Model-based detection and analysis of introgressed Neanderthal ancestry in modern humans

Abstract

Genetic evidence has revealed that the ancestors of modern human populations outside of Africa and their hominin sister groups, notably the Neanderthals, exchanged genetic material in the past. The distribution of these introgressed sequence-tracts along modern-day human genomes provides insight into the ancient structure and migration patterns of these archaic populations. Furthermore, it facilitates studying the selective processes that lead to the accumulation or depletion of introgressed genetic variation. Recent studies have developed methods to localize these introgressed regions, reporting long regions that are depleted of Neanderthal introgression and enriched in genes, suggesting negative selection against the Neanderthal variants. On the other hand, enriched Neanderthal ancestry in hair-and skin-related genes suggests that some introgressed variants facilitated adaptation to new environments. Here, we present a model-based method called diCal-admix and apply it to detect tracts of Neanderthal introgression in modern humans. We demonstrate its efficiency and accuracy through extensive simulations. We use our method to detect introgressed regions in modern human individuals from the 1000 Genomes Project, using a high coverage genome from a Neanderthal individual from the Altai mountains as reference. Our introgression detection results and findings concerning their functional implications are largely concordant with previous studies, and are consistent with weak selection against Neanderthal ancestry. We find some evidence that selection against Neanderthal ancestry was due to higher genetic load in Neanderthals, resulting from small effective population size, rather than Dobzhansky-Müller incompatibilities. Finally, we investigate the role of the X-chromosome in the divergence between Neanderthals and modern humans.

Recombination and selection against introgressed DNA

“…3.1 Initial purging of introgressed DNA Selection in the first generation after hybridization. Similar to previous work [e.g., Harris and Nielsen (2016); Juric et al (2016); Steinrücken et al (2018)], we assume that hybridization occurs as a pulse in a single generation (F0), such that a fraction x of F1 offspring are hybrids. Then, because all F1 hybrids carry exactly one-half introgressed DNA, E[P 1 ] = x/2 and Var(P 1 ) = x(1 − x)/4, so that, from Eq.…”

Introduction: Sex chromosomes and speciation

“…Steinrücken, Spence, Kamm, Wieczorek, and Song () revisit evidence for gene flow between Neanderthals and modern humans. Building on their earlier approach for reconstructing demographic history, Steinrücken et al.…”

“…Building on their earlier approach for reconstructing demographic history, Steinrücken et al. () present a new model‐based method for inferring admixed ancestry along chromosomes. Applying this demography‐informed strategy to population genomic data, the authors confirm that the human X harbours relatively less Neanderthal ancestry than autosomes.…”

“…After investigating genomic correlates of admixture, Steinrücken et al. () conclude that selection against gene flow stems from a higher load of deleterious mutations in Neanderthals and not hybrid incompatibilities.…”

Gene exchange between two divergent species of the fungal human pathogen,Coccidioides

“…However, given the high level of divergence, it is likely that at least some hybrid incompatibilities separate the two species of Coccidioides. This violates key assumptions required to use the distribution of introgressed haplotypes to infer the timing of admixture as hybrid incompatibilities are selected against making linked haplotypes shorter than expected under a neutral scenario (Racimo et al 2015;Juric et al 2016;Steinrücken et al 2018). Further studies are needed to determine how much divergence needs to accrue between fungal species to preclude the possibility of gene exchange.…”