Evolutionary Biology, Genetics
Harvard Medical School
Dr. Reich is also a senior associate member of the Broad Institute of Harvard and the Massachusetts Institute of Technology.
The Impact of Human Evolutionary History on Biology and Disease
Son of a novelist and a psychiatrist, David Reich says that he's always had "a deep interest in history and biology." He has combined those interests to make some surprising discoveries about human history, population movement, and evolution, including finding evidence that humans interbred with Neandertals between 35,000 and 85,000 years ago.
Despite his passion for biology and history, he majored in physics as an undergraduate. "I've always thought that the most important thing one could do was to study grand unified theory and figure out how the universe worked." He was unsure if he wanted to continue in physics after graduation, however, and he eventually decided to pursue a PhD degree in population genetics at Oxford University in the United Kingdom. A key lesson he absorbed during this period, he says, was "how to think critically about scientific research."
One idea he began to examine critically was the prevailing view of what happens when populations collide. "Throughout history, groups of humans have been on the move. Until recently, researchers did not have the ability to learn much about what happened when two populations met each other, and in particular whether they mixed or one replaced the other," Reich says. What really happens, he argues, is that populations mix, and that later people carry DNA from both ancestral groups.
Researchers can uncover DNA from the original populations through a technique called admixture mapping that Reich helped develop. "The idea is that populations of mixed ancestry are mosaics of chunks of DNA," he says. For example, he and his colleagues applied the technique to pinpoint a section of chromosome 8 in African Americans that was largely of African origin. The segment carries seven DNA variants that increase the likelihood of developing prostate cancer. The discovery explains why African Americans have a much higher risk of prostate cancer than do people of strictly European descent.
Reich and colleagues caused a sensation in 2010 when they turned their attention to DNA from ancient remains. He was one of the leaders of the team that first sequenced the genome of Neandertals, using DNA isolated from three limb bones. The researchers compared the Neandertal DNA to DNA of people from different continents and found that up to 4 percent of the DNA of today's non-Africans derives from Neandertals. In other words, humans and Neandertals had children together.
The predominant view in genetics at the time, Reich says, held that modern humans tramping into Eurasia from Africa had supplanted the Neandertals, not mated with them. The researchers didn't easily accept their evidence to the contrary. "We kept trying to make it go away, to find ways it was wrong," Reich says. But the finding held up. "It was a real eye-opener, and it contributed to the paradigm shift showing that population mixture is the rule, not the exception."
The evidence that many people today harbor Neandertal DNA was eye opening, but it wasn't off the wall—other researchers had raised the possibility of interbreeding. However, no one had suggested what Reich and colleagues discovered when they sequenced the genome of one of the Denisovan people, close kin of the Neandertals who lived in Siberia more than 30,000 years ago. The analysis revealed intermingling between modern humans and Denisovans. Their genetic traces show up in today's inhabitants of Australia, New Guinea, and the Philippines. "That's an amazing finding because even though the Denisova finger bone was found in Siberia, the Denisovans' genetic traces today are nearly absent in mainland Asia," Reich says. "The fact that their most important genetic contribution to people today is in island southeast Asia suggests that Denisovans were once spread over an enormous geographic range."
Reich's team has revealed more recent examples of mixing. His team found that most modern residents of India descend from two ancient populations that are genetically divergent, one from the northern part of the country and one from the south. The mixing mostly occurred from 2,000 to 4,000 years ago. Now Reich wants to look farther back in time. "Who was there before 4,000 years ago is a big mystery," he says.
What researchers learn about population mixing will influence other fields, such as history and anthropology, Reich says. "I predict it's going to have a big impact."