Who We Are and How We Got Here: Ancient DNA and the New Science of the Human Past

by David Reich

the few major new claims that Cavalli-Sforza did make have essentially all been proven wrong.

first farmers even in the most remote reaches of Europe—Britain, Scandinavia, and Iberia—had very little hunter-gatherer-related ancestry. In fact, they had less hunter-gatherer ancestry than is present in diverse European populations today.

the lower genetic diversity of non-Africans compared to Africans reflects the reduced diversity of the modern human population that expanded out of Africa and the Near East after around fifty thousand years ago. But the present-day structure of human populations cannot recover the fine details of ancient events. The problem is not just that people have mixed with their neighbors, blurring the genetic signatures of past events. It is actually far more difficult, in that we now know, from ancient DNA, that the people who live in a particular place today almost never exclusively descend from the people who lived in the same place far in the past.9

the people who live in a particular place today almost never exclusively descend from the people who lived in the same place far in the past.9

Much of the technology for the genome-wide ancient DNA revolution was invented by Svante Pääbo and his colleagues at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, who developed it to study extremely old samples such as archaic Neanderthals and Denisovans.

My partner in this effort has been Nadin Rohland, who did her own seven-year apprenticeship in Pääbo’s laboratory before she came to mine.

Rohland and I realized that a technique developed by Matthias Meyer and Qiaomei Fu in Pääbo’s laboratory could be the key to the industrial-scale study of ancient DNA.

scale study of ancient DNA. Meyer and Fu’s invention was born of necessity: the need to extract DNA from an approximately forty-thousand-year-old early modern human from Tianyuan Cave in China.16 When

techniques invented for printing electronic circuits to attach

We automated the whole approach, processing the DNA using robots that allowed a single person to study more than ninety samples at once in the span of a few days. We hired a team of technicians to grind powder out of ancient remains, to extract DNA from the powder, and then to turn the extracted DNA into a form that we could sequence. The laboratory work was only the beginning.

We discovered that the population of northern Europe was largely replaced by a mass migration from the eastern European steppe after five thousand years ago18;

human genome variation has surpassed the traditional toolkit of archaeology—the study of the artifacts left behind by past societies—in what it can reveal of changes in human populations in the deep past.22

great surprise that emerges from the genome revolution is that in the relatively recent past, human populations were just as different from each other as they are today, but that the fault lines across populations were almost unrecognizably different from today. DNA extracted from remains of people who lived, say, ten thousand years ago shows that the structure of human populations at that time was qualitatively different.

11, “The Genomics of Race and Identity,” argues that the orthodoxy that has emerged over the last century—the idea that human populations are all too closely related to each other for there to be substantial average biological differences among them—is no longer sustainable, while also showing that racist pictures of the world that have long been offered as alternatives are even more in conflict with the lessons of the genetic data.

We scientists are conditioned by the system of research funding to justify what we do in terms of practical application to health or technology. But shouldn’t intrinsic curiosity be valued for itself? Shouldn’t fundamental inquiry into who we are be the pinnacle of what we as a species hope to achieve? Isn’t an attribute of an enlightened society that it values intellectual activity that may not have immediate economic or other practical impact? The study of the human past—as of art, music, literature, or cosmology—is vital because it makes us aware of aspects of our common condition that are profoundly important and that we heretofore never imagined.

“Mitochondrial Eve,” lived sometime after 200,000 years ago.3 The best current estimate is around 160,000 years ago, although it is important to realize that like most genetic dates, this one is imprecise because of uncertainty about the true rate at which human mutations occur.4

Archaeological evidence of stone tool types also points to a great change after around fifty thousand years ago, a period known to archaeologists of West Eurasia as the Upper Paleolithic, and to archaeologists of Africa as the Later Stone Age.

Richard Klein. He put forward the idea that the Later Stone Age revolution of Africa and the Upper Paleolithic revolution of western Eurasia, when recognizably modern human behavior burst into full flower after about fifty thousand years ago, were driven by the rise in frequency of a single mutation of a gene affecting the biology of the brain, which permitted the manufacture of innovative tools and the development of complex behavior.

The intensification of evidence for modern human behavior after fifty thousand years ago is undeniable, and raises the question of whether biological change contributed to it.

Svante Pääbo, who arrived in Allan Wilson’s laboratory just after the “Mitochondrial

engineered mice with the human versions of FOXP2 are identical to regular mice in most respects, but squeak differently, consistent with the idea that these changes affect the formation of sounds.14 These two mutations at FOXP2 cannot have contributed to the changes after fifty thousand years ago, since Neanderthals shared them,15 but Pääbo and his colleagues later identified a third mutation that is found in almost all present-day humans and that affects when and in what cells FOXP2 gets turned into protein. This change is absent in Neanderthals, and thus is a candidate for contributing to the evolution of modern humans after their separation from Neanderthals hundreds of thousands of years ago.16

Roger Lewin in 1987 dubbed the common maternal ancestor of all people living today “Mitochondrial Eve,” he evoked a creation story—that of a woman who was the mother of us all, and whose descendants dispersed throughout the earth.

one needs to realize that beyond mitochondrial DNA, the genome is not one continuous sequence from a single ancestor but is instead a mosaic.

Females create an average of about forty-five new splices when producing eggs, while males create about twenty-six splices when producing sperm, for a total of about seventy-one new splices per generation.20 So it is that as we trace each generation back further into the past, a person’s genome is derived from an ever-increasing number of spliced-together ancestral fragments.

Twenty generations in the past, the number of ancestors is almost a thousand times greater than the number of ancestral stretches of DNA in a person’s genome, so it is a certainty that each person has not inherited any DNA from the great majority of his or her actual ancestors. These calculations mean that a person’s genealogy, as reconstructed from historical records, is not the same as his or her genetic inheritance.

In my mind’s eye, when I think of a genome, I view it not as a thing of the present, but as deeply rooted in time, a tapestry of threads consisting of lines of descent and DNA sequences copied from parent to child winding back into the distant past.

and Eurasia, are no longer tenable. In 2016, my colleagues and I used an adaptation of the Li and Durbin method26 to compare populations from around the world to the earliest branching modern human lineage that has contributed a large proportion of the ancestry of a population living today: the one that contributed the lion’s share of ancestry to the San hunter-gatherers of southern Africa. Our study,27 like most others,28 found that the separation had begun by around two hundred thousand years ago

implying

Li and Durbin method

As genome-wide association studies proceed, they are beginning to investigate human variation in cognitive and behavioral traits,39 and studies like these—such as the ones for height—will make it possible to explore whether the shift to behavioral modernity among our ancestors was driven by natural selection.

If we search for answers in a small number of mutations that arose shortly before the time of the Upper Paleolithic and Later Stone Age transitions, we are unlikely to find satisfying explanations of who we are.

But until around forty thousand years ago, the world was inhabited by multiple groups of archaic humans who differed from us physically but walked upright and shared many of our capabilities. The question that the archaeological record cannot answer—but the DNA record can—is how those archaic people were related to us.

Both Neanderthals and anatomically modern humans made stone tools using a technique that has become known as Levallois, which requires as much cognitive skill and dexterity as the Upper Paleolithic and Later Stone Age toolmaking techniques that emerged among modern humans after around fifty thousand years ago. In this technique, flakes are struck off carefully prepared rock

is evident at Fumane in southern Italy where around forty-four thousand years ago, Neanderthal-type stone tools gave way to tools typical of modern humans. In southwestern Europe, tools typical of modern humans, made in a style called Châtelperronian, have been found amidst Neanderthal remains that date to between forty-four thousand and thirty-nine thousand years ago, suggesting that Neanderthals may have imitated modern human toolmaking, or that the two groups traded tools or materials. Not all archaeologists accept this interpretation, though, and there is ongoing debate about whether Châtelperronian artifacts were made by Neanderthals or by modern humans.

pressures, not shared ancestry. This is why archaeological and skeletal records cannot determine the relatedness of Neanderthals to us. Studies of the genome can.

Neanderthals shared maternal-line ancestors with modern humans more recently than previously thought13—the best current estimate is 470,000 to 360,000 years ago.14 Mitochondrial DNA analysis also confirmed that the Neanderthals were highly distinctive. Their DNA type was outside the range of present-day variation in humans, sharing a common ancestor with us at a date several times more ancient than the time when “Mitochondrial Eve” lived.15

The test we developed is now called the “Four Population Test,” and it has become a workhorse for comparing populations. The test takes as its input the DNA letters seen at the same position in four genomes: for example, two modern human genomes, the Neanderthal, and a chimpanzee. It examines whether, at positions where there is a mutation distinguishing the two modern human genomes that is also observed in the Neanderthal genome—which must reflect a mutation that occurred prior to the final separation of Neanderthals and modern humans—the Neanderthal matches the second human population at a different rate from the first. If the two modern humans descend from a common ancestral population that separated earlier from the ancestors of Neanderthals, there is no reason why the mutation is more likely to have been passed down one modern human line than another, and thus the rate of matching of each of

When we tested diverse present-day human populations, we found Neanderthals to be about equally close to Europeans, East Asians, and New Guineans, but closer to all non-Africans than to all sub-Saharan Africans, including populations as different as West Africans and San hunter-gatherers from southern Africa.

Rasmus Nielsen,

By measuring the typical sizes of the stretches of Neanderthal-related DNA in present humans, evident from the size of sequences that match the Neanderthal genome more than they do sub-Saharan African genomes, we can learn how many generations have passed since the Neanderthal DNA entered a modern person’s ancestors.

We now know that at least part of the explanation is dilution. Ancient DNA from Europeans who lived before nine thousand years ago shows that pre-farming Europeans had just as much Neanderthal ancestry as East Asians do today.26 The reduction in Neanderthal ancestry in present-day Europeans is due to the fact that they harbor some of their ancestry from a group of people who separated from all other non-Africans prior to the mixture with Neanderthals (the story of this early-splitting group revealed by ancient DNA is told in part II of this book).

The first place of reduced Neanderthal ancestry was on chromosome X, one of the two sex chromosomes. This reminded me of a pattern that Nick Patterson and I had run into in our work on the separation of human and chimpanzee ancestors in a study we had carried out together and published years before.33 There are only three copies of chromosome X in any population for every four other chromosomes (because females carry two copies and males only one, in contrast to two copies in each sex for most of the rest of the chromosomes).

more than fifty Eurasians spread over the last forty-five thousand years.41 We showed that Neanderthal ancestry decreased continually from 3 to 6 percent in most of the samples we analyzed from earlier times to its present-day value of around 2 percent at later times and that this was driven by widespread natural selection against Neanderthal DNA.

The new mitochondrial DNA from the Denisova finger bone featured nearly four hundred differences from the mitochondrial DNA of both present-day humans and Neanderthals. Based on the rate at which mutations accumulate, mitochondrial DNA sequences from present-day humans and Neanderthals are estimated to have separated from each other 470,000 to 360,000 years ago.3 The number of mutational differences found in the mitochondrial DNA from the Denisova finger bone suggested a separation time of roughly eight hundred thousand to one million years ago.

While Pääbo had screened dozens of Neanderthal samples to find a few with up to 4 percent primate DNA, this finger bone had about 70 percent.

australopithecenes,

Huxley’s Line, a natural boundary that separates New Guinea, Australia, and the Philippines from the western parts of Indonesia and the Asian mainland.

population of modern humans, Denisovans, and Neanderthals could both have arisen within Eurasia, without requiring two

Event One was the spread of modern humans into western Eurasia and is evident in the two most ancient samples,

Event Two was the spread of the lineage that gave rise to all later hunter-gatherers in Europe. Fu’s Four Population Tests showed that both an approximately thirty-seven-thousand-year-old individual from eastern Europe (present-day European Russia)23 and an approximately thirty-five-thousand-year-old individual from western Europe (present-day Belgium) were part of a population that contributed to all later Europeans, including today’s.24 Fu also used Four Population Tests to show that during the