Meiotic Consequences of Genetic Divergence Across the Murine Pseudoautosomal Region

Dumont, Beth L.

doi:10.1534/genetics.116.189092

Cited by 18 publications

(23 citation statements)

References 73 publications

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“…This 100-fold elevation of the recombination rate in the CAST/EiJ extended PAR over the autosomal background is consistent with obligatory crossing-over in the PAR at every meiosis (Burgoyne 1982) despite its relatively small physical size (Perry et al 2001). We find no evidence for transmission bias against recombinants (pooled OR from both crosses = 0.89 by logistic regression, 95% CI 0.44 — 1.82, p = 0.75 by likelihood-ratio test), and a rate of sex-chromosome nondisjunction (XOs: 1/267,0.37%) similar to prior estimates for these F1s (Dumont 2017).…”

Section: Resultssupporting

confidence: 62%

“…Finally, we uncover a remarkable degree of polymorphism at and likely across the PAR boundary in natural populations of all three subspecies. These findings add to a growing body of evidence that the degree of homology required for male fertility is relatively weak (Dumont 2017; Acquaviva et al 2019). Relaxed constraint on PAR structure, combined with the intensity of double-strand break activity in male meiosis, permit the generation and maintenance of unusual levels of diversity in this peculiar region of the sex chromosomes.…”

Section: Introductionsupporting

confidence: 62%

“…Our findings support the notion that the requirement for structural homology in the PAR is relatively weak in mice. Dumont (2017) has shown that although the number of X-Y crossovers (assayed by immunostaining against the MLH1 protein) in inter-subspecific F1 hybrid males is reduced relative to the parental strains, absence of stable X-Y pairing is pervasive in both inbreds and F1s. Failure to pair the sex chromosomes is associated with meiotic arrest and subsequent apoptosis of up to 80% of spermatocytes in some inter-subspecific hybrids – but also up to 25% of spermatocytes in some inbred strains (Imai et al 1981; Krzanowska 1989; Mat-suda et al 1992; Dumont 2017).…”

Section: Discussionmentioning

confidence: 99%

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Instability of the pseudoautosomal boundary in house mice

Morgan

Bell

Crowley

et al. 2019

Preprint

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17Faithful segregation of homologous chromosomes at meiosis requires pairing and recombination. In taxa 18 with dimorphic sex chromosomes, pairing between them in the heterogametic sex is limited to a narrow inter-19 val of residual sequence homology known as the pseudoautosomal region (PAR). Failure to form the obligate 20 crossover in the PAR is associated with male infertility in house mice (Mus musculus) and humans. Yet despite 21 this apparent functional constraint, the boundary and organization of the PAR is highly variable in mammals, 22 and even between subspecies of mice. Here we estimate the genetic map in a previously-documented ex-23 pansion of the PAR in the Mus musculus castaneus subspecies and show that the local recombination rate is 24 100-fold higher than the autosomal background. We identify an independent shift in the PAR boundary in the 25 Mus musculus musculus subspecies and show that it involves a complex rearrangement but still recombines in 26 heterozygous males. Finally, we demonstrate pervasive copy-number variation at the PAR boundary in wild 27 populations of M. m. domesticus, M. m. musculus and M. m. castaneus. Our results suggest that the intensity of 28 recombination activity in the PAR, coupled with relatively weak constraints on its sequence, permit the genera-29 tion and maintenance in the population of unusual levels of polymorphism of unknown functional significance. 30 31Pairing, synapsis and crossing-over between homologous chromosomes is a requirement for orderly progres-34 sion through meiosis that is broadly conserved in eukaryotes (Mather 1938; Mirzaghaderi and Hörandl 2016). 35In most organisms, pairing is facilitated by sequence homology. The sex chromosomes of mammals -which 36 are divergent in sequence and structure over most of their length (Graves 2006) -thus pose a unique challenge 37 for males, the heterogametic sex. Homology between the X and Y is limited to remnant "pseudoautosomal 38 regions" (PARs) that are a vestige of the sex chromosomes' origin as an ancestral autosome pair (Ohno 1966). 39Synapsis and crossing-over in this relatively small territory appears to be necessary for faithful segregation of 40

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Section: Resultssupporting

confidence: 62%

Section: Introductionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

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Instability of the pseudoautosomal boundary in house mice

Morgan

Bell

Crowley

et al. 2019

Preprint

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“…The critical meiotic activities of pairing, synapsis, and crossing over are concentrated to this narrow interval (Burgoyne 1982), rendering the PAR the most recombinogenic locus in the mammalian genome (Rouyer et al 1986;Page et al 1987;Hinch et al 2014). In most mammals, disruption of sequence homology between X-and Y-linked PAR sequences can trigger meiotic metaphase I arrest and apoptosis (Gabriel-Robez et al 1990;Burgoyne et al 1992;Mohandas et al 1992;Dumont 2017). PAR-spanning mutations may even provide a barrier to gene flow between incipient species (White et al 2012a,b).…”

mentioning

confidence: 99%

Relationship Between Sequence Homology, Genome Architecture, and Meiotic Behavior of the Sex Chromosomes in North American Voles

Dumont

Williams

et al. 2018

Genetics

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In most mammals, the X and Y chromosomes synapse and recombine along a conserved region of homology known as the pseudoautosomal region (PAR). These homology-driven interactions are required for meiotic progression and are essential for male fertility. Although the PAR fulfills key meiotic functions in most mammals, several exceptional species lack PAR-mediated sex chromosome associations at meiosis. Here, we leveraged the natural variation in meiotic sex chromosome programs present in North American voles () to investigate the relationship between meiotic sex chromosome dynamics and X/Y sequence homology. To this end, we developed a novel, reference-blind computational method to analyze sparse sequencing data from flow-sorted X and Y chromosomes isolated from vole species with sex chromosomes that always (), never (), and occasionally synapse () at meiosis. Unexpectedly, we find more shared X/Y homology in the two vole species with no and sporadic X/Y synapsis compared to the species with obligate synapsis. Sex chromosome homology in the asynaptic and occasionally synaptic species is interspersed along chromosomes and largely restricted to low-complexity sequences, including a striking enrichment for the telomeric repeat sequence, TTAGGG. In contrast, homology is concentrated in high complexity, and presumably euchromatic, sequence on the X and Y chromosomes of the synaptic vole species, Taken together, our findings suggest key conditions required to sustain the standard program of X/Y synapsis at meiosis and reveal an intriguing connection between heterochromatic repeat architecture and noncanonical, asynaptic mechanisms of sex chromosome segregation in voles.

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“…First, current theory does not predict whether inversions tying together sexually antagonistic loci and sex chromosomes should preferentially occur on the X or Y chromosome. Second, theory has ignored the necessity of a recombining region in species with chiasmatic meiosis—as recombination suppression spreads across sex chromosomes, the region available for meiotic pairing of sex chromosomes in the heterogametic sex becomes small, likely creating problems during male meiosis ( Dumont 2017a ). The theory we develop below addresses these questions.…”

mentioning

confidence: 99%