Are ribosomal DNA clusters rearrangement hotspots? A case study in the genus Mus (Rodentia, Muridae)

<p>Abstract</p> <p>Background</p> <p>Recent advances in comparative genomics have considerably improved our knowledge of the evolution of mammalian karyotype architecture. One of the breakthroughs was the preferential localization of evolutionary breakpoints in regions enriched in repetitive sequences (segmental duplications, telomeres and centromeres). In this context, we investigated the contribution of ribosomal genes to genome reshuffling since they are generally located in pericentromeric or subtelomeric regions, and form repeat clusters on different chromosomes. The target model was the genus <it>Mus </it>which exhibits a high rate of karyotypic change, a large fraction of which involves centromeres.</p> <p>Results</p> <p>The chromosomal distribution of rDNA clusters was determined by <it>in situ </it>hybridization of mouse probes in 19 species. Using a molecular-based reference tree, the phylogenetic distribution of clusters within the genus was reconstructed, and the temporal association between rDNA clusters, breakpoints and centromeres was tested by maximum likelihood analyses. Our results highlighted the following features of rDNA cluster dynamics in the genus <it>Mus</it>: i) rDNA clusters showed extensive diversity in number between species and an almost exclusive pericentromeric location, ii) a strong association between rDNA sites and centromeres was retrieved which may be related to their shared constraint of concerted evolution, iii) 24% of the observed breakpoints mapped near an rDNA cluster, and iv) a substantial rate of rDNA cluster change (insertion, deletion) also occurred in the absence of chromosomal rearrangements.</p> <p>Conclusions</p> <p>This study on the dynamics of rDNA clusters within the genus <it>Mus </it>has revealed a strong evolutionary relationship between rDNA clusters and centromeres. Both of these genomic structures coincide with breakpoints in the genus <it>Mus</it>, suggesting that the accumulation of a large number of repeats in the centromeric region may contribute to the high level of chromosome repatterning observed in this group. However, the elevated rate of rDNA change observed in the chromosomally invariant clade indicates that the presence of these sequences is insufficient to lead to genome instability. In agreement with recent studies, these results suggest that additional factors such as modifications of the epigenetic state of DNA may be required to trigger evolutionary plasticity.</p

Effet des fusions Robertsoniennes sur la recombinaison et conséquences évolutives (approche cytologique par l'analyse des chiasmas chez la souris domestique)

MONTPELLIER-BU Sciences (341722106) / SudocPARIS-Museum-Bib zoologie mam. (751052312) / SudocSudocFranceF

Does chromosomal change restrict gene flow between house mouse populations (Mus musculus domesticus)? Evidence from microsatellite polymorphisms

International audienceChromosomal change is recognized as an important force in speciation-with-gene-flow models. Although Robertsonian (Rb) translocations contribute to hybrid unfitness and modify recombination patterns, they are generally not considered as efficient as inversions in reducing gene flow. The present study analyses two hybridizing chromosomal races of the house mouse (Mus musculus domesticus), one carrying nine Rb fusions (2n = 22) and the other carrying the ancestral karyotype (2n = 40). Chromosomal heterozygosity involves simple meiotic configurations, the underdominance of which is not as efficient in promoting speciation as more complex chromosomal differences. The pattern of divergence between these races was investigated using 32 microsatellite loci distributed over all autosomes. The results highlighted a relatively large differentiation between the two chromosomal races. The contribution of variation in recombination patterns to this differentiation was supported by the contrasting levels of divergence between proximal vs. non-proximal microsatellite loci. Clinal analyses of the Rb fusions through the hybrid zone uncovered differences in steepness between metacentrics, suggesting associated differences in selection which did not involve linked genic incompatibilities. This study illustrates the significant role of Rb-associated changes in recombination in promoting or maintaining divergence between chromosomal races of the house mouse

Is increased chromosomal diversity in house mice from Lombardy (Italy) congruent with genic divergence?

International audienceRecent studies in metacentric (MC) populations of the house mouse, Mus musculus domesticus, singled out underdominance more so than recombination suppression as the foremost barrier to gene flow. Here, MC populations from Lombardy (Italy) were sampled to identify the nature and strength of the barriers to gene flow. The chromosomal analysis recovered the three major MC populations (abbreviated to IBIN, IGAL, both with 2n = 24 and ICRE, 2n = 22), but revealed the existence of a new one (IONE, 2n = 24) which likely derived from IGAL through a single WART (Whole‐Arm Reciprocal Translocation). This, once again, highlights the paramount role of WARTs in the chromosomal diversification of this subspecies. Contacts between MC and standard populations coincided with rivers confirming these hybrid zones as tension zones. Divergence between populations was estimated using available allozyme data. Although the overall low genetic structure globally agreed with the chromosome structure, a large variation in divergence levels was retrieved that only partially matched the underdominance degree. This disparity from expectations highlighted the additional contribution of physical barriers and geographic isolation to the differential rate of evolution of the MC populations of the house mouse

Molecular phylogeny of the genus Mus (Rodentia: Murinae) based on mitochondrial and nuclear data

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Chromosomal polymorphism in mammals: an evolutionary perspective

Although chromosome rearrangements (CRs) are central to studies of genome evolution, our understanding of the evolutionary consequences of the early stages of karyotypic differentiation (i.e. polymorphism), especially the non-meiotic impacts, is surprisingly limited. We review the available data on chromosomal polymorphisms in mammals so as to identify taxa that hold promise for developing a more comprehensive understanding of chromosomal change. In doing so, we address several key questions: (i) to what extent are mammalian karyotypes polymorphic, and what types of rearrangements are principally involved? (ii) Are some mammalian lineages more prone to chromosomal polymorphism than others? More specifically, do (karyotypically) polymorphic mammalian species belong to lineages that are also characterized by past, extensive karyotype repatterning? (iii) How long can chromosomal polymorphisms persist in mammals? We discuss the evolutionary implications of these questions and propose several research avenues that may shed light on the role of chromosome change in the diversification of mammalian populations and species

Extensive Amplification of Telomeric Repeats in the Karyotypically Highly Diverse African Pygmy Mice

International audienceTelomeres are ribonucleoprotein structures protecting the physical ends of eukaryotic chromosomes. However, telomeric sequences can also occur at non-terminal regions of chromosomes, forming the so-called interstitial telomeric sequences (ITSs). Some ITSs are considered as relics of past chromosomal rearrangements and as such provide important insights into karyotype evolution. By FISH, we explored the distribution of telomeric motifs in the genome of a complex of mammalian species that has long been recognized for its extraordinary karyotypic diversity: the African pygmy mice. This survey involved 5 species, representing 10 highly diverse karyotypes with or without autosomal and sex-autosome robertsonian (Rb) fusions. The study revealed that in species with an ancestral-like karyotype (i.e., no fusions; Mus mattheyi and M. indutus), only terminal telomeres were observed, whereas in species experiencing intense chromosomal evolution (e.g., M. minutoides, M. musculoides), a large amplification of telomeric repeats was also identified in the pericentromeric region of acrocentrics and most metacentrics. We concluded that (i) the mechanism of Rb fusion in the African pygmy mice is different than the one highlighted in the house mouse; (ii) the intensity of the ITS hybridization signal could be a signature of the age of formation of the Rb fusion; (iii) the large amplification of pericentromeric telomeric sequences in acrocentrics may mediate the formation of Rb fusions, and (iv) the ITSs on the sex-autosome fusion Rb(X.1) may participate to the insulation buffer between the sexual and autosomal arms to prevent X inactivation from spreading and silencing autosomal genes and allow the independent regulation of replication timing of both segments

Non-Random Occurrence of Robertsonian Translocations in the House Mouse <b><i>(Mus musculus domesticus)</i></b>: Is It Related to Quantitative Variation in the Minor Satellite?

International audienceThe house mouse, Mus musculus domesticus, shows extraordinary chromosomal diversity driven by fixation of Robertsonian (Rb) translocations. The high frequency of this rearrangement, which involves the centromeric regions, has been ascribed to the architecture of the satellite sequence (high quantity and homogeneity). This promotes centromere-related translocations through unequal recombination and gene conversion. A characteristic feature of Rb variation in this subspecies is the non-random contribution of different chromosomes to the translocation frequency, which, in turn, depends on the chromosome size. Here, the association between satellite quantity and Rb frequency was tested by PRINS of the minor satellite which is the sequence involved in the translocation breakpoints. Five chromosomes with different translocation frequencies were selected and analyzed among wild house mice from 8 European localities. Using a relative quantitative measurement per chromosome, the analysis detected a large variability in signal size most of which was observed between individuals and/or localities. The chromosomes differed significantly in the quantity of the minor satellite, but these differences were not correlated with their translocation frequency. However, the data uncovered a marginally significant correlation between the quantity of the minor satellite and chromosome size. The implications of these results on the evolution of the chromosomal architecture in the house mouse are discussed

With 2 figures

We assessed the fertility (reproductive success, litter size, testis weight, spermatocyte-to-spermatid ratio) of F 1 s and backcrosses between different wild-derived outbred and inbred strains of two mouse subspecies, Mus musculus domesticus and M. m. musculus . A significant proportion of the F 1 females between the outbred crosses did not reproduce, suggesting that female infertility was present. As the spermatocyte-to-spermatid ratio was correlated with testis weight, the latter was used to attribute a sterile vs. fertile phenotype to all males. Segregation proportions in the backcrosses of F 1 females yielded 11 (inbred) to 17% (outbred) sterile males, suggesting the contribution of two to three major genetic factors to hybrid male sterility. Only one direction of cross between the inbred strains produced sterile F 1 males, indicating that one factor was borne by the musculus X-chromosome. No such differences were observed between reciprocal crosses in the outbred strains. The involvement of the X chromosome in male sterility thus could not be assessed, but its contribution appears likely given the limited introgression of X-linked markers through the hybrid zone between the subspecies. However, we observed no sterile phenotypes in wild males from the hybrid zone, although testis weight tended to decrease in the centre of the transect