Neanderthals died out a long time ago, but their genes may make us more susceptible to certain diseases.
DNA inherited from Neanderthals affects which of our genes are turned on or off, according to a study published today in Cell. This phenomenon, called regulation of gene expression, means that traits such as height and susceptibility to diseases like schizophrenia or lupus may be affected in people with Neanderthal ancestry, say scientists from the University of Washington in Seattle.
This isn’t the first study to show that Neanderthal genes may affect modern humans: last year, a study previously published in Science found a small but measurable tie between Neanderthal genes and certain skin and blood conditions. It also suggested that certain conditions and susceptibilities inherited from Neanderthals may have served a useful purpose at one point. People who aren’t of African descent can thank Neanderthals for 1 to 4 percent of their genes.
This new study uses genetic data from tissues instead of medical records, and looks specifically at how the Neanderthal sequences affect which genes are turned on or off in modern humans, says Joshua Akey, co-author of the study and geneticist at the University of Washington. The researchers found that the effects of Neanderthal genes were “pervasive.”
“We carry a lot of the Neanderthal genome in scattered bits and pieces among individuals today, and if we understand the Neanderthal genome and its function better, then we’ll understand the human genome and its function better,” says Akey.
The researchers sampled 52 tissues in the body. All of them showed no preference for the human-pattern or Neanderthal-pattern gene expression — except two, the brains and the testes. In the brains and testes, the Neanderthal versions of genes were rarely active. That suggests that gene regulation between modern humans and Neanderthals differed the most in those tissues, Akey says.
“I think it’s a really exciting study,” says Sriram Sankararaman, a computer scientist and geneticist at UCLA, who wasn’t involved in the study. “It’s answering a really important question in human evolution.”
The influence of Neanderthal genes on traits also reveals that we have changed as a species as a result of ancient interbreeding. “I think that’s very exciting to see,” says Rasmus Nielsen, an evolutionary biologist at the University of California, Berkeley, who did not work on the study. “It changes our view of how we understand ourselves as a species and how we understand human evolution.”
The researchers used a massive public dataset to study 52 different tissues across 214 individuals. Called the Genotype-Tissue Expression (GTEx) Project, the dataset catalogues RNA levels in 53 tissues across multiple individuals. It was so complex that the researches developed their own statistical method in order to take full advantage of its features.
“This is a clever use of a large publicly available dataset to investigate an important evolutionary question about the effects of interbreeding with Neanderthals on modern humans,” John Capra, principle investigator at Vanderbilt University’s Capra Lab who did not work on the study, said in an email to The Verge.
Sankararaman says that the study’s design also shows a possible way forward in researching Neanderthal DNA. While the researchers used a dataset to analyze multiple tissues in individuals, looking elsewhere might lead to new discoveries. “One big direction is, what happens when you look at additional tissues that have not been sampled so far and look at what genes are turned on and off and how Neanderthal genes affect the regulation,” says Sankararaman.
The next project the group plans to tackle is gene expression in people of Melanesian ancestry, who carry sequences inherited from the Denisovan people. Akey also says that he’s interested in analyzing geographically diverse populations, and believes that studying worldwide populations may lead to the discovery of previously unknown groups of archaic humans.
The new study might also help researchers better understand the functional aspects of genetics and our shared evolutionary history, says Nielsen. Even though the last time that modern humans and Neanderthals interbred was tens of thousands of years ago, the consequences remain measurable. For Akey, that’s “fascinating.”