Skip to main content
Premium Trial:

Request an Annual Quote

Neanderthal DNA Not Continuously Removed From Modern Human Genomes Over Last 55K Years

NEW YORK (GenomeWeb) – There has been no long-term genome-wide removal of Neanderthal DNA from modern humans over the last 55,000 years, according to a paper published online today in the Proceedings of the National Academy of Sciences by Svante Pääbo and his colleagues at the Max Planck Institute for Evolutionary Anthropology in Germany.

These findings run contrary to recent studies that have claimed continuous selection against introgressed Neanderthal DNA, the researchers wrote, adding that these previous studies came to their conclusions thanks to "incorrect assumptions" about gene flow between African and non-African populations. And although they found that selection did occur after introgression, its effect was strongest in regulatory regions, suggesting that Neanderthals may have differed from humans more in their regulatory sequences than in their protein-coding sequences.

"Several studies have suggested that introgressed Neanderthal DNA was subjected to negative selection in modern humans. A striking observation in support of this is an apparent monotonic decline in Neanderthal ancestry observed in modern humans in Europe over the past 45,000 years," the authors wrote. "Here, we show that this decline is an artifact likely caused by gene flow between modern human populations, which is not taken into account by statistics previously used to estimate Neanderthal ancestry. When we apply a statistic that avoids assumptions about modern human demography by taking advantage of two high-coverage Neanderthal genomes, we find no evidence for a change in Neanderthal ancestry in Europe over the past 45,000 years."

The researchers used whole-genome simulations of selection and introgression to investigate a wide range of model parameters. They considered Neanderthal, West Eurasian, and African demographic histories, including simulations of introgression from Neanderthals into West Eurasians, and varying levels of migration between Africans and West Eurasians, and between African populations. They found that gene flow from West Eurasians into Africans lead to misestimates of Neanderthal ancestry and resulted in an incorrect inference of a continuous decline in Neanderthal ancestry.

The researchers used data from two Neanderthals — an individual from the Altai Mountains and one from the Vindija Cave in Croatia — to estimate Neanderthal ancestry. They were able to estimate the trajectory of Neanderthal ancestry in ancient and present-day Europeans and observed nearly constant levels of Neanderthal ancestry over time.

Previous studies have also seen the depletion of Neanderthal ancestry around functional genomic elements in modern human genomes as evidence for selection against Neanderthal introgressed DNA, the researchers explained. In order to examine this dynamic, they looked at the genomic distribution of Neanderthal markers at different time points in their simulations to determine whether their models could reproduce these signals. They found a strong negative correlation between the proportion of Neanderthal introgression surviving at a locus and distance to the nearest region under selection, similar to empirical results in modern humans.

The researchers also sought to determine whether particular functional classes of genomic sites were differently affected by Neanderthal introgression. They partitioned the human genome by functional annotation and by primate conserved regions. In seeming contrast with previous studies, they observed no significant depletion of Neanderthal ancestry in protein-coding sequences compared with intronic and intergenic regions. But they did identify a depletion of Neanderthal ancestry in both promoters and conserved regions, with both containing significantly less Neanderthal ancestry than gap regions.

"These results suggest that previously observed depletions in conserved and genic regions may not have been driven primarily by protein-coding differences between Neanderthals and modern humans, as was previously assumed, but rather by differences in promoters and other noncoding conserved sequence," the authors wrote. "This hypothesis is supported by several recent studies of the effects of introgressed Neanderthal sequences, including those with signatures of adaptive introgression, which found that surviving functional introgressed haplotypes have their major influence on gene expression regulation."

The researchers also concluded that these findings can be extrapolated to other cases where one species or population contributes a fraction of ancestry to another species or population, even in cases where the introgressing population carries a high burden of deleterious mutations. "Therefore, any long-term shifts in overall ancestry proportions over time are likely to be the result of forces other than negative selection, for example admixture with one or more other populations," they added.