of the scientific enterprise to the public as well as to scientists outside of their immediate discipline. In so doing, the foundations are laid for better public understanding of science as well as a stronger policy base for support of science itself.

To promote awareness of the contributions of evolutionary biology, representatives from eight scientific societies (the American Society of Naturalists, the Society for the Study of Evolution, the Society for Molecular Biology and Evolution, the Ecological Society of America, the Society of Systematic Biologists, the Genetics Society of America, the Animal Behavior Society, and the Paleonto-logical Society) met in April 1995 to discuss the need for a white paper on behalf of the scientific field of evolutionary biology. Co-chairs Douglas J. Futuyma and Thomas R. Meagher were elected to seek funding for the project and to coordinate and oversee writing and publication of the white paper. With support from the Alfred P. Sloan Foundation and the National Science Foundation, a working group of 17 scientists drawn from a broad geographic and institutional base and representing major disciplines in evolutionary biology was convened to draft the document. The existence of this working group and its charge were announced in The American Naturalist, Ecology, Evolution, Genetics, Molecular Biology and Evolution , and Science , and a Web site was established to enable the input of the broader scientific community.

The resulting documents—a report entitled Evolution, Science, and Society: Evolutionary Biology and the National Research Agenda and an executive summary of that report—are addressed to government agencies, private foundations, college and university administrations, corporations, scientific and educational societies, science educators on all levels, and the scientific community itself. They are also addressed to anyone interested in understanding the current and potential accomplishments of evolutionary biology.

The documents were written with the following major goals:

to describe our present understanding of evolution and the major intellectual accomplishments of evolutionary biology;

to identify major questions and challenges in which progress in evolutionary science can be expected in the near future;

to describe past and expected contributions of evolutionary biology, both to other sciences and to societal needs in areas such as health, agriculture, and the environment; and

to suggest ways in which progress can be facilitated in basic research, in applications of evolutionary biology to social needs, and in biological science education.

Both versions of Evolution, Science, and Society —the executive summary and the more detailed executive document—are currently available in either a printed form (from the author) or on the Web ( www.amnat.org ).

The executive summary is reproduced on the following pages. Our goal in publishing the executive summary in BioScience is to ensure that Evolution, Science, and Society is widely accessible, as well as available in a form that can be readily cited in the scientific literature and elsewhere. In addition, it is replicated here to assist those who are interested in promoting broader public understanding of science. In a similar vein, the more detailed version will be published as a supplement to The American Naturalist in 2000. It is the intention of the Evolution, Science, and Society working group that this report be reproduced and used in a variety of contexts supporting research and education in evolution.

Futuyma DJ. 1995. The uses of evolutionary biology. Science 267: 41-42.

Meagher LR, Meagher TR, eds. 1994. Leaping into the Future with Evolutionary Biology: The Emerging Relevance of Evolutionary Biology Applied to Problems and Opportunities . New Brunswick (NJ): Rutgers University Press.

National Academy of Sciences, Working Group on Teaching Evolution. 1998. Teaching about Evolution and the Nature of Science . Washington (DC): National Academy Press.

President's Committee of Advisors on Science and Technology. 1998. Teaming with Life: Investing in Science to Understand and Use Americas Living Capital . Washington (DC): PCAST.

Systematics Agenda 2000. 1994. Systematics Agenda 2000: Charting the Biosphere . New York:, Department of Ornithology, American Museum of Natural History.

Evolutionary biology is the study of the history of life and the processes that lead to its diversity. Based on principles of adaptation, chance, and history, evolutionary biology seeks to explain all the characteristics of organisms, and, therefore, occupies a central position in the biological sciences.

R elevance of E volutionary B iology to the N ational R esearch A genda

The twenty-first century will be the “Century of Biology.” Driven by a convergence of accelerating public concerns, the biological sciences will be increasingly called on to address issues vital to our future well-being: threats to environmental quality, food production needs due to population pressures, new dangers to human health prompted by the emergence of antibiotic resistance and novel diseases, and the explosion of new technologies in biotechnology and computation. Evolutionary biology in particular is poised to make very significant contributions. It will contribute direcly to pressing societal challenges as well as inform and accelerate other biological disciplines.

Evolutionary biology has unequivocally established that all organisms evolved from a common ancestor over the last 3.5 billion years; it has documented many specific events in evolutionary history; and it has developed a well-validated theory of the genetic, developmental, and ecological mechanisms of evolutionary change. The methods, concepts, and perspectives of evolutionary biology have made and will continue to make important contributions to other biological disciplines, such as molecular and developmental biology, physiology, and ecology, as well as to other basic sciences, such as psychology, anthropology, and computer science.

In order for evolutionary biology to realize its full potential, biologists must integrate the methods and results of evolutionary research with those of other disciplines both within and outside of biology. We must apply evolutionary research to societal problems, and we must include the implications of that research in the education of a scientifically informed citizenry.

To further such goals, delegates from eight major professional scientific societies in the United States, whose subject matter includes evolution, have prepared this document. It includes contributions by other specialists in various areas. Feedback on earlier drafts was elicited from the community of evolutionary biologists in the United States, and the draft was made public on the World Wide Web. The delegates arrived at a series of recommendations that address the areas that follow.

A dvancing U nderstanding through R esearch

To capitalize on evolutionary biology as an organizing and integrating principle, we urge that:

▪ evolutionary perspectives be incorporated as a foundation for interdisciplinary research to address complex scientific problems

▪ evolutionary biologists work toward building meaningful links between basic research and practical application

▪ evolutionary biology play a more explicit role in the overall mission of federal agencies that could benefit from contributions made by this field

A dvancing U nderstanding through E ducation

We encourage major efforts to strengthen curricula in primary and secondary schools, as well as in colleges and universities, including:

▪ support of supplemental training for primary school teachers and/or midcareer training for secondary school science teachers in evolutionary biology

▪ greater emphasis on evolution in undergraduate college curricula for biology majors and premedical students, with accessible alternative courses for nonmajors

▪ integration of relevant evolutionary concepts into the postbaccalaureate training of all biologists and of professionals in areas such as medicine, law, agriculture, and environmental sciences

A dvancing U nderstanding through C ommunication

We urge the following roles for evolutionary biologists:

▪ communicating to federal agencies, and to other institutions that support basic or applied research, the relevance of evolutionary biology to the missions of these organizations

▪ training the next generation of evolutionary biologists to be aware of the relevance of their field to societal needs

▪ informing the public about the nature, progress, and implications of evolutionary biology

W hat D oes the F uture H old for E volutionary B iology ?

Researchers in molecular and developmental biology, physiology, ecology, animal behavior, psychology, anthropology, and other disciplines continue to adopt the methods, principles, and concepts of evolutionary biology as a framework. Likewise, applied research in forestry, agriculture, fisheries, human genetics, medicine, and other areas has increasingly attracted scientists trained in evolutionary biology. Evolutionary biologists have expanded their vision, addressing both basic questions throughout the biological disciplines and problems posed by society's needs. As a result of both the rapid growth of this “evolutionary work force” and technological advances in areas such as molecular methodology, computing, and information processing, progress in evolutionary biology and related areas is more rapid now than ever before. With appropriate and necessary support in education and research, the evolutionary disciplines will make ever greater contributions to applied and basic knowledge.

Applied Science

In the applied realm, evolutionary biologists are embracing their social responsibilities. There are many ways in which their scientific efforts can help humanity:

▪ to understand and combat genetic, systemic, and infectious diseases

▪ to understand human physiological adaptations to stresses, pathogens, and other causes of ill health

▪ to improve crops and mitigate damage by pathogens, insects, and weeds

▪ to develop tools for analyzing human genetic diversity as it applies to health, law, and the understanding of human behavior

▪ to use and develop biological resources in a responsible manner

▪ to remedy damage to the environment

▪ to predict the consequences of global and regional environmental change

▪ to conserve biodiversity and discover its uses

Basic Science

In basic science, we stand at the threshold of:

▪ fully documenting biodiversity and describing the phylogenetic relationships among ail organisms

▪ more completely understanding the causes of major changes in the history of life

▪ discovering and explaining processes of evolution at the molecular level

▪ understanding how developmental mechanisms evolve and give rise to new anatomical structures

▪ elucidating the processes that both cause and constrain adaptations in physiology, endocrinology, and anatomy

▪ deriving a deeper understanding of the adaptive meaning and mechanisms of behavior

▪ developing a predictive theory of coevolution among species, such as pathogens, parasites, and their hosts, and of the effects of coevolution on populations and ecological communities

C onclusion

Evolutionary biology plays a central role in the complexity of biological systems. Evolution is the source of biocomplexity. The continued and enhanced support of this field is critical to maximizing the nation's research progress in both basic and applied arenas. In terms of societal needs for the twenty-first century, the time to make the investment in evolutionary biology is now, while there is still time either to change current trends or to better prepare us to deal with their consequences. Current and projected population levels will result in increasing environmental impacts, increasing pressure on food production, ever greater challenges to biological diversity, and enhanced opportunities for the emergence of new diseases. A healthy scientific base in evolutionary biology is an essential element in preparing us to address these issues. Evolutionary biology must be at the heart of the nation's research agenda in biology, just as it is at the heart of the field of biology.

Universal phylogenetic tree showing the relationships among Bacteria (e.g. most bacteria and blue-green algae), Archaea (e.g. methanogens and halophiles) and Eucarya (e.g. protists, plants, animals, and fungi).

Deane Bowers, University of Colorado-Boulder. Baltimore Checkerspot butterfly (Euphydryas phaeton) , Eastern United States

Julie Margaret Cameron, c/o Clements Museum, University of Michigan. Carte de visite photograph of Charles Darwin (1874)

Bruce Baldwin, University of California–Berkeley. Mauna Kea silversword (Argyroxiphium sandwicense subsp. sandwicense ), Wailuku drainage, Hawaii

R. Kellogg, c/o Annalisa Berta, San Diego State University. Line drawing of archaeocete (fossil whale) skeleton. Abstracted with permission from A. Berta, 1994. What Is a Whale? Science 263:180. © 1994, American Association for the Advancement of Science

H. Douglas Pratt, c/o Lenny Freed, University of Hawaii. Hawaiian honeycreeper bill variation

Aravinda Chakravarti, Case Western Reserve University. Gradient of distribution in Europe of the major mutation causing cystic fibrosis relative to overall cf genes

Karl Ammann, c/o NOAHS Center, National Zoological Park. Cheetah

Charles W. Myers, American Museum of Natural History. Poison-dart frog (Phyllobates terribilis) , Colombia, South America

Charles Rick, University of California-Davis. Cultivated tomato and its wild relatives

Sean B. Carroll, University of Wisconsin. Hox gene organization and expression in Drosophila and mouse embryos. Reproduced with permission from S.B. Carroll et al., 1995. Homeotic genes and the evolution of arthropods and chordates. Nature 376: 479–485. © 1995, Macmillan Magazines Ltd.

David Maddison, University of Arizona. Tree of Life logo

National Museum of Kenya, c/o Craig S. Feibel, Rutgers University. 1.9-million-year-old hominid skull (Homo habilis) , Koobi Fora, Rift Valley, Africa

African mask, Rutgers University photo archives

Norman R. Pace, University of California–Berkeley. Universal phylogenetic tree based on ribosomal RNA sequence differences. Abstracted with permission from N.R. Pace, 1997. A Molecular View of Microbial Diversity and the Biosphere. Science 276: 734–740. © 1997, American Association for the Advancement of Science

John Weinstein, Field Museum of Natural History, and David Jablonski, University of Chicago. Fossil crinoids, Cretaceous Period (85 million years old), Kansas. Negative GE085594c

EVOLUTION BY NATURAL SELECTION . Nineteenth-century biologists Charles Darwin and Alfred Russell Wallace established the foundations for evolutionary theory.

PHYLOGENETIC ANALYSIS . Recent advances in DNA sequencing and computation permit precise reconstruction of evolutionary relationships among species. For example, molecular data have enabled deeper understanding of the evolutionary origins of the local species of the silverswords, a group of plants endemic to Hawaii.

MORPHOLOGICAL AND MOLECULAR VARIATION . Variation is a key feature of evolution. Differentiation in bill form among related species of honeycreepers provides insight into evolutionary adaptation for feeding. Molecular variation provides insight into genetic processes underlying evolutionary change.

THE FOSSIL RECORD . Fossils provide dues about the evolutionary origins of adaptations. Intermediate, or transitional, forms in the fossil record have shown that whales and other cetaceans evolved from land-dwelling ancestors.

W hat I s E volution ?

Biological evolution consists of change in the hereditary characteristics of groups of organisms over the course of generations. From a long-term perspective, evolution is the descent with modification of different lineages from common ancestors. From a short-term perspective, evolution is the ongoing adaptation of organisms to environmental challenges and changes. Thus evolution has two major components: the branching of lineages and changes within lineages.

W hat A re the G oals of E volutionary B iology ?

Evolutionary biology seeks to explain the diversity of life: the variety of organisms and their characteristics, and their changes over time. Evolutionary biology also seeks to interpret and understand organismal adaptation to environmental conditions. The two encompassing goals of evolutionary biology are to discover the history of life on earth and to understand the causal processes of evolution. Insights achieved through efforts to meet these goals greatly enhance our understanding of biological systems.

Evolutionary biologists often work at the interface of many subdisciplines of biology, leading to the development of subject areas such as behavioral evolution, evolutionary developmental biology, evolutionary ecology, evolutionary genetics, evolutionary morphology, evolutionary systematics, and molecular evolution. The subdisciplines of evolutionary biology also have formed direct links with fields such as statistics, economics, geology, anthropology, and psychology.

H ow I s E volution S tudied ?

Evolutionary biology draws on a wide range of methodologies and conceptual approaches.

Methods for understanding the history of evolution include observations of the fossil record and categorization and classification of variations among living organisms. Differences and similarities among species in anatomy, genes, and other features can be analyzed by molecular and statistical methods that enable us to estimate historical relationships among species and the sequence in which their characteristics evolved.

Studies of ongoing evolutionary change employ observation and experimentation. Analysis of genetic variation enables us to characterize mutation, genetic drift, natural selection, and other processes of evolution. The “comparative method” contrasts features of species that have adapted to different environments. Sophisticated mathematical models and analyses are frequently employed for both description and predication.

W hy I s E volutionary B iology I mportant ?

Evolutionary biology provides the key to understanding the principles governing the origin and extinction of species. It provides causal explanations, based on history and on processes of genetic change and adaptation, for the full sweep of biological phenomena, ranging from the molecular to the ecological. Thus, evolutionary biology allows us to determine not only how and why organisms have become the way they are, but also what processes are currently acting to modify or change them.

Response to change is a feature of evolution that is becoming increasingly important in terms of scientific input into societal issues. We live in a world that is undergoing constant change on many levels, and much of that change is a direct consequence of human activity. Evolutionary biology can contribute explicitly to enhanced awareness and prediction of mid- and long-term consequences of environmental disturbances, whether they be deforestation, application of pesticides, or global warming.

Distinctive perspectives on biology offered by evolutionary biology include emphasis on the interplay between chance and adaptation as conflicting agents of biological change, on variation as an inherent feature of biological systems, and on the importance of biological diversity. Variation is a key concept, since evolutionary change ultimately depends on the differential success of competing genetic lineages. The ultimate consequence of variation and evolutionary divergence is biological diversity.

Biological species are not fixed entities, but rather are subject to ongoing modification through chance or adaptation. Understanding why and how some species are able to change apace with new environmental challenges is critical to the sustainability of human endeavor.

EVOLUTION OF HUMAN GENETIC DISORDERS . Some genetic diseases, such as cystic fibrosis, are caused by mutations that occur at high frequencies in certain human populations in Europe. Evolutionary geneticists are working to understand how natural selection keeps deleterious genes at such high frequencies. Their findings may lend insight to the broader physiological impacts of the cystic fibrosis gene.

CONSERVATION GENETICS . Evolutionary analysis reveals extremely low levels of genetic diversity among living cheetah, likely due to a dramatic population decline—and associated inbreeding—thousands of years ago. This hinders the cheetah's ability to reproduce successfully, which threatens the species' survival. Such information is being used to develop management recommendations for this endangered species.

NATURAL PRODUCTS FROM POISON FROGS . Knowledge of evolutionary relationships has helped to guide research scientists to the discovery of new natural compounds from Central and South American poison frogs. Potential biomedical applications include heart-stimulating activity and use in painkillers.

GENETIC RESOURCES FOR CROP IMPROVEMENT . Evolutionary relationships between crops and wild relatives provide insight into potentially useful genes for crop improvement.

H ow D oes E volutionary B iology C ontribute to S ociety ?

In addition to the historical dimension, evolution is an important feature in our everyday lives. Evolution is happening all around us: in our digestive tracts, in our lawns, in woodland lots, in ponds and streams, in agricultural fields, and in hospitals. For shortlived organisms such as bacteria and insects, evolution can happen on a very short time scale. This immediacy brings evolutionary biology directly into the applied realm. Indeed, evolutionary biology has a long history and a bright future in terms of its ability to address pressing societal needs. Evolutionary biology has already made particularly strong contributions in the following areas:

Environment and conservation . Evolutionary insights are important in both conservation and management of renewable resources. Population genetic methods are frequently used to assess the genetic structure of rare or endangered species as a means of determining appropriate conservation measures. Studies of the genetic composition of wild relatives of crop species can be used to discover potentially useful new genes that might be transferred into cultivated species. Studies of wild plants' adaptations to polluted or degraded soils contribute to the reclamation of damaged land.

Agriculture and natural resources . The principles of plant and animal breeding strongly parallel natural evolutionary mechanisms, and there is a rich history of interplay between evolutionary biology and agricultural science. Evolutionary insights play a clear role in understanding the ongoing evolution of various crop pathogens and insect pests, including the evolution of resistance to pest-control measures. The methods of evolutionary genetics can be used to identify different gene pools of commercially important fish and other organisms, their migration routes, and differences in their physiology, growth, and reproduction.

Finding useful natural products . Many thousands of natural products are used in medicine, food production and processing, cosmetics, biotechnology, pest control, and industry, but millions of other potentially useful natural products have yet to be screened or even discovered. Evolutionary principles allow a targeted search by predicting adaptations to environmental selection pressures and by identifying organisms related to those that have already yielded useful natural products. Exploration of related species also has made it possible to develop natural products from more accessible relatives of rare species in which natural products have been found, as occurred when the rare and endangered Pacific yew was found to contain a substance that led to development of a drug (tamoxifen) useful in treating breast cancer.

Human health and medicine . Methods and principles from evolutionary biology have contributed to understanding the links between genes and human genetic diseases, such as cystic fibrosis. Evolutionary methods help to trace the origins and epidemiology of infectious diseases, and to analyze the evolution of antibiotic resistance in pathogenic microorganisms. Evolutionary principles are used to interpret human physiological functions and dietary needs. Methods developed by evolutionary geneticists are playing an important role in mapping defective human genes, in genetic counseling, and in identifying genetic variants that alter risks for common systemic diseases and responses to medical treatments.

Biotechnology . The interplay between biotechnology and evolutionary biology holds great promise for application to important societal needs. As genetic engineering has reached the field implementation stage, evolutionary biologists have been prominently involved in risk assessment as well as interpretation of phenotypic consequences of trans-gene insertion. Finally, the automation of DNA sequencing has made it possible to reconstruct the precise genealogical relationship among specific genes, such as those of the human immunodeficiency virus (HIV).

Understanding humanity . Evolutionary biology has contributed greatly to human understanding of ourselves by describing our origins, our relationships to other living things, and the history and significance of variation within and among different groups of people. Evolutionary anthropologists, psychologists, and biologists have advanced hypotheses on the biological bases of human culture and behavior. In addition, the evolutionary framework for understanding humanity has had a profound impact on literature, the arts, philosophy, and other areas of the humanities.

DEVELOPMENTAL BIOLOGY . Recent studies of many different types of animals suggest that much of animal diversity has evolved by changes in a common set of regulatory genes. The organization of such regulatory genes has been studied in detail in model organisms, such as fruit flies, and parallel genetic effects have been identified in a wide range of organisms.

THE TREE OF LIFE . Advances in molecular, morphological, and computational approaches have enabled the emergence of a comprehensive framework for the evolutionary history of all life on earth. The Tree of Life project provides a unified network for systematic investigation on all levels.

HUMAN ORIGINS . Studies of variation in modern populations, recent analysis of DNA extracted from fossil remnants, and an ever more complete fossil record have provided deeper insight into the evolutionary emergence of modern humans and their culture.

H ow D oes E volutionary B iology C ontribute to B asic S cience ?

Evolutionary biology has far-reaching scientific impact. Among their accomplishments in studying the history and processes of evolution, evolutionary biologists have:

▪ established that all organisms have evolved from a common ancestor over more than 3.5 billion years of earth's history

▪ developed methods of inferring phylogenetic, or genealogical, relationships among organisms

▪ described patterns of diversification and extinction in both the fossil record and contemporary ecosystems

▪ developed and tested general theories that account for the evolution of phenotypic traits, including complex characters such as cooperative behavior and senescence

▪ made substantial progress in understanding evolution at the molecular level

▪ elucidated many aspects of human evolution

Contributions to Other Biological Disciplines

Evolution is central to biological understanding. Biologists in diverse fields regard at least a portion of what they do as evolutionary. Recent accomplishments to which evolutionary biology has contributed include the following:

Molecular biology . Evolutionary approaches have contributed insight into the function and structure of molecular processes within cells. Examples include reconstruction and functional analysis of ancestral protein sequences, and elucidation of the significance of different types of DNA. Evolutionary research thus points the way to research on fundamental molecular mechanisms.

Developmental biology . A resurgence in interaction between developmental biology and evolutionary biology is now under way, in part through comparisons among families of genes that play critical roles in development. For example, the same genes in organisms as different as insects and mammals play surprisingly similar developmental roles in some instances, and different roles in other cases. Such studies help to identify the developmental functions of genes and lead to a deeper understanding of the processes that transform a fertilized egg into a complex adult.

Physiology and anatomy . Evolutionary biology has long influenced the study of physiology and anatomy in animals and plants, and has the potential to make many other contributions that only now are being developed. Some of these contributions will affect the study of human physiology, including related areas such as clinical psychology. The logical perspectives, methods, and comparative data of evolutionary biology can advance our understanding of functional anatomy and physiological mechanisms, and can be applied to areas such as medicine, agriculture, and veterinary science.

Neurobiology and behavior . From its inception, the field of animal behavior has had a strong evolutionary base, for its goals have included understanding the evolutionary origin of behavioral traits and their adaptiveness. The evolutionary study of animal behavior has joined with comparative psychology in several areas of research, such as the study of learning and the search for adaptive mechanisms in human cognitive processes.

Applications beyond biology . There have long been rewarding interactions between evolutionary biology and other analytical fields, notably statistics and economics. Some of the basic tools in statistics, including analysis of variance and path analysis, were originally developed by evolutionary biologists. Along the same lines, evolutionary algorithms that mimic natural selection in biological systems are currently being used in computer and systems applications.

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