X–Y Interactions Underlie Sperm Head Abnormality in Hybrid Male House Mice

Abstract

The genetic basis of hybrid male sterility in house mice is complex, highly polygenic, and strongly X linked. Previous work suggested that there might be interactions between the Mus musculus musculus X and the M. m. domesticus Y with a large negative effect on sperm head morphology in hybrid males with an F 1 autosomal background. To test this, we introgressed the M. m. domesticus Y onto a M. m. musculus background and measured the change in sperm morphology, testis weight, and sperm count across early backcross generations and in 11th generation backcross males in which the opportunity for X-autosome incompatibilities is effectively eliminated. We found that abnormality in sperm morphology persists in M. m. domesticus Y introgression males, and that this phenotype is rescued by M. m. domesticus introgressions on the X chromosome. In contrast, the severe reductions in testis weight and sperm count that characterize F 1 males were eliminated after one generation of backcrossing. These results indicate that X-Y incompatibilities contribute specifically to sperm morphology. In contrast, X-autosome incompatibilities contribute to low testis weight, low sperm count, and sperm morphology. Restoration of normal testis weight and sperm count in first generation backcross males suggests that a small number of complex incompatibilities between loci on the M. m. musculus X and the M. m. domesticus autosomes underlie F 1 male sterility. Together, these results provide insight into the genetic architecture of F 1 male sterility and help to explain genome-wide patterns of introgression across the house mouse hybrid zone.

Dobzhansky-Muller incompatibilities, dominance drive, and sex-chromosome introgression at secondary contact zones: A simulation study

“…; Janoušek et al. ; Campbell & Nachmann ). These clines are not always coincident, however, suggesting independent X‐A and Y‐A incompatibilities with different autosomal genes involved.…”

Sequence and structural diversity of mouse Y chromosomes

“…Rice (1984); Mueller et al (2013)), its functional portfolio is considerably more broad than that of the Y chromosome (Bellott et al 2014, 2017). The X chromosome also has a major role in hybrid sterility in mouse (Forejt and Iványi 1974; Forejt 1996; Storchová et al 2004; Payseur et al 2004; Teeter et al 2008; Good et al 2008; Campbell et al 2013; Turner et al 2014); the Y chromosome does not (Turner et al 2012; Campbell and Nachman 2014). We corroborate the “faster-X” effect on protein evolution that has been previously described by others (Kousathanas et al 2014; Larson et al 2016b) and show that it is strongest for genes expressed in the male germline (Figure 8), which are widely scattered across the X chromosome (Figure S2D).…”

Spermatogenesis and the Evolution of Mammalian Sex Chromosomes

“…However, it is still unclear how much of the observed sterility in Slx excess hybrids is due to downstream effects of disrupted MSCI in the same cross ( i.e. earlier disruption could have cascading effects on later cell stages), or other interactions between the X and Y chromosomes [99]. The phenotypic effects of Slx / Sly imbalance may also critically depend on interactions with other sex chromosome ampliconic regions and autosomal ampliconic gene regions that appear to be co-regulated with Sly [22,100,101].…”