The nature of Neanderthal introgression — as revealed by 27,566 Icelandic genomes

These GEITP pages have often discussed publications about the Great Human Diaspora (migration of Homo sapiens, over the last 300,000 years, from eastern Africa to the rest of the world) and evolution in general — especially as it relates to environmental signals (diet and climate). Eurasian genomes are known to contain ~2% of their DNA from “archaic humans” related to Vindija Neanderthals (Vindija Cave is located in present-day northern Croatia, where Neanderthals resided ~40,000 years ago, ~8000 years before modern humans lived in that region; three Neanderthals from that cave are the primary source for the Neanderthal genome). In Europeans, “archaic ancestry” is consistent with contributions by a single population of Neanderthals through one or several pulses. Because many archaic fragments still segregate in contemporary populations, it seems reasonable that archaic genomes can be partially mined from whole-genome sequence data in Europeans. Once such archaic fragments are identified — it is possible to determine the effect that variants in these fragments have on phenotypic diversity (variability in traits) in modern humans.

Previous attempts to identify archaic fragments in contemporary humans have generally relied on existing archaic genomes, which partially represent the diversity of the archaic populations. Introgression is “movement of a gene or genes — from one species or subline into the gene pool of another — by the repeated backcrossing of a hybrid with one of its parent species or sublines.” The introgressing Neanderthals were probably from populations separated both in time and space from the three archaic individuals who have so far been sequenced to high coverage — hereafter referred to as DAV (Denisovan, Altai Neanderthal and Vindija Neanderthal). [Recall that Denisovans were first isolated from a cave in southern Russia; using the percent distance from human–chimpanzee as the last common ancestor, Denisovans/Neanderthals split from modern humans ~800,000 years ago, and from each ~640,000 years ago.] Some archaic fragments in contemporary humans will be missed by methods that depend on DAV genomes. Authors [see attached preprint] investigated the archaic diversity in contemporary Europeans and its relationship to the DAV genomes.

Interbreeding (admixure) of modern humans with Neanderthals was estimated to have taken place ~50,000-60,000 years ago. Authors examined the effect of “this event,” using 14.4 million putative archaic DNA fragments that had been detected in whole-genome sequences from 27,566 Icelanders (corresponding to a range of unique archaic fragments that cover 38.0% to 48.2% of the archaic genome). On the basis of similarity with known archaic genomes, authors assigned 84.5% of fragments to an Altai or Vindija Neanderthal origin and 3.3% to Denisovan origin; 12.2% of fragments are of “unknown origin” (suggesting one or more other archaic contributions might be “out there” somewhere). 😉

Authors found that Icelanders have more Denisovan-like fragments than expected; this is best explained by Denisovan gene flow, either into ancestors of the introgressing Neanderthals, or directly into modern humans. A within-individual, paired comparison, of archaic fragments — with syntenic (i.e. occuring on the same chromosome) non-archaic fragments — revealed that, although the overall rate of mutation is similar in humans and Neanderthals during the ~800,000 years their lineages have been separate, there are differences in the relative frequencies of mutation types (authors speculated that this is perhaps due to different generation intervals for males vs females). Lastly, authors assessed 271 traits (phenotypes), and identified five phenotype-genotype associations driven by variants in archaic fragments. Authors conclude that the majority of previously reported associations are better explained by DNA variants in the Homo sapiens genome, rather than by archaic variants.


Nature Apr 2020; 580:

This entry was posted in Center for Environmental Genetics. Bookmark the permalink.