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.

Eutherian哺乳动物的性染色体在大小和基因含量上有很大差异，并且只共享一小部分同源区域（伪常染色体区域，PAR）。据认为，它们是通过累加循环而进化的，该循环涉及将常染色体片段添加到性染色体上并随后分化。由于几乎所有哺乳动物的性染色体都处于分化的晚期，因此很难调查导致该过程的事件。在这里，我们利用了非洲侏儒鼠Mus minutoides中常染色体向两个性染色体易位的最新优势，已恢复了很大一部分同源性（neo-PAR）。通过研究减数分裂的性染色体行为并在neo-PAR中鉴定完全性相关的遗传标记，我们证明该区域显示出早期性别分化的明确迹象。首先，在减数分裂过程中，neo-PAR中DNA损伤中间体的突触和分解被延迟。其次，在大部分neo-PAR中重组被抑制或大大减少。但是，在减数分裂过程中表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显示出双重结合机制，涉及在neo-PAR中形成chi裂，并在非同源区段中保留祖先八面体的结合模式。我们表明，减数分裂的研究对于了解性染色体分化的发生至关重要，因为它为性染色体的进化引入了结构和功能上的限制。突触和DNA修复动力学是X和Y染色体的早期分化中受影响的第一个过程，并且它们可能参与加速它们的进化。这提供了哺乳动物新性别染色体分化早期步骤的最早报道之一，并且首次提供了性染色体进化加减模型的细胞框架。他们可能会参与加速其发展。这提供了哺乳动物新性别染色体分化早期步骤的最早报道之一，并且首次提供了性染色体进化加减模型的细胞框架。他们可能会参与加速其发展。这提供了哺乳动物新性别染色体分化早期步骤的最早报道之一，并且首次提供了性染色体进化加减模型的细胞框架。