Meiosis reveals the early steps in the evolution of a neo-XY sex chromosome pair in the African pygmy mouse Mus minutoides

Abstract

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.

Evolutionary dynamics of the human pseudoautosomal regions

“…We strongly believe that sexually antagonistic selection and transmission bias are likely to be involved [ 18 , 43 ]. Nevertheless, our results seem to disprove the theory that rare recombination events are enough to prevent genetic differentiation among sex chromosomes [ 44 , 45 ] and, as well, do not support the hypothesis that most PAR genes evolve similarly to autosomal rather than to sex-linked genes (unless recombination is very rare) [ 46 ].…”

Expanding the classical paradigm: what we have learnt from vertebrates about sex chromosome evolution

“…In some cases, a simple system of two sex chromosomes changed into derived systems of three homologous sex chromosomes present in a population, e.g. in the African pygmy mouse Mus minutoides , where sex is determined by typical ancestral X, Y and derived X* causing feminization of X*Y individuals [ 133 ], or in the pipid frog X. tropicalis , in which sex is determined by the combination of Z, W and Y chromosomes [ 134 ], where the masculinizing Y chromosome evolved from the ancestral Z [ 129 ] (case 18 in figure 2 ). A more controversial question is whether sex chromosomes can be totally lost through the transition from GSD to ESD, where there are no consistent sexual differences in genotypes [ 12 ] (case 7 in figure 2 ).…”

“…Another way for material to be added to the system of sex chromosomes is a fusion of the W or more often of the Y (as happened e.g. many times in placental mammals, iguanas and teleosts [143][144][145]) with an autosome, producing multiple neo-sex chromosomes (case 19 in figure 2), where the newly added parts behave as pseudoautosomal regions and can go through subsequent differentiation [133]. Notably, the size of Y and W can be expanded by the accumulation of repetitive sequences [102] (case 11 in figure 2), and repeats from these degenerated chromosomes can 'contaminate' and be amplified on X/Z as well [146,147] (case 12 in figure 2).…”

Meiotic Behavior of Achiasmate Sex Chromosomes in the African Pygmy Mouse Mus mattheyi Offers New Insights into the Evolution of Sex Chromosome Pairing and Segregation in Mammals

“…M. mattheyi [ 51 ] is one of the 18 species of the subgenus Nannomys , with an ancestral-like 2 n = 36 karyotype where all chromosomes are acrocentric, meaning no centric fusions between autosomes nor between sex chromosomes and autosomes [ 52 ]. It was proposed that the X and Y chromosomes of the pygmy mouse species would not share any region of homology and, therefore, could be achiasmate during male meiosis [ 53 , 54 , 55 , 56 , 57 ], but a detailed analysis is lacking. Meiosis has been studied only in another pygmy mouse species, Mus minutoides , which differs to other pygmy mice because in this species a sex-autosome fusion between both the X and the Y and the autosomal pair 1 have restored a large neo-PAR that synapses and recombines at meiosis [ 55 , 57 ].…”