Signals interpreted as archaic introgression appear to be driven primarily by faster evolution in Africa

Abstract

Non-African humans appear to carry a few per cent archaic DNA due to ancient inter-breeding. This modest legacy and its likely recent timing imply that most introgressed fragments will be rare and hence will occur mainly in the heterozygous state. I tested this prediction by calculating D statistics, a measure of legacy size, for pairs of humans where one of the pair was conditioned always to be either homozygous or heterozygous. Using coalescent simulations, I confirmed that conditioning the non-African to be heterozygous increased D, while conditioning the non-African to be homozygous reduced D to zero. Repeating with real data reveals the exact opposite pattern. In African-non-African comparisons, D is near-zero if the African individual is held homozygous. Conditioning one of two Africans to be either homozygous or heterozygous invariably generates large values of D, even when both individuals are drawn from the same population. Invariably, the African with more heterozygous sites (conditioned heterozygous > unconditioned > conditioned homozygous) appears less related to the archaic. By contrast, the same analysis applied to pairs of non-Africans always yields near-zero D, showing that conditioning does not create large D without an underlying signal to expose. Large D values in humans are therefore driven almost entirely by heterozygous sites in Africans acting to increase divergence from related taxa such as Neanderthals. In comparison with heterozygous Africans, individuals that lack African heterozygous sites, whether non-African or conditioned homozygous African, always appear more similar to archaic outgroups, a signal previously interpreted as evidence for introgression. I hope these analyses will encourage others to consider increased divergence as well as increased similarity to archaics as mechanisms capable of driving asymmetrical base-sharing.

Keywords: D statistics; Neanderthal; heterozygosity; human; introgression; mutation rate.

Figure 1.

Variation in D between human populations and its dependence on whether sites are heterozygous or homozygous. All D values were calculated between pairs of individuals as D(P1,P2,N,C), where P1 and P2 are the two humans, arranged such that the population index (see Methods) of P1 is always less than or equal to the index of P2. The six panels represent different conditioning: thus, ANY, HOM indicates that only sites where P2 is homozygous are included, P1 being unconstrained. D values are averaged across all possible combinations within and between all populations / population combinations and colour coded by their mean value, varying from −0.1 (dark pink) through to 0.1 (dark blue). Actual values are tabulated in electronic supplementary material, table 1. The population/region of P1 is defined by the row and of P2 by the column. Thus, in the top left panel ‘ANY, HOM', the dark pink block indicates that D is large and negative whenever P1 is African and P2 (constrained to be homozygous) is either African or American, all other D values being close to zero.

Figure 2.

Conditioned D depends very little on individual identity. Within Africa, D always has large magnitude when one individual is conditioned. To confirm the implication that individual identity has minimal impact relative to the conditioning process, I considered all pairwise comparisons between individuals within one randomly selected African population, ESN, and for each comparison calculated D_ANY,HOM(African1,African2,N,C) and D_ANY,HOM(African2,African1,N,C), where N and C are the Neanderthal and chimpanzee, respectively. Note that all D-values are strongly negative even though a residual signal not due to conditioning is sufficient to drive a negative correlation, indicating that the conditioned homozygous individual is closer to the Neanderthal. In the axis legends, the conditioned homozygous individual is emphasized in red.