Instability of the pseudoautosomal boundary in house mice

Abstract

17Faithful segregation of homologous chromosomes at meiosis requires pairing and recombination. In taxa 18 with dimorphic sex chromosomes, pairing between them in the heterogametic sex is limited to a narrow inter-19 val of residual sequence homology known as the pseudoautosomal region (PAR). Failure to form the obligate 20 crossover in the PAR is associated with male infertility in house mice (Mus musculus) and humans. Yet despite 21 this apparent functional constraint, the boundary and organization of the PAR is highly variable in mammals, 22 and even between subspecies of mice. Here we estimate the genetic map in a previously-documented ex-23 pansion of the PAR in the Mus musculus castaneus subspecies and show that the local recombination rate is 24 100-fold higher than the autosomal background. We identify an independent shift in the PAR boundary in the 25 Mus musculus musculus subspecies and show that it involves a complex rearrangement but still recombines in 26 heterozygous males. Finally, we demonstrate pervasive copy-number variation at the PAR boundary in wild 27 populations of M. m. domesticus, M. m. musculus and M. m. castaneus. Our results suggest that the intensity of 28 recombination activity in the PAR, coupled with relatively weak constraints on its sequence, permit the genera-29 tion and maintenance in the population of unusual levels of polymorphism of unknown functional significance. 30 31Pairing, synapsis and crossing-over between homologous chromosomes is a requirement for orderly progres-34 sion through meiosis that is broadly conserved in eukaryotes (Mather 1938; Mirzaghaderi and Hörandl 2016). 35In most organisms, pairing is facilitated by sequence homology. The sex chromosomes of mammals -which 36 are divergent in sequence and structure over most of their length (Graves 2006) -thus pose a unique challenge 37 for males, the heterogametic sex. Homology between the X and Y is limited to remnant "pseudoautosomal 38 regions" (PARs) that are a vestige of the sex chromosomes' origin as an ancestral autosome pair (Ohno 1966). 39Synapsis and crossing-over in this relatively small territory appears to be necessary for faithful segregation of 40

The Location of the Pseudoautosomal Boundary in Silene latifolia

“…There are many reasons that make PAR boundary region particularly interesting for evolutionary and molecular genetic studies [ 5 , 62 ]. The genes proximally to PAR boundary do not recombine in male meiosis, while the genes located distally, in the pseudoautosomal region, do recombine and the recombination rate may be unusually high [ 8 ]. How such dramatic difference in the recombination rate in the adjacent regions is determined at the molecular and chromosomal level is not entirely clear.…”

“…Despite the intriguing evolutionary and molecular genetic aspects of the PAR boundary [ 5 ], its location is known only for a few species, including humans [ 66 , 67 ], some mammals [ 68 , 69 , 70 , 71 ], birds [ 2 ] and plants [ 32 , 49 ]. Many of these studies reported the changes in the location of the PAR boundary between closely related species [ 33 , 69 ], or even within a species [ 8 , 32 , 49 ], indicating that the location of the PAR boundary is often unstable and evolutionary labile. In particular, for S. latifolia the PAR boundary was reported to be “fuzzy” [ 49 ], implying that there is a region between the PAR and the sex-linked region where recombination in male meiosis occurs only rarely, and our results are consistent with this.…”

“…As the PAR is partially sex-linked, its properties are intermediate between the sex chromosomes and the autosomes, but they also possess some features unique to these peculiar genomic regions [ 5 ]. In particular, the recombination rate may be unusually high in this region—e.g., in humans the average recombination rate in the p-arm PAR is at least 10 times higher than the genomic average [ 6 , 7 ], while local recombination in mouse PAR is 100 times higher than the genomic average [ 8 ]. This elevated recombination in the PAR is the consequence of X:Y pairing only in this region during male meiosis and the physical size of the region is negatively proportionate to recombination density.…”

“…Moreover, inversions detectable in NRY regions could be the consequence rather than the cause of recombination suppression, as they can occur between the sequences present in multiple copies, such as transposable elements that tend to accumulate in the non-recombining regions [ 30 , 31 ]. The analysis of genes in the region adjacent to the PAR boundary (e.g., [ 8 , 32 , 33 ]) is essential to understand the mechanisms underpinning NRY expansion and shifts in PAR boundary location.…”

Using GC content to compare recombination patterns on the sex chromosomes and autosomes of the guppy,Poecilia reticulata, and its close outgroup species

“…Rather than being an evolutionary consequence of local crossover rates, such 136 correlations might instead reflect a process by which GC content controls crossover rates 137 (Mieczkowski, et al 2006;Liu, et al 2018), or a tendency for GC-rich sequences, including 138 CpG islands to evolve in highly recombinogenic genome regions (Han, et al 2008). However, 139 a region of moderate GC content that was recently transposed into the mouse PAR has been 140 found to experience very frequent recombination, indicating that the recombination rate is 141 not, at least in this case, a consequence of high GC content (Morgan, et al 2019). If the 142 recombination rate is very high in a region, even in just one of the two sexes, it can 143 therefore lead to high GC content, and this evolutionary consequence will be detectable in 144 sequence data from both sexes.…”