Studies of ancient DNA are transforming our understanding of human evolutionary history and, in particular, how admixture (presence of DNA in an individual from a distantly-related population, as a result of interbreeding between populations who have been reproductively isolated and genetically differentiated) has shaped past and present patterns of human genomic variation. Of particular interest has been the discovery that admixture with archaic hominins has occurred multiple times throughout human history. In particular, ~2% of all non-African ancestry is derived from Neanderthals, with Oceanic populations having an additional 2%–4% of ancestry attributable to gene flow with Denisovans. This topic is relevant to these GEITP pages and gene-environment interactions, because such genetic variation among ethnic groups can result in different responses to drugs, environmental signals and chemicals, and even infectious agents.
The ability to identify introgressed hominin sequence [movement of a gene (gene flow) from one species — into the gene pool of another — by repeated backcrossing of an interspecific hybrid with one of its parent species] into the genomes of modern humans — enables us to infer ideas about the functional, evolutionary, and phenotypic significance of archaic admixture. For example, the genomic distribution of surviving Neanderthal and Denisovan lineages has been influenced by purifying selection [the selective removal of gene copies (alleles) that are deleterious], which has purged introgressed sequence that was deleterious in modern humans. Indeed, some exceptionally large regions depleted of archaic ancestry (also referred to as ‘archaic deserts’) have been identified and may be due to purifying selection. There is also strong evidence that some Neanderthal and Denisovan sequences were beneficial and therefore were rapidly retained at high frequency in modern human populations by a process known as adaptive introgression. In general, however, functional impacts of introgressed sequences, how they have been shaped by selection, and how they have influenced modern human health and disease — are only beginning to be explored.
Furthermore, a consistent observation in all studies of archaic hominin admixture is that East Asian populations have ~20% more Neanderthal ancestry compared to European populations. Numerous models have been invoked to explain this difference, including the interaction of demography (statistics e.g. births, deaths, income, or incidence of disease — which illustrate the changing structure of human populations) and selection, dilution by non-admixed populations, and/or additional population-specific admixture events.
Authors [see attached article & editorial] introduce a novel probabilistic method called IBDmix to identify introgressed hominin sequences, which, unlike existing approaches, does not use a modern reference population. Authors applied IBDmix to 2,504 individuals from geographically diverse populations to identify and analyze Neanderthal sequences segregating in modern humans; intriguingly, authors found that African individuals carry a stronger signal (i.e. longer stretches of Neanderthal DNA) of Neanderthal ancestry than previously thought. Authors show that this can be explained by genuine Neanderthal ancestry — due to migrations from Europe and Asia back to Africa, predominantly from ancestral Europeans, and by gene flow into Neanderthals from an early dispersing group of humans out of Africa. These findings refine our understanding of Neanderthal ancestry in African and non-African populations. These data also demonstrate that remnants of Neanderthal genomes survive in every modern human population studied to date.
Cell 20 Feb 2020; 180: 677-687 & editorial [Science 31 Jan 2020; 367: p 497