No evidence for sex-differential transcriptomes driving genome-wide sex-differential natural selection

Sex differences in human transcriptomes have been argued to drive sex-differential selection (SDS). Here, we show that previous evidence supporting this hypothesis has been largely unfounded. We develop a method to test for a genome-wide relationship between sex differences in expression and selection on expression-influencing alleles (expression quantitative trait loci [eQTLs]). We apply it across 34 human tissues and find no evidence for a general relationship. We offer possible explanations for the lack of evidence, including that it is due in part to eQTL ascertainment bias toward sites under weak selection. We conclude that the drivers of ongoing SDS in humans remain to be identified.