Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, Madrid, Spain.
Institut des Sciences de l'Evolution, ISEM UMR 5554 (CNRS/Université Montpellier/IRD/EPHE), Montpellier, France.
PLoS Genet. 2020 Nov 12;16(11):e1008959. doi: 10.1371/journal.pgen.1008959. eCollection 2020 Nov.
Sex chromosomes of eutherian mammals are highly different in size and gene content, and share only a small region of homology (pseudoautosomal region, PAR). They are thought to have evolved through an addition-attrition cycle involving the addition of autosomal segments to sex chromosomes and their subsequent differentiation. The events that drive this process are difficult to investigate because sex chromosomes in almost all mammals are at a very advanced stage of differentiation. Here, we have taken advantage of a recent translocation of an autosome to both sex chromosomes in the African pygmy mouse Mus minutoides, which has restored a large segment of homology (neo-PAR). By studying meiotic sex chromosome behavior and identifying fully sex-linked genetic markers in the neo-PAR, we demonstrate that this region shows unequivocal signs of early sex-differentiation. First, synapsis and resolution of DNA damage intermediates are delayed in the neo-PAR during meiosis. Second, recombination is suppressed or largely reduced in a large portion of the neo-PAR. However, the inactivation process that characterizes sex chromosomes during meiosis does not extend to this region. Finally, the sex chromosomes show a dual mechanism of association at metaphase-I that involves the formation of a chiasma in the neo-PAR and the preservation of an ancestral achiasmate mode of association in the non-homologous segments. We show that the study of meiosis is crucial to apprehend the onset of sex chromosome differentiation, as it introduces structural and functional constrains to sex chromosome evolution. Synapsis and DNA repair dynamics are the first processes affected in the incipient differentiation of X and Y chromosomes, and they may be involved in accelerating their evolution. This provides one of the very first reports of early steps in neo-sex chromosome differentiation in mammals, and for the first time a cellular framework for the addition-attrition model of sex chromosome evolution.
真兽类哺乳动物的性染色体在大小和基因含量上差异很大，仅共享一小段同源区（假常染色体区，PAR）。它们被认为是通过涉及添加常染色体片段到性染色体及其随后分化的添加-损耗循环进化而来的。由于几乎所有哺乳动物的性染色体都处于非常分化的阶段，因此很难研究驱动这一过程的事件。在这里，我们利用非洲小囊鼠 Mus minutoides 中最近发生的一次常染色体易位到两条性染色体上的情况，该易位恢复了一大段同源区（新 PAR）。通过研究减数分裂中性染色体的行为并在新 PAR 中鉴定出完全性连锁的遗传标记，我们证明该区域表现出明确的早期性别分化迹象。首先，在减数分裂过程中，新 PAR 中的联会和 DNA 损伤中间体的解决会延迟。其次，重组在新 PAR 的大部分区域被抑制或大大减少。然而，减数分裂中特征性染色体的失活过程不会扩展到该区域。最后，性染色体在中期 I 表现出双重关联机制，涉及新 PAR 中形成交叉和非同源片段中保持原始的无交叉关联模式。我们表明，减数分裂的研究对于理解性染色体分化的开始至关重要，因为它为性染色体进化带来了结构和功能限制。联会和 DNA 修复动力学是 X 和 Y 染色体初步分化中首先受到影响的过程，它们可能参与加速它们的进化。这提供了哺乳动物中新性染色体分化的早期步骤的第一个报告之一，并且首次为性染色体进化的添加-损耗模型提供了一个细胞框架。
