Despite the challenge, Reich thought that detecting interbreeding could be important. It could expose some of humanity’s hidden history, or even shed light on why people are susceptible to certain diseases. When Reich arrived at Harvard Medical School, he began a study on prostate cancer that proved the value of this type of analysis by revealing the genes that make certain men more likely to develop such cancers. “Prostate cancer occurs 1.5 to 2 times more often in African American men than in European men,” Reich says. “We were able to find the reason why.”
To do so, Reich had to reconstruct the genetic history of African Americans, who came to the United States as slaves beginning in the 17th century. White owners sometimes had sex with their slaves and fathered children, thereby introducing European genes into the African American population. Freed slaves also had children with Native Americans and Latinos. As a result, African Americans today may have up to 80 percent European DNA.
Was it possible that Europeans and Asians had a little Neanderthal DNA after all?
Reich and his colleagues inspected the DNA of 1,597 African American men with prostate cancer. They surveyed around 1,300 short segments scattered through the men’s genomes and compared them with the same locations in the genomes of men from Europe, Asia, and Africa. They were able to determine which continent each segment in each African American man’s genome had come from.
Reich and his colleagues found seven genetic risk factors, which together constituted a hot spot of cancer risk. African American men who had the European version of all seven of the markers were no more likely to get prostate cancer than Europeans were; the African versions, though, were associated with elevated risk. The seven sites appear to control a gene involved in cell division. Mutations to those sites lead to cells’ multiplying too quickly.
Interbreeding in the United States took place over just the past few centuries. For his next project, Reich took on a much bigger challenge: the entire ethnic history of India. Today 1.21 billion people live in India. Their cultural variety is staggering: The country is home to 2,000 ethnic groups, and every Indian banknote has to have its value printed in 15 languages.
Reich wanted to see if the DNA of Indians contained clues about their origins as a people. Did they all descend from the same founding population, or could he tease apart DNA passed down from different ancestral groups?
He collaborated with scientists from the Centre for Cellular and Molecular Biology in Hyderabad to analyze the DNA of 132 Indians. Their subjects represented 25 ethnic groups, ranging from the Kashmiri Pandit, who live near the base of the Himalayas, to the Kurumba, who inhabit the southern tip of India.
In each person’s DNA, the scientists surveyed 560,000 sites, comparing each site in each Indian. The researchers also compared the data with that of groups of people outside India, including Europeans and Africans.
Reich and his colleagues programmed a computer to carry out a thorough analysis of these tens of millions of data points. The computer then created a range of possible genealogical trees and measured how well each tree could explain the genetic variations found across India. In 2009 the scientists reported that Indians can trace much of their DNA to just two ancestral populations.
“It’s a mixture between populations that are as different from each other as East Asians are from Europeans,” Reich says.
One population came from the same stock as the people of the Andaman Islands in the Indian Ocean. They arrived on the Indian subcontinent perhaps 40,000 years ago, and their descendants made up most of the population of India until maybe a few thousand years ago.
Then a second group, closely related to the ancestors of Europeans, appeared on the subcontinent. When the two groups made contact, they began to intermarry, mixing their genes together. In some ethnic groups, their DNA is now almost entirely blended. But in the far north and south of the subcontinent, the genes have mixed far less.
This discovery impressed Reich with the importance of interbreeding in human history. “You might think we’re living in special times now,” he says. “But we’ve been mixing quite often with distant relatives in our history.” And the statistical methods that Reich and his colleagues designed to probe the history of India proved crucial for his project deciphering the far earlier relationship of humans and Neanderthals.
Ever since Reich wrote his article about Neanderthal DNA back in 1997, Pääbo had been pushing to get more of their genes. By 2010 he and his colleagues had created a rough draft of the entire Neanderthal genome, comprising over 60 percent of its more than 3 billion base pairs.
Pääbo could now return to the question of how Neanderthals and humans were related, with thousands of times more data. But in order to make sense of the huge amount of DNA he had, he needed to work with people who were experts on how the relationships between populations can be gleaned from DNA—people like Reich.
“For our community it was always the great question, what the history of Neanderthal and modern human interactions was,” Reich says. “And the data Pääbo was gathering was a great way to get into it.”
The Neaderthal Within Us
Reich and his colleagues began analyzing Pääbo’s Neanderthal genome in 2007. They worked their way through the DNA in much the same way they had looked at the genes of Indians. They compared each site in the Neanderthal genome to the corresponding site in the genomes of humans, as well as the genome of a chimpanzee. Once more, they tried to work out the most likely evolutionary history that would explain the evidence.
“We were assuming Neanderthals and humans had not mixed,” Reich says. After all, that’s what Pääbo had initially found in 1997, looking at a tiny snip of mitochondrial DNA. And when he was able to look at larger pieces of mitochondrial DNA, he got the same result.
Most of the Neanderthal genes Reich and his colleagues looked at again supported Pääbo’s earlier research. In other words, all the human versions resembled each other more than any of them resembled the Neanderthal version. But then their computers began to spit out some strange results.
Chunks of Neanderthal DNA turned out to be more similar to the corresponding chunks of Europeans and Asians than they were to African DNA. On the other hand, in no case did Africans and Neanderthals share similar versions of a gene, to the exclusion of other humans. Was it possible that Europeans and Asians had a little Neanderthal DNA after all?