Valero-Regalón F Javier, Solé Mireia, López-Jiménez Pablo, Valerio-de Arana María, Martín-Ruiz Marta, de la Fuente Roberto, Marín-Gual Laia, Renfree Marilyn B, Shaw Geoff, Berríos Soledad, Fernández-Donoso Raúl, Waters Paul D, Ruiz-Herrera Aurora, Gómez Rocío, Page Jesús
Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, Madrid, Spain.
Genetics of Male Fertility Group, Unitat de Biologia Cel·lular, Universitat Autònoma de Barcelona, Spain.
Front Cell Dev Biol. 2023 Apr 25;11:1147610. doi: 10.3389/fcell.2023.1147610. eCollection 2023.
In eutherian mammals, hundreds of programmed DNA double-strand breaks (DSBs) are generated at the onset of meiosis. The DNA damage response is then triggered. Although the dynamics of this response is well studied in eutherian mammals, recent findings have revealed different patterns of DNA damage signaling and repair in marsupial mammals. To better characterize these differences, here we analyzed synapsis and the chromosomal distribution of meiotic DSBs markers in three different marsupial species (, and ) that represent South American and Australian Orders. Our results revealed inter-specific differences in the chromosomal distribution of DNA damage and repair proteins, which were associated with differing synapsis patterns. In the American species and chromosomal ends were conspicuously polarized in a configuration and synapsis progressed exclusively from the telomeres towards interstitial regions. This was accompanied by sparse H2AX phosphorylation, mainly accumulating at chromosomal ends. Accordingly, RAD51 and RPA were mainly localized at chromosomal ends throughout prophase I in both American marsupials, likely resulting in reduced recombination rates at interstitial positions. In sharp contrast, synapsis initiated at both interstitial and distal chromosomal regions in the Australian representative , the polarization was incomplete and ephemeral, γH2AX had a broad nuclear distribution, and RAD51 and RPA foci displayed an even chromosomal distribution. Given the basal evolutionary position of , it is likely that the meiotic features reported in this species represent an ancestral pattern in marsupials and that a shift in the meiotic program occurred after the split of and the Australian marsupial clade. Our results open intriguing questions about the regulation and homeostasis of meiotic DSBs in marsupials. The low recombination rates observed at the interstitial chromosomal regions in American marsupials can result in the formation of large linkage groups, thus having an impact in the evolution of their genomes.
在真兽亚纲哺乳动物中，减数分裂开始时会产生数百个程序性DNA双链断裂（DSB）。随后会触发DNA损伤反应。尽管在真兽亚纲哺乳动物中对这种反应的动态过程已有充分研究，但最近的研究结果揭示了有袋类哺乳动物中DNA损伤信号传导和修复的不同模式。为了更好地描述这些差异，我们在此分析了代表南美洲和澳大利亚目三个不同有袋类物种（ 、 和 ）减数分裂DSB标记的联会情况和染色体分布。我们的结果揭示了DNA损伤和修复蛋白在染色体分布上的种间差异，这些差异与不同的联会模式相关。在美洲物种 和 中，染色体末端明显呈 构型极化，联会仅从端粒向间质区域推进。这伴随着稀疏的H2AX磷酸化，主要积累在染色体末端。因此，在这两种美洲有袋类动物的整个减数分裂前期I中，RAD51和RPA主要定位于染色体末端，这可能导致间质位置的重组率降低。与之形成鲜明对比的是，在澳大利亚代表物种 中，联会在染色体间质和远端区域均起始， 极化不完整且短暂，γH2AX具有广泛的核分布，RAD51和RPA焦点呈现均匀的染色体分布。鉴于 的基础进化地位，该物种中报道的减数分裂特征可能代表有袋类动物的祖先模式，并且在 和澳大利亚有袋类进化枝分裂后减数分裂程序发生了转变。我们的结果引发了关于有袋类动物减数分裂DSB调控和稳态的有趣问题。在美洲有袋类动物的染色体间质区域观察到的低重组率可能导致形成大的连锁群，从而对其基因组的进化产生影响。
