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

Abstract

BackgroundRecent 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 Mus which exhibits a high rate of karyotypic change, a large fraction of which involves centromeres.ResultsThe chromosomal distribution of rDNA clusters was determined by in situ 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 Mus: 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.ConclusionsThis study on the dynamics of rDNA clusters within the genus Mus has revealed a strong evolutionary relationship between rDNA clusters and centromeres. Both of these genomic structures coincide with breakpoints in the genus Mus, 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.

Chromosomal dynamics of nucleolar organizer regions (NORs) in the house mouse: micro-evolutionary insights

“…The existence of minor NOR-bearing chromosomes that are common to several subspecies (NORs 4,6,8,9,10,17) suggests that they either correspond to low frequency ancestral polymorphisms or, if they originated by de novo transposition, this event occurred sufficiently early during the differentiation process for them to spread to the different sublineages. That a large number of ancestral NORs may be present in this species is supported by the high number of NORs recorded in the subgenus Mus (Cazaux et al, 2011). In fact, in each of the three main clades of the subgenus, one to several species carry NORs on all (19) or almost all (16) autosome pairs.…”

“…If rare or unique sites are the only ones to have been generated by de novo transposition, this would imply an inter-chromosomal transposition rate of six events in 0.5 MY at the most (Geraldes et al, 2008;Duvaux et al, in press). located except in one species, Mus spretus, in which three telomeric NORs have been described (4T, 13T, 19T;Winking et al, 1980;Cazaux et al, 2011). The coincidence in location in the two taxa is intriguing.…”

“…The following nomenclatures were adopted: NOR followed by a number designates the NOR-bearing chromosome; telomeric NORs are indicated by a T after the chromosome number; a NOR site refers to the location of the rRNA genes on a single chromosome. The data were completed with those available in the literature for wild individuals of DOM, MUS, CAS and MOL, using either the FISH approach (Fel-Clair et al, 1998;Ito et al, 2007Ito et al, , 2008Cazaux et al, 2011), or the Ag-NOR staining method when genotype scores could be extracted (Winking et al, 1980;Suzuki et al, 1990;Ramalhinho et al, 2005). Details on the procedure used for genotype scoring are indicated in Supplementary Table S1.…”

“…A previous phylogenetic analysis of NOR variation within the subgenus indicated that the number and location of clusters between species differed, each taxon showing its own chromosomal distribution (Cazaux et al, 2011). This extensive NOR diversity indicated that high rates of inter-chromosomal transposition existed within the Mus genome in the absence of cytogenetically visible rearrangements.…”

“…As the number and position of the rDNA clusters are often species-specific, these chromosomal characters have been widely used in systematics and phylogenetic reconstructions. Studies on NOR variation in numerous plant, insect and vertebrate groups have invariably described changes in the number and chromosomal location of NORs even in closely related species, suggesting that rDNA clusters are highly mobile components of the genome (Gallagher et al, 1999;Datson and Murray, 2006;Cabrero and Camacho, 2008;Nguyen et al, 2010;da Silva et al, 2010;Cazaux et al, 2011). This important inter-species lability is generated either by chromosomal rearrangements or transposition events (Eickbush and Eickbush, 2007).…”