Mechanistic Insight into Crossing over during Mouse Meiosis

Peterson, Shaun; Keeney, Scott; Jasin, Maria

doi:10.1016/j.molcel.2020.04.009

“…For example, crossover frequency measured at varying scales in mice did not change in msh2 or pms2 (Qin et al, 2002;Kolas et al, 2005;Peterson et al, 2020). Mouse msh2 mutants show heteroduplex retention in crossover products, but MSH2-dependent suppression of meiotic recombination was not observed (Peterson et al, 2020). Interestingly, this is in contrast to the anti-recombination role of MSH2 in mitotic cells observed during HR in both mouse and Arabidopsis (Elliott & Jasin, 2001;Emmanuel et al, 2006;Li et al, 2006).…”

Section: Of 22mentioning

confidence: 78%

“…Finally, we note that msh2 meiotic recombination phenotypes differ between other species. For example, crossover frequency measured at varying scales in mice did not change in msh2 or pms2 (Qin et al, 2002;Kolas et al, 2005;Peterson et al, 2020). Mouse msh2 mutants show heteroduplex retention in crossover products, but MSH2-dependent suppression of meiotic recombination was not observed (Peterson et al, 2020).…”

Section: Of 22mentioning

confidence: 95%

MSH 2 shapes the meiotic crossover landscape in relation to interhomolog polymorphism in Arabidopsis

Blackwell

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Dluzewska

²

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Szymanska-Lejman

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et al. 2020

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During meiosis, DNA double‐strand breaks undergo interhomolog repair to yield crossovers between homologous chromosomes. To investigate how interhomolog sequence polymorphism affects crossovers, we sequenced multiple recombinant populations of the model plant Arabidopsis thaliana . Crossovers were elevated in the diverse pericentromeric regions, showing a local preference for polymorphic regions. We provide evidence that crossover association with elevated diversity is mediated via the Class I crossover formation pathway, although very high levels of diversity suppress crossovers. Interhomolog polymorphism causes mismatches in recombining molecules, which can be detected by MutS homolog (MSH) mismatch repair protein heterodimers. Therefore, we mapped crossovers in a msh2 mutant, defective in mismatch recognition, using multiple hybrid backgrounds. Although total crossover numbers were unchanged in msh2 mutants, recombination was remodelled from the diverse pericentromeres towards the less‐polymorphic sub‐telomeric regions. Juxtaposition of megabase heterozygous and homozygous regions causes crossover remodelling towards the heterozygous regions in wild type Arabidopsis , but not in msh2 mutants. Immunostaining showed that MSH 2 protein accumulates on meiotic chromosomes during prophase I, consistent with MSH2 regulating meiotic recombination. Our results reveal a pro‐crossover role for MSH 2 in regions of higher sequence diversity in A. thaliana .

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“…cerevisiae also similarly indicate that even at 26% sequence divergence, loss of MMR leads to a 55-fold increase in mitotic recombination [ 72 , 73 ]. Conversely, studies in other models have observed instances where loss of Msh2 did not lead to increased recombination frequencies between substrates with as little as 1% sequence divergence, up to 25% divergence [ 74 – 76 ].…”

Section: Discussionmentioning

confidence: 99%

Factors enforcing the species boundary between the human pathogens Cryptococcus neoformans and Cryptococcus deneoformans

Priest

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,

Coelho

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,

Mixão

³

et al. 2021

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Hybridization has resulted in the origin and variation in extant species, and hybrids continue to arise despite pre- and post-zygotic barriers that limit their formation and evolutionary success. One important system that maintains species boundaries in prokaryotes and eukaryotes is the mismatch repair pathway, which blocks recombination between divergent DNA sequences. Previous studies illuminated the role of the mismatch repair component Msh2 in blocking genetic recombination between divergent DNA during meiosis. Loss of Msh2 results in increased interspecific genetic recombination in bacterial and yeast models, and increased viability of progeny derived from yeast hybrid crosses. Hybrid isolates of two pathogenic fungal Cryptococcus species, Cryptococcus neoformans and Cryptococcus deneoformans, are isolated regularly from both clinical and environmental sources. In the present study, we sought to determine if loss of Msh2 would relax the species boundary between C. neoformans and C. deneoformans. We found that crosses between these two species in which both parents lack Msh2 produced hybrid progeny with increased viability and high levels of aneuploidy. Whole-genome sequencing revealed few instances of recombination among hybrid progeny and did not identify increased levels of recombination in progeny derived from parents lacking Msh2. Several hybrid progeny produced structures associated with sexual reproduction when incubated alone on nutrient-rich medium in light, a novel phenotype in Cryptococcus. These findings represent a unique, unexpected case where rendering the mismatch repair system defective did not result in increased meiotic recombination across a species boundary. This suggests that alternative pathways or other mismatch repair components limit meiotic recombination between homeologous DNA and enforce species boundaries in the basidiomycete Cryptococcus species.

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“…Furthermore, studies on mitotic recombination in S. cerevisiae also similarly indicate that even at 26% sequence divergence, loss of MMR leads to a 55-fold increase in mitotic recombination [72,73]. Conversely, studies in other models have observed instances where loss of Msh2 did not lead to increased recombination frequencies between substrates with as little as 1% sequence divergence, up to 25% divergence [74–76].…”

Section: Discussionmentioning

confidence: 99%

Factors enforcing the species boundary between the human pathogensCryptococcus neoformansandCryptococcus deneoformans

Priest

¹

,

Coelho

²

,

Mixão

³

et al. 2020

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Hybridization has resulted in the origin and variation in extant species, and hybrids continue to arise despite pre- and post-zygotic barriers that limit their formation and evolutionary success. One important system that maintains species boundaries in prokaryotes and eukaryotes is the mismatch repair pathway, which blocks homeologous recombination between divergent DNA sequences. Previous studies illuminated the role of the mismatch repair component Msh2 in blocking genetic recombination between divergent DNA during meiosis in yeast and during conjugational and transductional crosses in bacteria. Loss of Msh2 resulted in increased interspecific genetic recombination in bacterial and yeast models, and increased viability of progeny derived from yeast hybrid crosses. Hybrid isolates of two pathogenic fungal Cryptococcus species, Cryptococcus neoformans and Cryptococcus deneoformans, are isolated regularly from both clinical and environmental sources. In the present study, we sought to determine if loss of Msh2 would relax the species boundary between C. neoformans and C. deneoformans. We found that crosses between these two species in which both parents lack Msh2 produced hybrid progeny with increased viability and high levels of aneuploidy. Whole-genome sequencing revealed few instances of recombination among hybrid progeny and did not identify increased levels of recombination in progeny derived from parents lacking Msh2. Several hybrid progeny from bilateral msh2Δ crosses produced structures associated with sexual reproduction when incubated alone on nutrient-rich medium in light, a novel transgressive phenotype in Cryptococcus. These findings represent a unique, unexpected case where rendering the mismatch repair system defective did not result in increased meiotic recombination across a species boundary. This suggests that alternative pathways limit meiotic recombination between homeologous DNA and enforce species boundaries in the basidiomycete Cryptococcus species and possibly in others as well.Author summarySeveral mechanisms enforce species boundaries by either preventing the formation of hybrids, known as pre-zygotic barriers, or preventing the viability and fecundity of hybrids, known as post-zygotic barriers. Despite these barriers, interspecies hybrids form at an appreciable frequency, such as hybrid isolates of the human fungal pathogenic species, Cryptococcus neoformans and Cryptococcus deneoformans, which are regularly isolated from both clinical and environmental sources. C. neoformans x C. deneoformans hybrids are typically highly aneuploid, sterile, and display phenotypes intermediate to those of either parent, although self-fertile isolates and transgressive phenotypes have been observed. One important mechanism known to enforce species boundaries or lead to incipient speciation is the DNA mismatch repair system, which blocks recombination between divergent DNA sequences during meiosis. The aim of this study was to determine if genetically deleting the DNA mismatch repair component Msh2 would relax the species boundary between C. neoformans and C. deneoformans. Progeny derived from C. neoformans x C. deneoformans crosses in which both parental strains lacked Msh2 had higher viability, several progeny displayed a novel transgressive phenotype, and unlike previous studies in Saccharomyces, these Cryptococcus hybrid progeny had higher levels of aneuploidy and no observable increase in meiotic recombination at the whole-genome level.

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Mechanistic Insight into Crossing over during Mouse Meiosis

Cited by 29 publications

References 68 publications

MSH 2 shapes the meiotic crossover landscape in relation to interhomolog polymorphism in Arabidopsis

MSH 2 shapes the meiotic crossover landscape in relation to interhomolog polymorphism in Arabidopsis

Factors enforcing the species boundary between the human pathogens Cryptococcus neoformans and Cryptococcus deneoformans

Factors enforcing the species boundary between the human pathogensCryptococcus neoformansandCryptococcus deneoformans

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