Mild reproductive impact of a Y chromosome deletion on a C57BL/6J substrain

Abstract

A recently reported deletion of about 40 Mb in length between 6.12/6.57 and 46.73/47.31 Mb on the Y chromosome long arm of the C57BL/6JBomTac inbred strain made us closely examine the strain’s breeding history and reproductive characteristics. We verified that the two copies of Rbm31y that are present inside the putative deletion were indeed deleted. This inbred strain presents an expected litter size for a C57BL/6 substrain. In vitro fertilization (IVF) efficiency and breeding efficiencies are comparable to those of the C57BL/6NTac substrain; however, the male/female sex ratio in the C57BL/6JBomTac is mildly skewed towards females. There is an increase in the percentage of sperm shape abnormalities found in C57BL/6JBomTac (35%) versus C57BL/6NTac (11%). The most frequent type of sperm abnormality observed is bent heads (19%). Additionally, there is deregulation of several transcripts expressed in the testes. We determined that this mutation arose in the C57BL/6JBomTac Foundation Colony in 2008, and it was completely fixed in the colony by 2009.Electronic supplementary materialThe online version of this article (doi:10.1007/s00335-017-9680-0) contains supplementary material, which is available to authorized users.

Sequence and structural diversity of mouse Y chromosomes

“…Larson et al (2016a) have shown that, in spermatids from reciprocal F 1 hybrids between domesticus and musculus that are “mismatched” for Slx/Slxl1 and Sly , global X-chromosome expression is indeed perturbed in the direction predicted by the copy number and actions of SLX/SLX1 and SLY. Second, several independent deletions of Yq in laboratory stocks converge on a similar phenotype, namely low fertility, abnormal sperm morphology due to problems with chromatin compaction, and sex-ratio distortion in favor of females (Styrna et al 1991; Conway et al 1994; Touré et al 2004; Fischer et al 2016; MacBride et al 2017). Third, Y chromosomes from musculus — the subspecies with highest Sly copy number — are more successful at introgressing across domesticus-musculus hybrid zone in Europe, and in localities where they do, the census sex ratio is shifted towards males (Macholán et al 2008).…”

Differential sperm motility mediates the sex ratio drive shaping mouse sex chromosome evolution

“…This is ascribed to a rampant and ongoing genomic conflict between the X and Y chromosomes over the control of offspring sex ratio. Partial deletions of the long arm of the Y chromosome (Yq) lead to sperm head malformation, sperm DNA damage, overexpression of sex-linked genes in spermatids and either a distorted offspring sex ratio in favour of females (for smaller deletions) or sterility (for larger deletions) [3][4][5][6][7].…”

“…Competition between Slx and Sly has led to a runaway "arms race" between the chromosomes that drives massive amplification of competing X / Y gene complexes, and also of any autosomal loci embroiled in the conflict. The signs of this conflict have now been observed at the molecular genetic level in the form of opposing transcriptional regulatory consequences of Slx / Sly depletion [4,[9][10][11]13,14]; at the cellular biological level in the form of Slx / Sly competition for intracellular binding targets [14][15][16][17]; at the organism level in the form of sex ratio skewing in Yq-deleted animals, transgenic Slx / Sly knockdown animals and various Y chromosome congenic males [3,5,6,11,18]; at the ecological level in the form of population sex ratio skewing in introgression zones between subspecies with different copy numbers of the Yborne amplicons [19,20]; and at the evolutionary population genetic level in the form of correlated co-amplification of gene families and recurrent selective sweeps at X and Y-linked amplicons [13,[21][22][23][24][25].…”

“…Previous efforts in this direction have concentrated on identifying differences between Yqdeleted males and normal controls, revealing defects in acrosome biogenesis, sperm morphology and motility, in vitro fertilising ability, chromatin condensation of epididymal sperm, protease activity in the sperm head, and curiously an increase in progesterone production in the cumulus cells of daughters of affected males [3,[5][6][7][26][27][28][29][30][31][32][33][34][35]. However, these analyses only give information about the global effects of Yq gene deficiency, and do not address the issue of differential effects on X-and Y-bearing sperm that mediate sex ratio skewing.…”

Differential Sperm Motility Mediates the Sex Ratio Drive Shaping Mouse Sex Chromosome Evolution

“…The sex-linked ampliconic transcriptional regulators Slx and Sly [3, 4, 5, 6, 7] have opposing effects on global transcription levels of the sex chromosomes in haploid spermatids via regulation of postmeiotic sex chromatin (PMSC) [8, 9, 10, 11] and opposing effects on offspring sex ratio. Partial deletions of the Y chromosome (Yq) that reduce Sly copy number lead to global overexpression of sex-linked genes in spermatids and either a distorted sex ratio in favor of females (smaller deletions) or sterility (larger deletions) [12, 13, 14, 15, 16]. Despite a large body of work studying the role of the sex chromosomes in regulating spermatogenesis (recent reviews [17, 18, 19, 20]), most studies do not address differential fertility effects on X- and Y-bearing cells.…”