A selective difference between human Y-chromosomal DNA haplotypes

Abstract

DNA analysis is making a valuable contribution to the understanding of human evolution [1]. Much attention has focused on mitochondrial DNA (mtDNA) [2] and the Y chromosome [3] [4], both of which escape recombination and so provide information on maternal and paternal lineages, respectively. It is often assumed that the polymorphisms observed at loci on mtDNA and the Y chromosome are selectively neutral and, therefore, that existing patterns of molecular variation can be used to deduce the histories of populations in terms of drift, population movements, and cultural practices. The coalescence of the molecular phylogenies of mtDNA and the Y chromosome to recent common ancestors in Africa [5] [6], for example, has been taken to reflect a recent origin of modern human populations in Africa. An alternative explanation, though, could be the recent selective spread of mtDNA and Y chromosome haplotypes from Africa in a population with a more complex history [7]. It is therefore important to establish whether there are selective differences between classes (haplotypes) of mtDNA and Y chromosomes and, if so, whether these differences could have been sufficient to influence the distributions of haplotypes in existing populations. A precedent for this hypothesis has been established for mtDNA in that one mtDNA background increases susceptibility to Leber hereditary optic neuropathy [8]. Although studies of nucleotide diversity in global samples of Y chromosomes have suggested an absence of recent selective sweeps or bottlenecks [9], selection may, in principle, be very important for the Y chromosome because it carries several loci affecting male fertility [10] [11] and as many as 5% of males are infertile [11] [12]. Here, we show that one class of infertile males, PRKX/PRKY translocation XX males, arises predominantly on a particular Y haplotypic background. Selection is, therefore, acting on Y haplotype distributions in the population.

Testis development in the absence of SRY: chromosomal rearrangements at SOX9 and SOX3

“…1 In fact, in most XX males, SRY is transposed to the tip of Xp as a consequence of a recurrent Xp;Yp translocation, arising predominantly by nonallelic homologous recombination between PRKX and PRKY on a particular Y haplotypic background. 2,3 These males, usually with small testes, are essentially picked up among men with nonobstructive azoospermia.…”

Y chromosome haplogroups in autistic subjects

“…As a consequence, the frequency of this haplogroup would be higher in the autistic subjects compared to the control population. Indeed, several positive associations have already been reported between Y-chromosome haplogroups and various phenotypes including predisposition to XX male sex reversal, 23 infertility, 24 and alcoholism. 25 In this study, we searched for a specific Y chromosome effect in autistic subjects.…”

Critical role of Yp inversion in <i>PRKX/PRKY</i>-mediated Xp;Yp translocation in a patient with 45,X testicular disorder of sex development

“…Finally, direct sequencing was sequentially performed for the long PCR product, and the translocation fusion point inversion probably caused by a homologous recombination between ~300 kb long inverted repeats [7,8]. It has been suggested, therefore, that PRKX/PRKY-mediated translocations are prone to occur in Yp inversion positive males [7,9].…”

“…46,XX-TDSD (previously known as 46,XX maleness) and in those with SRY-negative 46,XY gonadal dysgenesis (previously known as 46,XY femaleness) have indicated the frequent occurrence of aberrant translocations between the homologous genes PRKX and PRKY [4][5][6][7]. In particular, most PRKX/PRKY-mediated translocations have taken place at two hot spots, i.e., the "hot spot A" at the 5' sequence that shares 97% sequence similarity over 1.7 kb and even 98.7% sequence similarity over 1.2 kb and the "hot spot B" around the C-terminal coding region that shares 90% sequence similarity over 2 kb and even 96% sequence similarity over 1 kb [5].…”