Scientists Identify Neanderthal Genes in Modern Human DNA

Jan 30, 2014 by

In two new studies, genetic researchers have shown that about 20 percent of the Neanderthal genome survives in modern humans of non-African ancestry and identified exactly which areas of the human genome retain segments of Neanderthal DNA.

Neanderthal. Image credit: Trustees of the Natural History Museum, London.

Neanderthal. Image credit: Trustees of the Natural History Museum, London.

About 30,000 years ago, Homo sapiens migrating out of Africa began encountering Neanderthals, a lineage that had diverged from modern humans hundreds of thousands of years before. Despite their differences, Homo sapiens and Neanderthals mingled, and over time, produced children with genes from both lineages.

Today, the biological remnants of that collision between two distinct populations remain alive in the genomes of Europeans and East Asians.

The first study, reported in the journal Nature, examines how Neanderthals influence the genetic composition of modern humans.

Study’s senior author Dr David Reich of Harvard Medical School said: “the goal was to understand the biological impact of the gene flow between Neanderthals and modern humans.”

“We reasoned that when these two groups met and mixed, some new traits would have been selected for and remained in the human genome, while some incompatibilities would have been selected against and removed.”

“As methods to analyze ancient DNA continue to improve, we are able to get at answers to ever more fine-grained questions about our evolutionary history,” added Dr Elizabeth Tran of the National Science Foundation, who was not involved in the studies.

Dr Reich and his colleagues analyzed genetic variants in 846 people of non-African heritage, 176 people from sub-Saharan Africa, and a 50,000-year-old Neanderthal.

They showed that nine previously identified human genetic variants known to be associated with specific traits likely came from Neanderthals. These variants affect lupus, biliary cirrhosis, Crohn’s disease, optic-disk size and type 2 diabetes and also some behaviors, such as the ability to stop smoking. The team expects that more variants will be found to have Neanderthal origins.

The team also measured how Neanderthal DNA present in human genomes today affects keratin production and disease risk.

“Neanderthal ancestry is increased in genes affecting keratin filaments. This fibrous protein lends toughness to skin, hair and nails and can be beneficial in colder environments by providing thicker insulation. It’s tempting to think that Neanderthals were already adapted to the non-African environment and provided this genetic benefit to humans,” Dr Reich said.

The scientists also found that some areas of the modern non-African human genome were rich in Neanderthal DNA, which may have been helpful for human survival, while other areas were more like ‘deserts’ with far less Neanderthal ancestry than average.

“The barren areas were the most exciting finding. It suggests the introduction of some of these Neanderthal mutations was harmful to the ancestors of non-Africans and that these mutations were later removed by the action of natural selection,” said lead author Dr Sriram Sankararaman from the Harvard and MIT’s Broad Institute and Harvard Medical School.

The team showed that the areas with reduced Neanderthal ancestry tend to cluster in two parts of our genomes: genes that are most active in the male germline and genes on the X chromosome. This pattern has been linked in many animals to a phenomenon known as hybrid infertility, where the offspring of a male from one subspecies and a female from another have low or no fertility.

Dr Reich explained: “this suggests that when ancient humans met and mixed with Neanderthals, the two species were at the edge of biological incompatibility.”

“Present-day human populations, which can be separated from one another by as much as 100,000 years, are fully compatible with no evidence of increased male infertility. In contrast, ancient human and Neanderthal populations apparently faced interbreeding challenges after 500,000 years of evolutionary separation.”

The second study, published online in the journal Science, tests an innovative, fossil-free method for sequencing archaic DNA.

Co-authors Dr Benjamin Vernot and Dr Joshua Akey, both from the University of Washington, analyzed whole-genome sequencing data from 379 Europeans and 286 East Asians to identify Neanderthal lineages that persist in the modern DNA.

“We found evidence that Neanderthal skin genes made Europeans and East Asians more evolutionarily fit, and that other Neanderthal genes were apparently incompatible with the rest of the modern human genome, and thus did not survive to present day human populations,” Dr Vernot said.

The scientists observed that certain chromosomes arms in humans are tellingly devoid of Neanderthal DNA sequences, perhaps due to mismatches between the two species along certain portions of their genetic materials. For example, they noticed a strong depletion of Neanderthal DNA in a region of human genomes that contains a gene for a factor thought to play an important role in human speech and language.

The results suggest that significant amounts of population-level DNA sequences might be obtained from extinct groups even in the absence of fossilized remains, because these ancient sequences might have been inherited by other individuals from whom scientists can gather genomic data. Therein lies the potential to discover and characterize previously unknown archaic humans that bred with early humans.

“The fossil free method of sequencing archaic genomes not only holds promise in revealing aspects of the evolution of now-extinct archaic humans and their characteristic population genetics, it also might provide insights into how interbreeding influenced current patterns of human diversity,” Dr Vernot said.

“In the future, I think scientists will be able to identify DNA from other extinct hominin, just by analyzing modern human genomes.”

“From our end, this was an entirely computational project. I think it’s really interesting how careful application of the correct statistical and computational tools can uncover important aspects of health, biology and human history. Of course, you need good data, too.”


Sriram Sankararaman et al. The genomic landscape of Neanderthal ancestry in present-day humans. Nature, published online January 29, 2014; doi: 10.1038/nature12961

Benjamin Vernot and Joshua M. Akey. Resurrecting Surviving Neandertal Lineages from Modern Human Genomes. Science, published online January 29, 2014; doi: 10.1126/science.1245938