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As modern humans colonized the world, groups developed genetic differences that make it possible to distinguish Africans, Asians, and Europeans today—both visually and by using computer programs like structure. People, however, have continued to move within and among continents throughout history, blurring the genetic differences among populations. In some cases, the movements were extensive, as between Europe and Asia. In others, they were small but continuous, as between Asia and the Americas across the Bering Strait. Today, all human groups appear to be the product of complex mixings and movements of previous groups, not isolated populations that have remained separate and immobile for long periods.
Pritchard moved from Oxford to the University of Chicago in 2001, the same year the full sequence of the human genome was published. Completion of the Human Genome Project marked a milestone in the history of science, but it was just one genome and population geneticists wanted more. They wanted to know how DNA sequences differ from person to person, both to gauge the effects of those differences on health and to learn more about human history.
They did not have to wait long. In the 1990s, Cavalli-Sforza at Stanford had initiated an effort known as the Human Genome Diversity Project to gather hundreds of human DNA samples from around the world; the data Pritchard analyzed with structure were some of the first results from the project. In 2002, the National Institutes of Health launched a more intensive effort that identified millions of common DNA differences in several hundred people with African, European, and Asian ancestry.
As data on human genetic differences flooded into databases, population geneticists scoured the data for signs of selection. For example, a group led by Pardis Sabeti at Harvard University developed a mathematical technique to look for large sections of DNA that were unusually similar in many people. Nearly identical blocks of DNA suggested that the sections contained a genetic variant that had conferred an advantage on individuals with that variant, causing the representation of the variant to increase in the population. For example, Sabeti's research team found two genetic variants involved in resistance to malaria that appeared to have increased dramatically in frequency over the past few thousand years—about the same time frame when the development of agriculture caused populations of malaria-carrying mosquitoes to explode.
Soon other signs of selection popped up in DNA data. For example, the strongest signal of selection in the entire human genome emerged from the gene that encodes the enzyme lactase, which breaks down the sugar in milk, lactose, into more easily digested sugars. Most people in the world make lactase when they are children so they can digest their mother's milk, but the gene shuts off when they become adults. Many people with European, Middle Eastern, or African ancestry have a variant of the lactase gene that remains active in adulthood, so that they're able to digest milk their whole lives. These versions of the gene are most common in populations that domesticated animals for milk, which would have created a selective pressure for a lifelong ability to digest lactose. The genetic variants in these populations began to increase in frequency at about the same time that dairy animals were domesticated.
Another strong selective signal turned up in genes that affect skin color. As modern humans expanded out of Africa into more northern latitudes, their dark skin became a distinct disadvantage, probably because in high latitudes it blocks too much of the sunlight that humans need to synthesize vitamin D. Genetic variants that produced lighter skin therefore gained a significant advantage. In early Europeans, variants in several genes that lighten skin color began to increase in frequency. Meanwhile, the same process was occurring on the other side of Eurasia as dark-skinned people from southeastern Asia moved north, but there, different sets of variants became responsible for lighter skin.
Pritchard and other geneticists also began to find signs of selection in parts of the genome with unknown functions. In a 2006 paper, for example, he and a group of colleagues found selective signals scattered throughout the genome. Some signals were associated with genes of known function, but others appeared in genes of unknown function or even in areas that had no genes.