Association of Sly with sex-linked gene amplification during mouse evolution: a side effect of genomic conflict in spermatids?

Ellis, Peter J. I.; Bacon, Joanne; Affara, Nabeel A.

doi:10.1093/hmg/ddr204

Cited by 61 publications

(109 citation statements)

References 36 publications

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“…Sly genes are estimated to be present in between 70 and 100 copies in the mouse genome; the majority of these encode two transcript splice variants, Sly1 and Sly2 Ellis et al, 2011;Scavetta and Tautz, 2010). In the present study, we have produced and characterized a Sly1-only-deficient mouse model, and shown that, in contrast to Sly-deficient mice, in which both transcript variants are affected, Sly1-only-deficient mice do not have sperm differentiation defects.…”

Section: Discussionmentioning

confidence: 68%

Deficiency of the multi-copy mouse Y gene Sly causes sperm DNA damage and abnormal chromatin packaging

Riel

Yamauchi

Sugawara

et al. 2012

Journal of Cell Science

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SummaryIn mouse and man Y chromosome deletions are frequently associated with spermatogenic defects. Mice with extensive deletions of nonpairing Y chromosome long arm (NPYq) are infertile and produce sperm with grossly misshapen heads, abnormal chromatin packaging and DNA damage. The NPYq-encoded multi-copy gene Sly controls the expression of sex chromosome genes after meiosis and Sly deficiency results in a remarkable upregulation of sex chromosome genes. Sly deficiency has been shown to be the underlying cause of the sperm head anomalies and infertility associated with NPYq gene loss, but it was not known whether it recapitulates sperm DNA damage phenotype. We produced and examined mice with transgenically (RNAi) silenced Sly and demonstrated that these mice have increased incidence of sperm with DNA damage and poorly condensed and insufficiently protaminated chromatin. We also investigated the contribution of each of the two Sly-encoded transcript variants and noted that the phenotype was only observed when both variants were knocked down, and that the phenotype was intermediate in severity compared with mice with severe NPYq deficiency. Our data demonstrate that Sly deficiency is responsible for the sperm DNA damage/chromatin packaging defects observed in mice with NPYq deletions and point to SLY proteins involvement in chromatin reprogramming during spermiogenesis, probably through their effect on the post-meiotic expression of spermiogenic genes. Considering the importance of the sperm epigenome for embryonic and fetal development and the possibility of its inter-generational transmission, our results are important for future investigations of the molecular mechanisms of this biologically and clinically important process.

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Section: Discussionmentioning

confidence: 68%

Deficiency of the multi-copy mouse Y gene Sly causes sperm DNA damage and abnormal chromatin packaging

Riel

Yamauchi

Sugawara

et al. 2012

Journal of Cell Science

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“…In line with this conjecture, correlated gene amplification in mouse between sexually antagonistic X-linked Slx genes and Y-linked Sly genes in rodents has been suggested to be a consequence of intragenomic conflict between X and Y chromosomes to balance the sex ratio (33)(34)(35). A recent report in mouse also suggests that amplification of Y-linked ampliconic genes is driven by the gene amplification of the gametologous X-linked gene pairs to restore an optimal sex ratio (36).…”

Section: Discussionmentioning

confidence: 82%

Extreme selective sweeps independently targeted the X chromosomes of the great apes

Nam¹,

Dutheil

Schierup

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The unique inheritance pattern of the X chromosome exposes it to natural selection in a way that is different from that of the autosomes, potentially resulting in accelerated evolution. We perform a comparative analysis of X chromosome polymorphism in 10 great ape species, including humans. In most species, we identify striking megabase-wide regions, where nucleotide diversity is less than 20% of the chromosomal average. Such regions are found exclusively on the X chromosome. The regions overlap partially among species, suggesting that the underlying targets are partly shared among species. The regions have higher proportions of singleton SNPs, higher levels of population differentiation, and a higher nonsynonymous-to-synonymous substitution ratio than the rest of the X chromosome. We show that the extent to which diversity is reduced is incompatible with direct selection or the action of background selection and soft selective sweeps alone, and therefore, we suggest that very strong selective sweeps have independently targeted these specific regions in several species. The only genomic feature that we can identify as strongly associated with loss of diversity is the location of testis-expressed ampliconic genes, which also have reduced diversity around them. We hypothesize that these genes may be responsible for selective sweeps in the form of meiotic drive caused by an intragenomic conflict in male meiosis. X-chromosome evolution | great apes | selective sweeps | ampliconic genes | meiotic drive

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“…Thus, the ratio of Slx/Slxl1 to Sly gene copies is unbalanced in hybrids, and sterile F 1 males with a musculus PWK X and domesticus LEWES Y are potentially Sly deficient. Given phenotypic similarities between sterile F 1 hybrids and Sly-deficient lab mice (i.e., X overexpression and sperm abnormalities), Cocquet and colleagues proposed that Slx/Slxl1:Sly copy number imbalance contributes to hybrid male sterility in the musculus PWK · domesticus LEWES cross (Cocquet et al 2012; see also Ellis et al 2011). Unfortunately, the distribution of musculus-vs. domesticus-derived Sly, Slx, and Slxl1 genotypes among the X introgression F 1 's used in this study precludes a statistical test for the effect of copy number imbalance on X expression: only genotype 7 carries the mismatch between musculus-derived Slx and Slxl1 and domesticus-derived Sly (Figure 2A).…”

Section: Postmeiotic Overexpressionmentioning

confidence: 99%

“…The M. m. musculus X and Y carry at least twice as many copies of Slx/Slxl1 and Sly, respectively, as the M. m. domesticus X and Y (Scavetta and Tautz 2010;Ellis et al 2011). Thus, the ratio of Slx/Slxl1 to Sly gene copies is unbalanced in hybrids, and sterile F 1 males with a musculus PWK X and domesticus LEWES Y are potentially Sly deficient.…”

Section: Postmeiotic Overexpressionmentioning

confidence: 99%

Meiotic Sex Chromosome Inactivation Is Disrupted in Sterile Hybrid Male House Mice

2013

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In male mammals, the X and Y chromosomes are transcriptionally silenced in primary spermatocytes by meiotic sex chromosome inactivation (MSCI) and remain repressed for the duration of spermatogenesis. Here, we test the longstanding hypothesis that disrupted MSCI might contribute to the preferential sterility of heterogametic hybrid males. We studied a cross between wildderived inbred strains of Mus musculus musculus and M. m. domesticus in which sterility is asymmetric: F 1 males with a M. m. musculus mother are sterile or nearly so while F 1 males with a M. m. domesticus mother are normal. In previous work, we discovered widespread overexpression of X-linked genes in the testes of sterile but not fertile F 1 males. Here, we ask whether this overexpression is specifically a result of disrupted MSCI. To do this, we isolated cells from different stages of spermatogenesis and measured the expression of several genes using quantitative PCR. We found that X overexpression in sterile F 1 primary spermatocytes is coincident with the onset of MSCI and persists in postmeiotic spermatids. Using a series of recombinant X genotypes, we then asked whether X overexpression in hybrids is controlled by cis-acting loci across the X chromosome. We found that it is not. Instead, one large interval in the proximal portion of the M. m. musculus X chromosome is associated with both overexpression and the severity of sterility phenotypes in hybrids. These results demonstrate a strong association between X-linked hybrid male sterility and disruption of MSCI and suggest that transacting loci on the X are important for the transcriptional regulation of the X chromosome during spermatogenesis. FORTY years ago, Lifschytz and Lindsley (1972) proposed the provocative hypothesis that the X chromosome is inactivated during male meiosis and that disruption of this process could lead to sterility. The idea that failure of meiotic sex chromosome inactivation (MSCI) might cause sterility is significant in speciation genetics since it provides a possible explanation for the widespread observation that in crosses between species, sterility typically appears first in the heterogametic sex (Haldane 1922;Forejt 1996;Presgraves 2008).Whether MSCI takes place in Drosophila has been debated for several decades (Kremer et al. 1986;McKee and Handel 1993;Hense et al. 2007;Vibranovski et al. 2009). Current evidence suggests that expression on the X chromosome is suppressed relative to the autosomes during spermatogenesis but that this suppression precedes meiosis and thus does not reflect MSCI (Meiklejohn et al. 2011; but see Vibranovski et al. 2012). Likewise, the sex chromosomes are not differentially silenced in chicken oocytes (Guioli et al. 2012). Therefore, failed MSCI cannot explain hybrid sterility in all female-heterogametic taxa. In therian mammals, however, MSCI is well established (Solari 1974;McKee and Handel 1993;Namekawa et al. 2007). Although no MSCI-essential loci have been found on the sex chromosomes, many of the autosomal genes t...

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Association of Sly with sex-linked gene amplification during mouse evolution: a side effect of genomic conflict in spermatids?

Cited by 61 publications

References 36 publications

Deficiency of the multi-copy mouse Y gene Sly causes sperm DNA damage and abnormal chromatin packaging

Deficiency of the multi-copy mouse Y gene Sly causes sperm DNA damage and abnormal chromatin packaging

Extreme selective sweeps independently targeted the X chromosomes of the great apes

Meiotic Sex Chromosome Inactivation Is Disrupted in Sterile Hybrid Male House Mice

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