The Neanderthal population history and the introgression landscape inferred from the UK Biobank

Abstract

Neanderthal haplotypes in present-day Eurasians are unevenly distributed across the genome, forming introgression deserts and high-frequency segments consistent with adaptive introgression, with additional random variation affected by genetic drift. However, current estimates are limited by modest sample sizes and analyses restricted to subsets of the genome, given that any individual carries only 1-2% Neanderthal ancestry. Here we extract and analyse Neanderthal haplotypes from 45,000 imputed and phased genomes in the UK Biobank. Even at this scale, the number of sites overlapping Neanderthal haplotypes approaches--but does not reach--saturation, with rare haplotypes still being discovered. Using the derived allele frequency spectrum within the surviving Neanderthal segments, we infer a divergence time of 2,061 generations between the introgressed lineage and the Vindija Neanderthal, and estimate the effective population size of the introgressed lineage to Ne = 6,564. Individual-level resolution allows identification of 545 independent loci with excess Neanderthal homozygosity, consistent with ongoing selection. Despite the extensive dataset, a substantial portion of the genome remains a Neanderthal desert. Within these regions, we detect seven Human Accelerated Regions affected by recent human selective sweeps (TMRCA <650 kya), four located within introns of cerebellum-expressed genes, providing further support for their potential as modern human-specific adaptation.