Beneficial liaisons

Modern populations acquired important immune system DNA from ancient, cross-species breeding

Sleeping around can expose you to diseases, but, at least in the course of human evolution, it may help you fight ’em. New research suggests that thousands of years ago humans acquired important immune system genes via liaisons with some of our extinct hominid cousins, the Neandertals and Denisovans. These dalliances may have allowed modern humans to persist in regions where unfamiliar pathogens may have otherwise killed them.

Many modern human populations appear to have the same versions of certain immune system genes found in those archaic relatives, a team of researchers reports online August 25 in Science. The Neandertal and Denisovan versions are most prevalent in modern populations in Europe and Asia. Because modern African populations harbor little to none of these archaic gene variants, the discovery suggests that humans acquired them after heading out of Africa and running into Neandertals and Denisovans in Europe and Asia.

“It’s amazing stuff,” says Daniel Geraghty, a specialist in genetics and immunology at the Fred Hutchinson Cancer Research Center in Seattle. “They have done a really great job of weaving together facts to come up with a very plausible and very powerful story of what might have happened to the human species as it expanded out of Africa.”

Previous research suggested that humans were interbreeding with both Neandertals and Denisovans, a closely related species known only from a fossil finger bone found in a Siberian cave. Modern Eurasian genomes contain up to 4 percent of Neandertal DNA, and the DNA of Melanesians of Papua New Guinea is 4 to 6 percent Denisovan (SN: 6/5/10, 1/15/11).

Laurent Abi-Rached of Stanford University School of Medicine in California
and colleagues decided to home in on three particular immune system genes called HLA genes, which help the body recognize foreign, potentially dangerous invaders. In fact, HLA matches in donors and recipients are crucial for transplants of organs and other tissues.

Using the genetic blueprints of three Neandertals, the one Denisovan, and present-day genetic information from bone marrow/stem cell donor registries, the researchers compared the frequencies of various versions of the HLA genes. Computer simulations were used to assess whether the observed frequencies were unusual.

The results indicate that humans were definitely producing offspring with Neandertals and Denisovans. In some instances those offspring acquired archaic versions of the genes that imparted such a benefit that they eventually became widespread. One Denisovan version of an HLA gene, for example, seems to be present in 50 to 60 percent of people in China and Papua New Guinea.  

Experts in evolution and genetics say the results are exciting but urge caution in interpreting the data. Because immune system genes would be subject to intense selection — having the wrong ones would be fatal — it isn’t clear exactly what factors shaped the present-day genetic patterns, says David Reich of Harvard Medical School and the Broad Institute in Cambridge, Mass. Reich was a lead researcher on the previous studies that unraveled the genomes of Neandertals and the Denisovan.

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