Novel Y Chromosome Retrocopies in Canids Revealed through a Genome-Wide Association Study for Sex

Abstract

The lack of an annotated reference sequence for the canine Y chromosome has limited evolutionary studies, as well as our understanding of the role of Y-linked sequences in phenotypes with a sex bias. In genome-wide association studies (GWASs), we observed spurious associations with autosomal SNPs when sex was unbalanced in case-control cohorts and hypothesized that a subset of SNPs mapped to autosomes are in fact sex-linked. Using the Illumina 230K CanineHD array in a GWAS for sex, we identified SNPs that amplify in both sexes but possess significant allele frequency differences between males and females. We found 48 SNPs mapping to 14 regions of eight autosomes and the X chromosome that are Y-linked, appearing heterozygous in males and monomorphic in females. Within these 14 regions are eight genes: three autosomal and five X-linked. We investigated the autosomal genes (MITF, PPP2CB, and WNK1) and determined that the SNPs are diverged nucleotides in retrocopies that have transposed to the Y chromosome. MITFY and WNK1Y are expressed and appeared recently in the Canidae lineage, whereas PPP2CBY represents a much older insertion with no evidence of expression in the dog. This work reveals novel canid Y chromosome sequences and provides evidence for gene transposition to the Y from autosomes and the X.

Widespread intersex differentiation across the stickleback genome – The signature of sexually antagonistic selection?

“…The availability of a complete genome assembly including both sex chromosomes, and the rigorous elimination of sequences aligning to any of them, may potentially allow detecting genome-wide signatures of SAS based on intersex differentiation data alone (Lucotte et al, 2016), although the reliability of such approaches awaits validation. We also note that if the transfer of autosomal sequences to the Y chromosome includes genes that retain expression in the new location (Mahajan & Bachtrog, 2017;Tsai et al, 2019), autosomal genes may appear to show concurrent intersex differences in both allele frequency and gene expression levels when ignoring copies on a missing sex chromosome.…”

“…DNA segments closely related between autosomes and the Y chromosome may thus cause the alignment of Y-specific alleles to autosomes, thus potentially producing SNPs showing high intersex differentiation. This scenario leads to two testable predictions (see also Dou et al, 2012;McKinney, Waples, Seeb, & Seeb, 2017;Tsai, Evans, Noorai, Starr-Moss, & Clark, 2019).…”

“…This scenario leads to two testable predictions (see also Dou et al, 2012;McKinney, Waples, Seeb, & Seeb, 2017;Tsai, Evans, Noorai, Starr-Moss, & Clark, 2019). We here considered that both the reference genome and the new de novo genome are derived from a female (XX) individual.…”

“…Having ruled out reference genome misassembly as an explanation for strong autosomal differentiation between the sexes, we addressed a second hypothesis focused on reference genome incompleteness: that DNA segments similar to autosomal chromosome regions occur on the Y chromosome that is not part of any current genome assembly, and that these segments harbour private genetic variants that cause intersex differentiation when aligning to their autosomal counterparts (see also Tsai et al, 2019). Consistent with this idea, we observed that SNPs located within HIDRs showed a systematically reduced MAF in the female relative to the male pool ( Figure 2b).…”

“…This leads us to propose a model in which an autosomal DNA segment is first copied to the Y chromosome (see also Koerich, Wang, Clark, & Carvalho, 2008;Tsai et al, 2019), experiences mutation at the new location, and then, to variable extent, experiences further copy number expansion on the Y chromosome ( Figure 5). Consistent with this model, the male-female read depth ratios of the HIDR SNPs tended to form distinct clusters overlapping with 1.5, 2, and 2.5 (Figure 4) …”