Genetic Diversity on the Human X Chromosome Does Not Support a Strict Pseudoautosomal Boundary

Abstract

Unlike the autosomes, recombination between the X chromosome and the Y chromosome is often thought to be constrained to two small pseudoautosomal regions (PARs) at the tips of each sex chromosome. PAR1 spans the first 2.7 Mb of the proximal arm of the human sex chromosomes, whereas the much smaller PAR2 encompasses the distal 320 kb of the long arm of each sex chromosome. In addition to PAR1 and PAR2, there is a human-specific X-transposed region that was duplicated from the X to the Y chromosome. The X-transposed region is often not excluded from X-specific analyses, unlike the PARs, because it is not thought to routinely recombine. Genetic diversity is expected to be higher in recombining regions than in nonrecombining regions because recombination reduces the effect of linked selection. In this study, we investigated patterns of genetic diversity in noncoding regions across the entire X chromosome of a global sample of 26 unrelated genetic females. We found that genetic diversity in PAR1 is significantly greater than in the nonrecombining regions (nonPARs). However, rather than an abrupt drop in diversity at the pseudoautosomal boundary, there is a gradual reduction in diversity from the recombining through the nonrecombining regions, suggesting that recombination between the human sex chromosomes spans across the currently defined pseudoautosomal boundary. A consequence of recombination spanning this boundary potentially includes increasing the rate of sex-linked disorders (e.g., de la Chapelle) and sex chromosome aneuploidies. In contrast, diversity in PAR2 is not significantly elevated compared to the nonPARs, suggesting that recombination is not obligatory in PAR2. Finally, diversity in the X-transposed region is higher than in the surrounding nonPARs, providing evidence that recombination may occur with some frequency between the X and Y chromosomes in the X-transposed region.

Sex-linked markers in the North American green frog (Rana clamitans) developed using DArTseq provide early insight into sex chromosome evolution

“…One explanation is that these loci are linked and lie on region of the Y-chromosome experiencing recombination with the X-chromosome, which can even frequently occur in species like humans [48]. While these loci typically diagnose sex accurately in the rest of our samples, it is important to note possible linkage might produce ambiguous genetic sexes for certain individuals.…”

Genetic Diversity on the Sex Chromosomes

“…But, pseudoautosomal regions are not static, sometimes changing in length dramatically across species (Raudsepp et al. 2012), and genetic diversity may not support a strict pseudoautosomal boundary (Cotter et al. 2016).…”

Recombination changes at the boundaries of fully and partially sex-linked regions between closely related Silene species pairs

“…The reasons for the repeated formation of new evolutionary strata, or for the possible gradual extension of sex chromosomes' nonrecombining regions, are not yet fully understood, and the mechanisms involved are not completely known in most species, with new mysteries emerging about the PAR boundary even in well-studied species such as humans (Cotter et al, 2016). One plausible reason/ cause for the situation driving changes in the PAR boundary (and creation of new strata) involves sexually antagonistic mutations (advantageous in one sex but disadvantageous in the other, often abbreviated to SA).…”