Sex chromosome quadrivalents in oocytes of the African pygmy mouse Mus minutoides that harbors non-conventional sex chromosomes

Abstract

Eutherian mammals have an extremely conserved sex-determining system controlled by highly differentiated sex chromosomes. Females are XX and males XY, and any deviation generally leads to infertility, mainly due to meiosis disruption. The African pygmy mouse (Mus minutoides) presents an atypical sex determination system with three sex chromosomes: the classical X and Y chromosomes and a feminizing X chromosome variant, called X*. Thus, three types of females coexist (XX, XX*, and X*Y) that all show normal fertility. Moreover, the three chromosomes (X and Y on one side and X* on the other side) are fused to different autosomes, which results in the inclusion of the sex chromosomes in a quadrivalent in XX* and X*Y females at meiotic prophase. Here, we characterized the configurations adopted by these sex chromosome quadrivalents during meiotic prophase. The XX* quadrivalent displayed a closed structure in which all homologous chromosome arms were fully synapsed and with sufficient crossovers to ensure the reductional segregation of all chromosomes at the first meiotic division. Conversely, the X*Yquadrivalents adopted either a closed configuration with non-homologous synapsis of the X* and Y chromosomes or an open chain configuration in which X* and Y remained asynapsed and possibly transcriptionally silenced. Moreover, the number of crossovers was insufficient to ensure chromosome segregation in a significant fraction of nuclei. Together, these findings raise questions about the mechanisms allowing X*Y females to have a level of fertility as good as that of XX and XX* females, if not higher.

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

“…The length of the neo-PAR, the extreme size difference of the non-homologous segments of the X and Y chromosomes and the fact that all chromosome ends remain attached to the nuclear envelope force the X chromosome to bend significantly (see Fig 2F), which may be the cause of the synapsis delay, as has been reported for other chromosomal rearrangements [70,71]. Furthermore, other type of synapsis impairments have been described in other mammalian species with neo-sex chromosomes (e.g., heterologous synapsis, asynapsis, desynapsis) [20,[72][73][74]. Such modifications seem to be the norm following sex-autosome fusions in mammals.…”

“…Given this context, we propose that synapsis in the proximal region of the neo-PAR observed at late pachytene in M. minutoides may already be heterologous ( Fig 6) and, therefore, this region would be no longer be considered part of the neo-PAR. In line with this proposal, the proximal region of the Y neo-PAR usually engages in heterologous synapsis with other chromosomes during XY female meiosis [72]. The fact that the neo-PAR is still able to complete synapsis in male meiosis could be due to a process known as synaptic adjustment that is typical in the non-homologous regions of the X and Y chromosomes in most mammals [15,32,36,87].…”

“…The population studied here, coming from the Caledon Nature Reserve in South Africa, has a diploid number of 2n = 18 and all chromosomes are metacentric. In males, the sex chromosome pair is composed of (i) non-homologous arms, formed by the completely differentiated (achiasmate) "ancestral" sex chromosomes that differ in length, and (ii) homologous arms, formed by ancestral chromosome 1 (hereafter, the neo-PAR) that are homomorphic in length and in their G- [50,72]. The sex bivalent is largely heteromorphic in the non-homologous segments.…”

“…This feminizing X is also fused to chromosome 1 in the majority of M. minutoides populations and may show recombination in the neo-PAR. However, Baudat et al [72] recently investigated M. minutoides meiosis in XY females and they reported that the proximal segment of the neo-PAR of the Y chromosome is always involved in heterologous synapsis (with no MLH1 foci). Consistent with our RAD-seq analyses, their results strongly suggest that recombination is also highly reduced or suppressed in the proximal segment of the neo-PAR in XY females.…”

Special issue on “recent advances in meiosis from DNA replication to chromosome segregation”

“…They find that these chromosomes adopt a quadrivalent structure with evidence suggesting transcriptional silencing of unsynapsed chromosomes. Intriguingly, despite similar levels of fertility between XX, XX*, and X*Y oocytes, the X*Y quadrivalents have too few crossing over events to account for the accurate segregation observed, suggesting alternate achiasmate segregation mechanisms in this species (Baudat et al, 2019). On a similar topic, Page and colleagues studied wild mice populations with different Robertsonian translocations, which allow them to establish a direct link between a failure to synapse in the translocated regions and a defect in DSB repair in these regions.…”