Using a novel method for detecting Neanderthal ancestry in modern humans, a team of U.S. researchers has demonstrated that remnants of Neanderthal genomes survive in every modern human population studied to date. They have found that modern African individuals have more Neanderthal DNA than previously thought; this can be explained by genuine Neanderthal ancestry due to migrations back to Africa, predominately from ancestral Europeans.
Detecting archaic introgression in modern humans without using an unadmixed reference panel reveals higher Neanderthal ancestry in African individuals than previously seen and suggests that back-to-Africa migrations contributed to this signal. Image credit: Neanderthal Museum.
“Our study is significant because it provides important new insights into human history and patterns of Neanderthal ancestry in globally diverse populations,” said senior author Dr. Joshua Akey, a scientist at Princeton University.
“Our results refine catalogs of genomic regions where Neanderthal sequence was deleterious and advantageous and demonstrate that remnants of Neanderthal genomes survive in every modern human population studied to date.”
Dr. Akey and his colleagues from Princeton University, the University of Washington, Seattle, and Microsoft developed a new computational method for detecting Neanderthal ancestry in the human genome.
Called IBDmix, their method enabled them for the first time to search for Neanderthal ancestry in African populations as well as non-African ones.
“This is the first time we can detect the actual signal of Neanderthal ancestry in Africans. And it surprisingly showed a higher level than we previously thought,” said co-author Dr. Lu Chen, a postdoctoral research associate in the Lewis-Sigler Institute for Integrative Genomics at Princeton University.
The IBDmix method draws its name from the genetic principle ‘identity by descent’ (IBD), in which a section of DNA in two individuals is identical because those individuals once shared a common ancestor.
The length of the IBD segment depends on how long ago those individuals shared a common ancestor.
For example, siblings share long IBD segments because their shared ancestor (a parent) is only one generation removed. Alternatively, fourth cousins share shorter IBD segments because their shared ancestor (a third-great grandparent) is several generations removed.
The researchers applied IBDmix to 2,504 modern individuals from the 1,000 Genomes Project, which represents geographically diverse populations, and used the Altai Neanderthal reference to identify Neanderthal sequence in these individuals.
They robustly identified regions of Neanderthal ancestry in Africans for the first time, identifying on average 17 megabases (Mb) of Neanderthal sequence per individual in the African samples analyzed (which corresponds to approximately 0.3% of the genome), compared with less than one megabase reported in previous studies.
More than 94% of the Neanderthal sequence identified in African samples was shared with non-Africans.
The scientists also observed levels of Neanderthal ancestry in Europeans (51 Mb/individual), East Asians (55 Mb/individual), and South Asians (55 Mb/individual) that were surprisingly similar to each other.
Strikingly, East Asians had only 8% more Neanderthal ancestry compared to Europeans, in contrast to previous reports of 20%.
“This suggests that most of the Neanderthal ancestry that individuals have today can be traced back to a common hybridization event involving the population ancestral to all non-Africans, occurring shortly after the Out-of-Africa dispersal,” Dr. Akeysaid.
To explore potential explanations for the unexpectedly high Neanderthal ancestry in Africans, the researchers then compared the actual data to simulated genotype data derived from different demographic models.
They found that Africans exclusively share 7.2% of Neanderthal sequence with Europeans, compared with only 2% with East Asians.
Simulations showed that low levels of back-migration persisting over the past 20,000 years can replicate features of the data and could therefore be a possible explanation for the observed levels of ancestry among different modern populations.
But gene flow went in both directions. The data also suggest that there was a dispersal of modern humans out of Africa approximately 200,000 years ago, and this group hybridized with Neanderthals, introducing modern human DNA into the genomes of Neanderthals.
“Both out-of-Africa and into-Africa dispersals must be accounted for when interpreting global patterns of genomic variation,” the study authors said.
A paper on the findings was published in the journal Cell.
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Lu Chen et al. Identifying and Interpreting Apparent Neanderthal Ancestry in African Individuals. Cell, published online January 30, 2020; doi: 10.1016/j.cell.2020.01.012
