A central goal of human population genetics and paleoanthropology is to elucidate the relationships among ancient populations. Before the emergence of anatomically modern humans in the Middle Pleistocene ∼200 thousand years ago (kya), archaic humans lived across Africa, Europe, and Asia in highly differentiated populations. Modern human populations that expanded out of Africa in the Upper Pleistocene received a modest genetic contribution from at least two archaic hominin groups, the Neandertals and Denisovans., , , Especially in light of hypothesized genetic incompatibilities between Neandertals and modern humans, it is important to characterize differentiation between their ancestral populations and to investigate potential barriers to gene flow.
When populations diverge from one another, each retains a subset of the variation that existed in the ancestral population. Consequently, sequence divergence times usually exceed population divergence times, and this effect is more pronounced when the ancestral effective population size was large. In humans, a large fraction of genetic diversity is due to ancient polymorphisms that arose long before the emergence of anatomically modern traits. As a result, Neandertal and modern haplotypes are often no more diverged than modern human sequences are among themselves. This fact complicates the search for introgressed genomic segments, but two features facilitate their detection., First, due to low levels of polymorphism among Neandertals, introgressed sequences are often quite similar to those of the Neandertal reference. Second, these regions have elevated linkage disequilibrium due to the relatively recent date of admixture, ∼50 kya., , Although introgressed Neandertal sequences have been identified in modern human autosomes and X chromosomes, no mitochondrial genome (mtDNA) sequences of Neandertal origin have been reported in modern humans, and Neandertal Y-chromosome sequences have not yet been characterized.
Because uniparentally inherited loci have much smaller effective population sizes than autosomal or X-linked loci, the expected differences between sequence and population divergence times are smaller. Therefore, studying these loci can help to delineate an upper bound for the time at which populations last exchanged genetic material. To date, five Neandertal individuals have been whole-genome sequenced to 0.1× coverage or higher,, but all were female. Full mtDNA sequences are also available for eight individuals from Spain, Germany, Croatia, and Russia,, but the relationship between Neandertal and modern human Y chromosomes remains unknown.
In this work, we analyzed ∼120 kb of exome-captured Y-chromosome sequence from an ∼49,000-year-old (uncalibrated 14C) Neandertal male from El Sidrón, Spain. We compare it to the human and chimpanzee reference sequences and to the sequences of two Mbo individuals who carry the A00 haplogroup, the most deeply branching group known. We identify the relationship between the Neandertal and modern human Y chromosomes and estimate the time to their most recent common ancestor (TMRCA). We also examine coding differences and explore their potential significance for reproductive isolation.