The Invisible History of the Human Race

by Christine Kenneally

  The complex tales told by the ancient Siberian and Clovis children are echoed by what happened during the out-of-Africa exodus in the rest of the world. No matter where they stopped, even after a group of travelers settled in place, life—and the genome—kept changing. Some settlers were joined—or overrun—by others; sometimes a subgroup set off anew. It was thought that the Australian genome was isolated for tens of thousands of years before eighteenth-century colonization, but in 2013 it was discovered that roughly four thousand years ago a band from the Indian subcontinent traveled into Australia and contributed to the genome. Around the same time, there were changes in tools and in the way food was processed, and the dingo first appeared, suggesting that the Indian group may have brought the wild canine in with them.

  Of course, it’s not just the descendants of the out-of-Africa band who have changed; African populations have changed as well. Indeed, as far as the genome is concerned, the groups who remained were also small bands of travelers. There were genomic bottlenecks on the African continent long before the 60,000-year mark: In 2012 researchers announced that they had found one of the original branches of the human family tree. The Khoe-San, a tribe who live in southern Africa, split off from everyone else 100,000 years ago. In addition, many groups journeyed through the land and blended with other groups. In many parts of the continent native Africans effectively journeyed through different environments even as they stayed in the same place. In all that time the climate changed, plants bloomed, and animals thrived, and then ice ages dried the land out.

  Feldman and colleagues have counted the number of bottlenecks that different modern populations have passed through and have found that populations that have passed through the most bottlenecks have more deleterious mutations in their genome than populations that have passed through fewer. Yet even as they find ways to identify difference, their work still underlines the overwhelming commonality of all people. When you examine the human genome, Feldman told me, “The thing that strikes you is that people in different continents actually have very similar genomes and that the fraction of the genomes that are different is pretty small. I mean, you’re down to a tenth of a percent.”

  When humans left Africa 60,000 years ago, it was almost certainly not the first journey they had attempted but merely the most successful one. The bones of modern-looking humans found in the Skhul and Qafzeh caves in Israel date to 120,000 years ago. These people are not our direct ancestors but were likely an earlier group who walked out of Africa. It may be the case that the out-of-Africa journey that led to the peopling of the world was more complicated too. A 2014 study that compared both DNA and the shapes of fossilized human skulls suggests that the ancestors of the Australian Aboriginal population actually left Africa 130,000 years ago and that there were at least two waves of the modern human exodus from Africa. Stone tools found in the inland deserts and mountains of the Arabian peninsula that date to more than 100,000 years ago support this idea. Yet another kind of creature left Africa much earlier, almost 500,000 years ago, and founded a civilization that spread across much of the world.

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  There’s another way we can tell that the human tree splits between people who come from Africa and people born elsewhere in the world. The traces of the split lead us back to an event that occurred just as the out-of-Africa diaspora began. When the small band of travelers was essentially standing on the doorstep of the continent, perhaps wondering where to turn, they met up with a group of Neanderthals and ended up making some human-Neanderthal babies together. All non-Africans today carry the mark of those encounters in their DNA.

  In just the last few years we have learned that 85 percent of all people carry DNA from Neanderthals, an entirely different species that lived until 27,000 years ago. If the research on the human genome hasn’t completely destroyed the idea of genetic purity, our newly discovered Neanderthal ancestors show how truly absurd the notion is. Colin Groves, a professor of bioanthropology at the Australian National University, explained, “Neanderthals and Homo sapiens are like lions and tigers. Genetically they are sharply distinct, but they can interbreed.”

  A first-draft sequence of the Neanderthal genome was published in 2010 by an international team of scientists, including David Reich at Harvard. I visited Reich’s lab in 2011 and asked him what that first meeting between our ancestors was like. He explained that it might have been a meeting of a few dozen humans and Neanderthals, or it could have been a blending of thousands of individuals. At the time I spoke with Reich, we didn’t know which parts of the human genome had come to us from Neanderthals. Since then the science of Neanderthal DNA has progressed faster than anyone imagined it would.

  The boom in Neanderthal knowledge comes from a revolution in the science of ancient DNA, much of it led by Svante Pääbo from the Max Planck Institute in Leipzig, Germany. Ancient DNA is the most difficult kind of DNA to study. For a long time it was thought that DNA could not survive beyond days or weeks, yet scientists can now locate and extract DNA from fossils that could be tens of thousands of years old. The first Neanderthal genome was extracted from bones that were found in a cave in Croatia dating to more than 38,000 years ago. The technical challenges of reading ancient DNA are so complicated that it was thought to be simply impossible, a situation that is further complicated by the enormous risk of contamination from modern human DNA. Only a few labs around the world have built sterile “aDNA” labs to protect against this.

  Now, in addition to all the different ways of finding out about the past through the genomes of modern humans, we have begun to build a library of ancient genomes. We can compare the DNA of ancient people to modern humans and also compare the ancients to one another. Reich led a pioneering study that compared the mtDNA of 364 ancient individuals who lived in one of nine different European cultures between 1,550 and 5,500 years ago. (Because there are so many copies of mtDNA in any one cell, it is much easier to recover from ancient remains than nuclear DNA.) The team found that the way mtDNA transformed over time revealed a pattern of stasis interrupted by change. After farming was first introduced to central Europe, not much about the genetics changed for 2,500 years; after that the genetics associated with the farmers began to spread. Reich’s team found four significant incidents where a population either expanded or was replaced by another population which they lined up against significant cultural moments, such as the introduction of the horse and the beginning of metallurgy.

  A 2014 study used the DNA of ancient farmers and hunter-gatherers from Europe to explore an age-old conundrum: Did farming sweep across Europe and become adopted by the resident hunter-gatherers, or did farmers sweep across the continent and replace the hunter-gatherers? The study found a significant difference between the DNA of the two groups, suggesting that even though there may have been some flow of hunter-gatherer DNA into the farmers’ gene pool, for the most part the farmers replaced the hunter-gatherers.

  Now we have answers to the questions that couldn’t be addressed just two years ago. What exactly is Neanderthal DNA doing in the human genome? Is it merely the reminder of a long-ago encounter, a random series of segments that have drifted throughout the genome? Or were some segments of Neanderthal DNA retained because they shaped us in useful ways?

  Even though most non-African individuals have 1 percent to 3 percent Neanderthal DNA (I have 2.7 percent), it appears that over 60 percent of the Neanderthal genome is distributed in small pieces throughout the non-African human population. A number of teams have demonstrated that it may have helped the earliest African migrants adapt to a colder, darker climate. Some parts of the genome with a high frequency of Neanderthal variants shape hair and skin color and likely made the first Eurasians lighter-skinned than their African ancestors. Other regions that have been influenced by the Neanderthal genome are implicated in human diseases, such as lupus, Crohn’s disease, and type 2 diabetes, and even in behavior, such as addiction to cigarettes. Some Nean
derthal DNA appears to be more useful to one population than to another. Europeans, but not East Asians, have more Neanderthal DNA in regions of the genome responsible for lipid catabolism, the processing of cholesterol and fatty acids and related molecules.

  It may even be that some Neanderthal DNA was selected against. There are regions in the human genome where no Neanderthal DNA can be found at all, such as genes that are significantly expressed in human testes. Perhaps the individuals who first inherited those segments were not successful at passing them on.

  Not long after the Neanderthal genome was sequenced, Pääbo’s team discovered that some people carry DNA from an entirely different ancient species, now known as the Denisovans. Until 2010 we didn’t even know Denisovans existed, and although all we have of them today is a few tiny bones and a couple of teeth found in a cave in the Altai Mountains in Siberia, scientists were able to extract DNA from these remains and compare it to the genomes of modern people. The Denisovans may have spread as far as Southeast Asia. Indigenous Australians, Melanesians, and some groups in Asia have up to 5 percent Denisovan DNA, in addition to their Neanderthal DNA. It’s been suggested that an early group of humans may have left Africa, met with Denisovans in Asia, and then spread their genes out from there, bringing them into Australia more than fifty thousand years ago.

  The only group that doesn’t seem to have traces of either Neanderthal or Denisovan DNA—at least from this period of history—is sub-Saharan Africans. Yet researchers are examining the African genome for evidence of earlier mixing with archaic human beings. In 2011 it was announced that some Africans carry DNA from an entirely different, as yet unknown, species.

  The fact that we carry this ancient nonhuman DNA changes how we view not only humans and nonhumans but also the entire narrative arc of ancient history. We’ve always imagined the migrations of humans out of Africa as a hero’s journey, with a small band of gutsy wanderers setting off intrepidly into the unknown. But it seems that even then there was no terra nullius. The residents of planet Earth included not just Neanderthals and Denisovans but at least one more mysterious population: the hobbit, a tiny humanlike species who lived as recently as thirteen thousand years ago on an Indonesian island.

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  While the mixing of Neanderthals and humans was a special case of admixture because they were so distantly related, there have been many significant examples of populations merging in history. “The greatest changer of genetics in history—probably,” Marcus Feldman said, “has been colonialism, whether it’s the Mongolian invasion of all of central Asia, which left genes lying around all over the place, or the British colonization of Australia, which left a very large signature of British genes in the Aboriginal population, or the Hispanic colonization of the Americas.”

  As much as populations have split apart and bottlenecked, there have also been continuous waves of humanity, sweeping over one another and fusing, whether it’s a merging of two separate populations or the subsuming of one, where only a very small trace of either the invaders or the invaded remains in the genome.

  Genomics allows us to see effects of colonialism that took place thousands of years ago. Feldman and his group showed that beginning around five thousand years ago, the Bantu began spreading throughout Africa, and by three thousand years ago they had reached southern Africa, where they began to merge with many local groups. Because they were farmers, the Bantu pushed out many of the native populations, who were hunter-gatherers. Descendants of Pygmies who developed a working relationship with the Bantu now carry significant evidence of Bantu ancestry in their genomes. By contrast, said Feldman, Bushmen from Namibia, who haven’t been much in contact with either people of European ancestry or people of non-Bushman African ancestry, “don’t show much of any ancestry other than their own.”

  It’s possible to see how old the Bushman genome is by looking at how tightly Bushmen’s genes travel together when they are inherited. “Think about beads on a string,” Feldman explained, with each segment of DNA representing a bead. “Every time there is a generation, two beads next to each other have a chance of breaking and forming a new string. If that happens at a certain rate, then the likelihood that you’ll find your original two beads on the same string after a long time is pretty small.” This is linkage disequilibrium, and Feldman and his group have found that Bushmen have the lowest amount of linkage disequilibrium in the world, meaning their genomes have been cycling over and over for the longest amount of time.

  For most of the human genome’s history, before the age of mass transport, bottlenecks and admixtures have occurred at the speed of walking. But in more recent history the geographic trail has significantly decoupled from the genetic trail, as every mode of transport we have invented has hastened the splitting and mingling of the genome today. As Marcus Feldman pointed out, it became possible to carry out colonization on a massive scale in the era of the horse, as we see in Genghis Khan’s legacy.

  Still, it wasn’t until the development of big ships and the age of exploration, the slave trade, and large-scale immigration that huge genomic waves began to wash around the world. In 1511, when Portuguese apothecary Tomé Pires rode the trade winds to Malacca (a state in modern-day Malaysia), he discovered a multicultural port city where he counted over eighty tongues being spoken, including ones from Europe, Africa, Eurasia, China, and the islands of the South Pacific.

  By the time of Columbus’s voyage, slave trade among Europe, Asia, and the Middle East had been a key component of commerce for hundreds of years. Following the discovery and settlement of the Americas, including the Caribbean and Brazil, newly established sugar and cotton plantations required a massive influx of labor, which was supplied by slaves from West Africa. Today Brazil is second only to Nigeria in terms of population with ancestry dating back to the African population of the Middle Ages. Overall, 5.5 million Africans were shipped to Brazil between 1501 and 1866.

  Even before the potato famine of the mid-1800s, the Irish had begun leaving for the United States, Canada, and Australia. During and following the famine, emigration increased dramatically, and by 1890 40 percent of all Irish-born people were living outside of Ireland. Today, there are seventy million people worldwide who claim Irish heritage, of whom only five million live in Ireland. Before these modern emigrations, much of the Irish population had inhabited the island we call Ireland for thousands of years.

  The genome not only is a record of the fact of admixture but it can tell us something about how the mixing occurred. “The Y chromosomes of indigenous Americans is heavily biased towards European, whereas the mitochondria are not,” said Feldman, explaining that this reflects the fact that the colonists were all men. As they swept in, they killed much of the male population, effectively removing their Y chromosome, and bred with the indigenous women, whose offspring inherited the colonists’ Y. The children retained the mtDNA that was passed down by their mothers.

  This pattern is true for many populations, including the African American population. You can see in the modern genome that stories like that of Jefferson and Hemings were not an exception. Many African women bore the children of white men.

  According to Nick Patterson at the Broad Institute, when you have multiple waves of male invaders washing over a female group, it’s not just the Y that changes. While the mtDNA stays the same, the autosomal DNA may be replaced completely. You can also track more complicated patterns of history in the X chromosome because two thirds of the ancestry on the X chromosome is female (women have two X chromosomes and men have one). The signal of the X is more complicated than that of mtDNA, as it is a combination of male and female, but it’s weighted toward female history.

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  When I think about the forces that have changed our genome, I imagine massive apocalyptic clouds rolling across a dark sky, a world covered in ice, or a famine that leaves only the luckiest few standing. Or I just picture time, hundreds of deca
des rolling on, one after the other, crunching up and spitting out generations of people behind them, continually transforming the genome. But natural selection is not all cataclysm. Some events remolded half the species without any such thunder.

  Imagine a drink that, if consumed regularly, would completely shape the lives of the drinker’s descendants, generation upon generation, over many tens of thousands of years. It sounds like science fiction, but it’s ancient history. Before eight thousand years ago, humans could not easily digest milk after they had been weaned from their mothers. As people learned how to domesticate first goats, then sheep and cattle, they tried drinking the animals’ milk and then came to rely more and more on it for sustenance. In many parts of the world this became a crucial determinant of who was most likely to live and reproduce and who was not. Random mutation meant that some people could tolerate milk better than others, and these individuals passed on their tolerance to offspring who outsurvived the lactose intolerant. Milk drinking evolved several times over in different groups.

  The milk adaptation comes from the biology of culture, where ongoing changes in the human body resulted from choices people made as they created their environment. The way we normally think about natural selection (aka adaptation, aka survival of the fittest) is that a child is born with a genetic mutation that gives it an edge—whether stronger immunity or greater height—that enables it to be more successful in reproducing than its peers. Because the edgier offspring pass on their advantageous trait to more offspring, the new trait—and the DNA that underlies it—becomes more frequent in the population and possibly completely dominant. When natural selection shaped us in Africa we were a small enough group that it shaped the entire human genome. The gene for amylase is an example of the biology of culture via the ancient human kitchen. Amylase helps people process starch, and it was discovered in 2007 that the more starch a group of people eats, the more copies of the amylase gene they have. It’s not known if the starch-eaters have gained copies over time or if the non-starch eaters have lost them. It may be that one of the threads of the human journey is underscored by amylase—the better we could process starch, the more widely we were able to travel.