Neanderthals gave us a selection of disease genes - [Journal article]

(BBC News, 30th January 2014) - Gene types that influence disease in people today were picked up through interbreeding with Neanderthals, a major study in Nature journal suggests.

Journal article: Resurrecting Surviving Neandertal Lineages from Modern Human Genomes

They passed on variants involved in type 2 diabetes, Crohn's disease and - curiously - smoking addiction.

Genome studies reveal that our species (Homo sapiens) mated with Neanderthals after leaving Africa.

But it was previously unclear what this Neanderthal DNA did and whether there were any implications for human health.

Between 2% and 4% of the genetic blueprint of present-day non-Africans came from Neanderthals.

By screening the genomes of 1,004 modern humans, Sriram Sankararaman and his colleagues identified regions bearing the Neanderthal versions of different genes.

That a gene variant associated with a difficulty in stopping smoking should be found to have a Neanderthal origin is a surprise.

It goes without saying that there is no suggestion our evolutionary cousins were puffing away in their caves.

Instead, the researchers argue, this mutation may have more than one function, so the modern effect of this marker on smoking behaviour may be one impact it has among several.

Researchers found that Neanderthal DNA is not distributed uniformly across the human genome, instead being commonly found in regions that affect skin and hair.

This suggests some gene variants provided a rapid way for modern humans to adapt to the new cooler environments they encountered as they moved into Eurasia. When the populations met, Neanderthals had already been adapting to these conditions for several hundred thousand years.

The stocky hunters once covered a range stretching from Britain to Siberia, but went extinct around 30,000 years ago as Homo sapiens was expanding from an African homeland.

Neanderthal ancestry was found in regions of the genome linked to the regulation of skin pigmentation.

"We found evidence that Neanderthal skin genes made Europeans and East Asians more evolutionarily fit," said Benjamin Vernot, from the University of Washington, co-author of a separate study in Science journal.

Genes for keratin filaments, a fibrous protein that lends toughness to skin, hair and nails, were also enriched with Neanderthal DNA. This may have helped provide the newcomers with thicker insulation against cold conditions, the scientists suggest.

"It's tempting to think that Neanderthals were already adapted to the non-African environment and provided this genetic benefit to (modern) humans," said Prof David Reich, from Harvard Medical School, co-author of the paper in Nature.

But other gene variants influenced human illnesses, such as type 2 diabetes, long-term depression, lupus, billiary cirrhosis - an autoimmune disease of the liver - and Crohn's disease. In the case of Crohn's, Neanderthals passed on different markers that increase and decrease the risk of disease.

Asked whether our ancient relatives actually suffered from these diseases too, or whether the mutations in question only affected the risk of illness when transplanted to a modern human genetic background, Mr Sankararaman said: "We don't have the fine knowledge of the genetics of Neanderthals to answer this," but added that further study of their genomes might shed light on this question.

Joshua Akey, from the University of Washington, an author of the Science publication, added: "Admixture happened relatively recently in evolutionary terms, so you wouldn't expect all the Neanderthal DNA to have been washed away by this point.

"I think what we're seeing to a large extent is the dying remains of this extinct genome as it is slowly purged from the human population."

However, some regions of our genomes were discovered to be devoid of Neanderthal DNA, suggesting that certain genes had such harmful effects in the offspring of modern human-Neanderthal pairings that they have indeed been flushed out actively and rapidly through natural selection.

"We find that there are large regions of the genome where most modern humans carry little or no Neanderthal ancestry," Mr Sankararaman told BBC News.

"This reduction in Neanderthal ancestry was probably due to selection against genes that were bad - deleterious - for us."

The Neanderthal-deficient regions encompass genes that are specifically expressed in the testes, and on the X (female sex) chromosome.

This suggests that some Neanderthal-modern human hybrids had reduced fertility and in some cases were sterile.

"It tells us that when Neanderthals and modern humans met and mixed, they were at the very edge of being biologically compatible," said Prof Reich.

Another genome region that lacked Neanderthal genes includes a gene called FOXP2, which is thought to play an important role in human speech.

Joshua Akey said his team's results were compatible with there having been multiple pulses of interbreeding between modern humans and Neanderthals.