Outstanding questions in the study of archaic hominin admixture

Abstract

The complete sequencing of archaic and modern human genomes has revolutionized the study of human history and evolution. The application of paleogenomics has answered questions that were beyond the scope of archaeology alone-definitively proving admixture between archaic and modern humans. Despite the remarkable progress made in the study of archaic-modern human admixture, many outstanding questions remain. Here, we review some of these questions, which include how frequent archaic-modern human admixture was in history, to what degree drift and selection are responsible for the loss and retention of introgressed sequences in modern human genomes, and how surviving archaic sequences affect human phenotypes.

Fig 1. A simplified model of admixture history between archaic and anatomically modern human populations.

There is consensus that at least two independent gene-flow events occurred (solid arrows)—admixture from Neanderthals into an ancestral Eurasian population (solid blue) and from Denisovans into an ancestral Southeast Asia population (solid red). It is likely that additional instances of admixture occurred, explaining the variation in the percentage of archaic sequence across different global populations. These additional instances include a pulse of admixture from Neanderthals (dashed blue) and from Denisovans (dashed red) into an ancestral East Asian population. Alternatively, or in addition, global variation in archaic ancestry could be the result of admixture within human populations (dashed orange) diluting archaic sequence. Admixture from human populations may also have introduced sequence into archaic populations.

Fig 2. Patterns and characteristics of archaic sequence across the genome.

(A) A representation of individual genomes from archaic and modern human populations. The modern human genomes (orange) are ordered by increasing levels of Neanderthal (blue) admixture percentage (approximate). Only Asian populations carry Denisovan (red) sequence. Some introgressed archaic segments are shared across populations, and some large regions of the genome are deserted of introgressed archaic sequence in all populations examined. (B) Large deserts may be a product of selection against deleterious archaic variants (gold stars) at those loci. Whether selection acted against a few strongly deleterious variants (top) or many weakly deleterious variants (bottom) remains uncertain. (C) Many segments of introgressed archaic sequence are found to carry variants (stars) that affect gene regulation and expression. Altering gene expression may affect downstream protein levels (e.g., immunological proteins) and could have provided a mechanism of rapid adaptation for admixed modern humans. (D) Putatively adaptive introgressed segments can be identified by examining the frequency of introgressed segments (blue dots) within a population and filtering for those that exceed a percentile cutoff (dashed black line).