Integrating sex-bias into studies of archaic admixture on chromosome X

Evidence of interbreeding between archaic hominins and humans comes from methods that infer the locations of segments of archaic haplotypes, or ‘archaic coverage’ using the genomes of people living today. As more estimates of archaic coverage have emerged, it has become clear that most of this coverage is found on the autosomes— very little is retained on chromosome X. Here, we summarize published estimates of archaic coverage on autosomes and chromosome X from extant human samples. We find on average 7.9 times more archaic coverage on autosomes than chromosome X, and identify broad continental patterns in this ratio: greatest in American samples, and least in South Asian samples. We also perform extensive simulation studies to investigate how the amount of archaic coverage, lengths of coverage, and rates of purging of archaic coverage are affected by sex-bias caused by an unequal sex ratio within the archaic introgressors. Our results generally confirm that, with increasing male sex-bias, less archaic coverage is retained on chromosome X. Ours is the first study to explicitly model such sex-bias and its potential role in creating the dearth of archaic coverage on chromosome X. Author summary Tens of thousands of years ago, humans interbred with our close hominin relatives ( e . g . Neanderthals), which we know from finding segments of archaic hominin DNA in our genomes. Up to 4% of a human genome may be archaic DNA, but most of that archaic part is on the autosomes (the non-sex chromosomes). Chromosome X usually contains 3 to 10 times less archaic DNA than the autosomes. Also unlike the autosomes, it is always passed down by mothers, but only sometimes by fathers. There are several hypotheses for why chromosome X has less archaic DNA than the autosomes; one that has not been fully explored is whether the archaic hominins that interbred with our ancestors were mostly male or mostly female, known as ‘sex-bias’. In this paper, we use simulations to investigate whether sex-bias could produce less archaic DNA on chromosome X. Using simulation studies, we find that when the archaics are mostly male, modern humans end up with less archaic DNA on chromosome X than their autosomes, compared to when there is a female-bias or no sex-bias. Therefore, male sex-bias could be contributing to the difference in the amount of archaic DNA on chromosome X versus the autosomes. Of course, there are still plenty of other factors to be explored about how demography and selection have shaped our DNA. Studying patterns like this helps us learn more about early hominin natural history, and contextualizes archaic interbreeding events among other sex-biased events in human history. ### Competing Interest Statement The authors have declared no competing interest.