Genetic recombination variation in wild Robertsonian mice: on the role of chromosomal fusions andPrdm9allelic background

Abstract

Despite the existence of formal models to explain how chromosomal rearrangements can be fixed in a population in the presence of gene flow, few empirical data are available regarding the mechanisms by which genome shuffling contributes to speciation, especially in mammals. In order to shed light on this intriguing evolutionary process, here we present a detailed empirical study that shows how Robertsonian (Rb) fusions alter the chromosomal distribution of recombination events during the formation of the germline in a Rb system of the western house mouse (Mus musculus domesticus). Our results indicate that both the total number of meiotic crossovers and the chromosomal distribution of recombination events are reduced in mice with Rb fusions and that this can be related to alterations in epigenetic signatures for heterochromatinization. Furthermore, we detected novel house mouse Prdm9 allelic variants in the Rb system. Remarkably, mean recombination rates were positively correlated with a decrease in the number of ZnF domains in the Prdm9 gene. The suggestion that recombination can be modulated by both chromosomal reorganizations and genetic determinants that control the formation of double-stranded breaks during meiosis opens new avenues for understanding the role of recombination in chromosomal speciation.

Reduced recombination patterns in Robertsonian hybrids between chromosomal races of the house mouse: chiasma analyses

“…Comparison of mean chiasma counts between Rb heterozygotes (F1/HYB) and the parental races showed that the mean CN in the former was intermediate, lower than in the St race, and higher than in homozygous Rb mice. Owing to disjunctional constraints of at least one crossover per chromosomal arm for proper segregation (Pardo-Manuel de Villena and Sapienza, 2001), the reduction in CN evidenced in F1 individuals was related to a decrease in the number of multiple chiasmata compared with standard individuals (PardoManuel de Villena and Sapienza, 2001), decrease which was nevertheless less pronounced than that observed in homozygous Rb mice (Dumas and Britton-Davidian, 2002;Capilla et al, 2014). More importantly, female and male F1 hybrids showed chiasma distribution patterns that were significantly different from those in the parental races.…”

“…However, the centromere interference in the F1 generally extended over a smaller chromosomal arm length than in Rb bivalents, and only a distal shift of chiasmata was observed, instead of the more terminal relocation evidenced in Rb mice (Figures 3a and b). The expansion in centromere interference observed in Rb fusions has recently been related to alterations in the epigenetic signatures of heterochromatinization (Capilla et al, 2014).…”

“…To our knowledge, few analyses on chiasma or MLH1 patterns have compared trivalent-carrying heterozygous wild mice with homozygous standard or Rb individuals, and those that have, involve either few cells (that is, 12 cells; Wallace et al, 1992), few Rb fusions (that is, 4; Bidau et al, 2001) or mostly polymorphic hybrid karyotypes (24o2no39; Castiglia and Capanna, 2002;Capilla et al, 2014). The exception is the study by Merico et al (2003) involving other North Italian races (2n ¼ 24, St mice) and their laboratory-bred F1 hybrids (2n ¼ 32 with eight trivalents).…”

“…In the present study, as chiasma values were averaged over all chromosomes, the inter-chromosomal variability could not be assessed. Such data require identification of meiotic chromosomes by specific probes such as FISH-BACs or whole-chromosome probes (Capilla et al, 2014). However, the diversity of rates among races with the same diploid number, as well as among St mice (see for example Tunisia, Italy), strongly suggests that the genetic background also contributes to the recombination landscape (Davisson and Akeson, 1993;Koehler et al, 2002), possibly through the fixation of variant alleles at the Prdm9 gene as suggested by Capilla et al (2014).…”

“…Analyses of recombination rates in wild Rb heterozygotes have also been assessed but involve, in most cases, polymorphic individuals, that is, carrying variable numbers of Rb bivalents and trivalents, making it difficult to disentangle the effect of each meiotic type of configuration (Wallace et al, 1992;Bidau et al, 2001;Castiglia and Capanna, 2002;Capilla et al, 2014). In contrast, extensive analyses of recombination patterns in single-Rb heterozygotes have been performed by genetic assays in crosses between different laboratory strains (Davisson and Akeson, 1993).…”