Sunday, October 17th, 2021

The Neanderthal DNA you carry may have surprisingly little impact on your looks, moods

Icelanders didn’t get their freckles and occasional red hair from Neanderthal ancestors.

PhotoAlto / Alamy Stock Photo

If you think you got your freckles, red hair, or even narcolepsy from a Neanderthal in your family tree, think again. People around the world do carry traces of Neanderthals in their genomes. But a study of tens of thousands of Icelanders finds their Neanderthal legacy had little or no impact on most of their physical traits or disease risk.

Paleogeneticists realized about 10 years ago that most Europeans and Asians inherited 1% to 2% of their genomes from Neanderthals. And Melanesians and Australian Aboriginals get another 3% to 6% of their DNA from Denisovans, Neanderthal cousins who ranged across Asia 50,000 to 200,000 years ago or so.

A steady stream of studies suggested gene variants from these archaic peoples might raise the risk of depression, blood clotting, diabetes, and other disorders in living people. The archaic DNA may also be altering the shape of our skulls; boosting our immune systems; and influencing our eye color, hair color, and sensitivity to the Sun, according to scans of genomic and health data in biobanks and medical databases.

But the new study, which looked for archaic DNA in living Icelanders, challenges many of those claims. Researchers from Aarhus University in Denmark scanned the full genomes of 27,566 Icelanders in a database at deCODE Genetics in Iceland, seeking unusual archaic gene variants. The researchers ended up with a large catalog of 56,000 to 112,000 potentially archaic variants—and a few surprises.

They found, for example, that Icelanders had inherited 3.3% of their archaic DNA from Denisovans and 12.2% from unknown sources. (84.5% came from close relatives of the reference Neanderthals.)

Next, the researchers calculated the association of the Neanderthal and Denisovan DNA with 271 traits. Unlike most previous studies, the team examined whole genomes, which allowed them to evaluate whether modern human genes were also influencing traits. They found that most traits were better explained by association with modern gene variants. Only five traits were notably influenced by archaic DNA, the researchers report today in Nature. Men with one archaic variant had a slightly reduced chance of prostate cancer, and both men and women carrying two other variants may have reduced height and accelerated blood clotting, says bioinformatician Laurits Skov, a postdoc at the Max Planck Institute for Evolutionary Anthropology, who led the research while at Aarhus and deCODE. 

Contrary to previous studies, the researchers found no statistically significant association between archaic DNA and freckles, hair color, eye color, or autoimmune diseases like Crohn disease and lupus. They conclude that Neanderthal DNA only has small effects on complex traits such as height or depression, in which many genes interact. (The team did not examine immune function or cranial shape, for which there is strong evidence of Neanderthal influence.)

Population geneticist Joshua Akey of Princeton University says the discovery of Denisovan DNA in Icelanders is “fascinating.” He notes that it likely didn’t come from a Denisovan who paddled to Iceland, but from a Neanderthal or modern human who mixed it up with a Denisovan long before present-day Icelanders reached the island.

But he adds that the relatively small impact of Neanderthal DNA on most traits is not surprising given that our genomes are mostly modern DNA. Max Planck computational biologist Janet Kelso agrees, but says archaic DNA may have different effects in Icelanders than in other populations.

For now, says geneticist Kári Stefánsson, CEO of deCODE and lead author of the study, “We [just] have to swallow the fact” that Neanderthal DNA doesn’t make as much of a difference as previous studies claimed. But his team has further work planned to clinch the case: They will study how Neanderthal and Denisovan genes are expressed by studying levels of more than 5000 proteins in Icelanders in the deCODE data base.

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