Recombination Behaviour and Evolutionary History of the Extended Pseudoautosomal Region 1 (ePAR) on the Human Y chromosome

The human X and Y chromosomes are heterologous except at the tips of both arms - the pseudoautosomal regions (PARs). During male meiosis, crossover occurs only within these PARs, primarily in the Xp/Yp PAR1 which serves as an obligatory site of exchange. Although the boundary between PAR1 and the sex-specific region was thought to be conserved among primates, it has recently been found to differ among human males by a translocation of ~110 kb from the X to Y chromosome, generating an extended PAR1 (ePAR). This event occurred at least twice in human evolution. So far there has been limited indirect evidence to show that this extended homology domain actively supports recombination. This study asked if direct proof could be provided by investigating thousands of gametes from each of two ePAR-carrying men for two subregions, selected principally on published male X-chromosomal meiotic double-strand break (DSB) maps. Crossover behaviour between the X and the ePAR-borne segment on the Y is comparable to that of autosomal recombination hotspots for both the distal and proximal sites within the 110-kb extension. Other hallmarks of classical hotspots including evidence of transmission distortion and GC-biased gene conversion are also observed. This study also demonstrates correspondence between male DSB clusters and historical recombination activity in females within this region, as ascertained by linkage disequilibrium analysis. This suggests that this region is similarly primed for crossover in both males and females, although sex-specific differences may also exist. Additionally, extensive resequencing combined with the analysis of the Y phylogeny estimated a minimum crossover rate for ePAR that is at least six times higher than genome average. Finally, an examination of >200,000 Y chromosomes in UK Biobank revealed nine additional examples of ePAR, underlining the recurrent nature of the rearrangement, sponsored by non-allelic homologous recombination between specific dispersed repeats