Complex history of admixture between modern humans and Neandertals

Abstract

Recent analyses have found that a substantial amount of the Neandertal genome persists in the genomes of contemporary non-African individuals. East Asians have, on average, higher levels of Neandertal ancestry than do Europeans, which might be due to differences in the efficiency of purifying selection, an additional pulse of introgression into East Asians, or other unexplored scenarios. To better define the scope of plausible models of archaic admixture between Neandertals and anatomically modern humans, we analyzed patterns of introgressed sequence in whole-genome data of 379 Europeans and 286 East Asians. We found that inferences of demographic history restricted to neutrally evolving genomic regions allowed a simple one-pulse model to be robustly rejected, suggesting that differences in selection cannot explain the differences in Neandertal ancestry. We show that two additional demographic models, involving either a second pulse of Neandertal gene flow into the ancestors of East Asians or a dilution of Neandertal lineages in Europeans by admixture with an unknown ancestral population, are consistent with the data. Thus, the history of admixture between modern humans and Neandertals is most likely more complex than previously thought.

Figure 1

Schematic Representation of R_ind and R_pop Two hypothetical populations, each with 20 sampled individuals, are shown. Each individual’s Neandertal ancestry is shown in blue (top), and the total amount of the Neandertal genome present in this region in each population is shown in dark gray (bottom). Estimates of summary statistics for these hypothetical regions are given (left). Note that the amount of Neandertal sequence per individual is quite different between populations—population 2 contains more Neandertal sequence per individual, as reflected by an R_ind value of ∼1.2. However, in each population the same amount of the Neandertal genome survives, as reflected by an R_pop value of ∼1.

Figure 2

Estimates of R_ind and R_pop as a Function of B-Value Cutoffs (A) Amount of the genome in each B-value category. Note that each category is a subset of the category to its left (i.e., the category B ≥ 0 contains the entire genome). (B and C) R_ind (B) and R_pop (C) calculated over genomic regions with progressively higher B-value thresholds (i.e., less functional constraint; see color bar). Violin plots show bootstrap resamples, and red dotted lines denote the 95% confidence intervals (CIs).

Figure 3

Inference of Admixture Models from Genomic Regions with Little or No Selective Constraint (A) Schematic illustration of the one- and two-pulse models of Neandertal introgression. The majority of introgression occurred in the common ancestor of all non-Africans (m₁), and a smaller additional amount of introgression occurred in East Asians (m₂). (B) Schematic illustration of the one-pulse and European-dilution models. All Neandertal introgression occurred in the common ancestor of Europeans and East Asians (m₁), and a substantial portion of modern-day European ancestry (A_X) derived from a second population (X) with no Neandertal ancestry. Below each demographic model are histograms of m₂/ m₁ (left; the proportion of additional introgression into East Asians) and A_X (right; the proportion of European ancestry derived from population X) as estimated by 30,000 simulations and ABC analysis (adjusted values of 1,500 accepted simulations are shown). Dashed lines demark 95% confidence intervals (CIs). Black arrows show the expected values of m₂/ m₁ (0) and A_X (0.023) under the one-pulse model.