How much Neanderthal DNA is in modern humans?

As Homo sapiens migrated out of Africa, tens of thousands of years ago, many members of the species interbred with Neanderthals and Denisovans along the way. But what sort of effect has this interbreeding had on the DNA of modern humans? Two different groups of US researchers decided to find out.

Studies have already shown that non-African individuals inherit about 2% of their genomes from Neanderthals, while people of Melanesian ancestry inherit another 2–4% of their genomes from Denisovan ancestors. But until now, it hasn’t been clear what influence those DNA sequences have had on our biology, traits and evolutionary history.

Scientists from the University of Washington (UW) conducted a study using genome-scale maps of Neanderthal and Denisovan sequences identified in more than 1500 geographically diverse people. While the vast majority of surviving Neanderthal and Denisovan sequences were found at relatively low frequencies (less than 5%), the analyses turned up 126 places in our genomes where these sequences exist at much higher frequencies, reaching up to about 65%.

The researchers’ study, published in the journal Current Biology, finds that the genes humans inherited from Neanderthals or Denisovans are important for our interactions with the environment. For example, Neanderthal and Denisovan sequences were found in seven parts of the genome known to play a role in the characteristics of our skin.

“The ability to increase to such high population frequencies was most likely facilitated because these sequences were advantageous,” said study co-author Joshua Akey. “In addition, many of the high-frequency sequences span genes involved in the immune system, which is a frequent target of adaptive evolution.

“Our work shows that hybridisation was not just some curious side note to human history, but had important consequences and contributed to our ancestors’ ability to adapt to different environments as they dispersed throughout the world,” Akey stated.

But while hybridisation apparently enabled humans to hold on to useful genetic material, geneticists from the University of California, Davis say the vast majority of this material was lost from the modern human population due to natural selection.

In an attempt to understand the causes of this loss, study leader Ivan Juric and his colleagues developed a method for estimating the average strength of natural selection against Neanderthal genetic material. The researchers found that natural selection removed many Neanderthal alleles from the genome that might have had mildly negative effects.

“Our results are compatible with a scenario where the Neanderthal genome accumulated many weakly deleterious variants, because selection was not effective in the small Neanderthal populations,” said Juric. “It is likely that these gene variations were able to persist in Neanderthals because Neanderthals had a much smaller population size than humans. Once transferred into the human genome, however, these alleles became subject to natural selection, which was more effective in the larger human populations and has removed these gene variants over time.

“Selection is more efficient at removing deleterious variants in large populations,” Juric elaborated. “Therefore, a weakly deleterious variant that could persist in Neanderthals could not persist in humans.”

Published in the journal PLOS Genetics, the study sheds new light on the role of population size on losing or maintaining Neanderthal ancestry in humans. It also confirms previous reports that East Asian people had somewhat higher initial levels of Neanderthal ancestry than Europeans. However, Juric admitted that the researchers “cannot conclude that differences in demography explain everything”.

“For instance, genes that were deleterious only in human–Neanderthal hybrids might have existed, and sexual selection or other forms of selection against hybrids could have been very important processes during human–Neanderthal hybridisation,” he said. “Still, I find it fascinating to think that if the Neanderthals had reached larger population sizes in Europe, or if modern human populations had grown slower, some of us today would probably carry a lot more Neanderthal ancestry in our genome.”

Image courtesy of Erich Ferdinand under CC BY 2.0