Evolutionary dynamics of the human pseudoautosomal regions

Recombination between the X and Y human sex chromosomes is limited to the two pseudoautosomal regions (PARs) that present quite distinct evolutionary origins. Despite the crucial importance for male meiosis, genetic diversity patterns and evolutionary dynamics of these regions are poorly understood. In the present study, we analyzed and compared the genetic diversity of the PAR regions using publicly available genomic sequences encompassing both PAR1 and PAR2. Comparisons were performed through allele diversities, linkage disequilibrium status and recombination frequencies within and between X and Y chromosomes. In agreement with previous studies, we confirmed the role of PAR1 as a male-specific recombination hotspot, but also observed similar characteristic patterns of diversity in both regions although male recombination occurs at PAR2 to a much lower extent (at least one recombination event at PAR1 and in approximate to 1% in normal male meioses at PAR2). Furthermore, we demonstrate that both PARs harbor significantly different allele frequencies between X and Y chromosomes, which could support that recombination is not sufficient to homogenize the pseudoautosomal gene pool or is counterbalanced by other evolutionary forces. Nevertheless, the observed patterns of diversity are not entirely explainable by sexually antagonistic selection. A better understanding of such processes requires new data from intergenerational transmission studies of PARs, which would be decisive on the elucidation of PARs evolution and their role in male-driven heterosomal aneuploidies. Author summary The pseudoautosomal regions (PAR1 and PAR2) of the human sex chromosomes contain the unique blocks of homologous sequences between the X and Y chromosomes that allow pairing and recombination during male meiosis. Both PARs present a distinctive transmission behavior that includes the properties of either sex-linked or autosomal regions (hence the pseudoautosomal status). However, the type and extent of evolutionary forces acting on these regions are, so far, not totally clear. In this work, we aimed to study the genetic diversity patterns in the human PARs, taking advantage of the publicly available resource of human genetic variation provided by the 1000 Genomes Project. Our results showed a higher frequency of recombination in PAR1 when compared to PAR2, as well as, a fairly uneven distribution of recombination throughout both regions. Moreover, in both PARs, low recombination segments are consistently associated with increased linkage disequilibrium and significantly different allele frequencies between the X and Y chromosomes. Despite the discrepancy of male recombination rates (obligatory at PAR1 and in approximately equal to 1% of meiosis at PAR2), both regions harbor highly enriched stretches with regard to allele frequency differences among sexes, which are not counterbalanced by recombination, raising questions about underlying evolutionary forces (e.g., selection). Since our results do not fit the expectations of a sexually antagonistic model, new data based on fast evolving markers from intergenerational transmission studies of PARs are required for the elucidation of the evolutionary behavior and crucial role of these regions in male-driven sex-chromosome aneuploidies.