Resumen de On the role of chromosomal rearrangements in evolution: Recosntruction of genome resuffling in rodents and analysis of robertsonian fusions in a house mouse chromosomal polymorphism zone
In order to understand the evolutionary dynamics of mammalian genomes, is necessary to analyze chromosome configuration as well as the genomic changes that have occurred at a large-scale (in the form of chromosomal rearrangements) and at a micro-scale (in the form of nucleotide changes) within species. Chromosomal rearrangements (i.e., inversions, translocations, fusions or fissions) have played a crucial role during evolution as they have led to genomic changes with consequences for the species differentiation. Within mammals, rodents represent the most specious taxon with a wide spectrum of karyotypes.
In this thesis, we have first analyzed the chromosomal reorganizations along rodents evolution together with the factors that have been involved in the distribution of chromosomal rearrangements. Taking advantage of the increasing number of available whole-genomes sequenced, we have compared the genomes of six rodent species (including the mouse genome as a reference) and six outgroup species corresponding to different mammalian taxa (Primates, Artiodactyla, Carnivora and Perissodactyla). We have identified genomic regions of homology (or homologous synteny blocks, HSBs) and the regions of synteny disruption (or Evolutionary Breakpoint regions, EBRs) among rodents. Moreover, the localization of EBRs has permitted us to analyze the genomic features that could be involved in the origin of chromosomal rearrangements. Our results showed that EBRs present a non-homogeneus distribution across the mouse genome. Additionally, EBRs are characterized by specific genomic features such as higher gene content, lower recombination rates and low proportion of lamina associated domains (cLADs) compared with the rest of the mouse genome.
Secondly, it is known that the western house mouse (Mus musculus domesticus) natural populations present a wide variety of diploid numbers due to the presence of Robertsonian (Rb) fusions. Within all these populations analyzed, one of them, localized in the Barcelona, Lleida and Girona provinces, presents a specific structure, where no metacentric race has been described, being the Rb fusions found in a polymorphic state. This chromosomal polymorphism zone is known as The Barcelona Rb system. Giving the specific characteristics of this population, we have: (i) analyzed the role of telomeres in the occurrence of the Rb fusions and (ii) studied the effect of the Rb fusions and Prdm9 gene on meiotic recombination. We have detected that telomere shortening in acrocentric p-arms can be one of the factors that could explain the occurrence of Rb fusions by promoting the interaction between chromosomal ends and thus, to the fusion events. Moreover, we have observed that the presence of Rb fusions leads to a decrease in recombination rates due to a re-distribution of crossovers towards the telomeres in metacentric chromosomes. Furthermore, we have detected that this phenomenon is due to an interference effect of the centromere in metacentric chromosomes, which acts suppressing recombination within the pericentromeric regions. Additionally, we have also characterized the Prdm9 allelic distribution within the Barcelona Rb polymorphism system, as well as an effect of the Prdm9 sequence on recombination rates.
Therefore, and in the light of our results, we propose that the effect of suppression of recombination on individuals with Rb fusions is due to a mechanicstic (by the centromeric interference effect) and genetic (the Prdm9 allelic sequence) factors. These results, together with the characterization of the genomic features that have been involved in the occurrence of evolutionary chromosomal rearrangements in rodents, would help us to understand the dynamics of chromosomal speciation along evolution and how chromosomal rearrangements occur in natural populations.
