MSH2 shapes the meiotic crossover landscape in relation to interhomolog polymorphism in Arabidopsis.
MSH2 shapes the meiotic crossover landscape in relation to interhomolog polymorphism in Arabidopsis.
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DOI：
10.15252/embj.2020104858
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发表时间：
2020-11-02
期刊：
影响因子：
--
通讯作者：
Henderson IR
中科院分区：
文献类型：
--
作者：
Blackwell AR;Dluzewska J;Szymanska-Lejman M;Desjardins S;Tock AJ;Kbiri N;Lambing C;Lawrence EJ;Bieluszewski T;Rowan B;Higgins JD;Ziolkowski PA;Henderson IR
在减数分裂过程中，DNA双链断裂经历同源修复，从而在同源染色体之间产生交叉。为了研究同源序列间的多态如何影响杂交，我们对模式植物拟南芥的多个重组群体进行了测序。在不同的着丝粒周围区域，交叉点升高，显示出对多态区域的局部偏好。我们提供的证据表明，与提高的多样性的交叉关联是通过I类交叉形成途径调节的，尽管非常高的多样性水平抑制了交叉。同源基因间的多态性导致重组分子中的错配，这可以通过MutS同源错配修复蛋白异源二聚体来检测。因此，我们使用多个杂交背景，在错配识别缺陷的MSH2突变体中定位了交叉。虽然msh2突变体的总交叉数没有变化，但重组从不同的着丝粒周围向多态较少的亚端粒区域重塑。在野生型拟南芥中，百万碱基杂合区和纯合区的并置导致向杂合区的交叉重塑，但在MSH2突变体中不是。免疫染色显示，在减数分裂前期I，MSH2蛋白在减数分裂染色体上积累，与MSH2调控减数分裂重组一致。我们的结果揭示了MSH2在拟南芥中序列多样性较高的区域中的亲交叉作用。对野生型和突变型植物同源染色体之间的多态进行测序表明，错配修复蛋白MSH2在相对序列多样性较高的区域具有意想不到的促进交叉作用。
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 MSH2 protein accumulates on meiotic chromosomes during prophase I, consistent with MSH2 regulating meiotic recombination. Our results reveal a pro‐crossover role for MSH2 in regions of higher sequence diversity in A. thaliana. Sequencing of polymorphisms between homologous chromosomes in wild‐type and mutant plants reveals an unexpected pro‐crossover role of the mismatch repair protein MSH2 in regions of higher relative sequence diversity.
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