The Genome-wide Effects of Archaic Introgression from ‘Ghost’ Populations: A Case Study in Human Evolutionary History

The Effects of Gene Flow from Unsampled ‘Ghost’ Populations on the Estimation of Evolutionary History under the Isolation with Migration Model: Unsampled or extinct ‘ghost’ populations leave signatures on the genomes of individuals from extant, sampled populations, especially if they have exchanged genes with them over evolutionary time. This gene flow from ‘ghost’ populations can introduce biases when estimating evolutionary history from genomic data, often leading to data misinterpretation and ambiguous results. To assess the extent of this bias, we perform an extensive simulation study under varying degrees of gene flow to and from ‘ghost’ populations under the Isolation with Migration (IM) model. Estimates of popular summary statistics like Watterson’s θ, π, and FST , and evolutionary demographic history (estimated as effective population sizes, divergence times, and migration rates) using the IMa2p software clearly indicate that we a) under-estimate divergence times between sampled populations, (b) over-estimate effective population sizes of sampled populations, and (c) under-estimate migration rates between sampled populations, with increased gene flow from the unsampled ‘ghost’ population. Similarly, summary statistics like FST and π are also affected depending on the amount of gene flow from the unsampled ‘ghost’. The Genomic Landscape of Neanderthal Introgression in Modern European and East Asian Populations: Genomes of modern human populations outside of Africa share 1− 5% of identical by descent (IBD) haplotypes with Neanderthals, owing to multiple bouts of gene flow from this now extinct ‘ghost’ population. The recent availability of high quality archaic genomes has greatly improved our knowledge of the landscape of Neanderthal genomic variation in modern humans. However, our understanding of the evolutionary history of putatively introgressed Neanderthal genomic regions is still developing. Here we attempt to understand the combined effects of drift (i.e. population size) and linked natural selection across genomic regions of populations of Central European and Han Chinese ancestry that are introgressed from Neanderthals. We compile a composite genomic dataset from Altai Neanderthals, and unrelated Central Europeans from Utah (CEU), and Han Chinese (CHS/CHB) individuals from the 1000 Genomes Project, and estimate the evolutionary history across putatively introgressed regions. Our findings reveal (a) no significant (p > 0.05) differential introgression across all loci analyzed (i.e. no selection for or against introgression across all Neanderthal haplotypes), (b) no significant (p = 0.07) linked natural selection effects across all loci analyzed, but (c) greater support for some loci to have lower effective population sizes, and hence potentially under linked natural selection effects, including loci linked to the MAFK and GKAP1 genes, which are preferentially expressed in animal testes. Thus a larger, more encompassing study of genomic variation, supplemented with more complete Neanderthal (and other non-human hominid) genomes will help us delineate patterns of human evolutionary history