Mouse telocentric sequences reveal a high rate of homogenization and possible role in Robertsonian translocation

Abstract

The telomere and centromere are two specialized structures of eukaryotic chromosomes that are essential for chromosome stability and segregation. These structures are usually characterized by large tracts of tandemly repeated DNA. In mouse, the two structures are often located in close proximity to form telocentric chromosomes. To date, no detailed sequence information is available across the mouse telocentric regions. The antagonistic mechanisms for the stable maintenance of the mouse telocentric karyotype and the occurrence of whole-arm Robertsonian translocations remain enigmatic. We have identified large-insert fosmid clones that span the telomere and centromere of several mouse chromosome ends. Sequence analysis shows that the distance between the telomeric T 2AG3 and centromeric minor satellite repeats range from 1.8 to 11 kb. The telocentric regions of different mouse chromosomes comprise a contiguous linear order of T2AG3 repeats, a highly conserved truncated long interspersed nucleotide element 1 repeat, and varying amounts of a recently discovered telocentric tandem repeat that shares considerable identity with, and is inverted relative to, the centromeric minor satellite DNA. The telocentric domain as a whole exhibits the same polarity and a high sequence identity of >99% between nonhomologous chromosomes. This organization reflects a mechanism of frequent recombinational exchange between nonhomologous chromosomes that should promote the stable evolutionary maintenance of a telocentric karyotype. It also provides a possible mechanism for occasional inverted mispairing and recombination between the oppositely oriented TLC and minor satellite repeats to result in Robertsonian translocations.centromere ͉ chromosome ͉ evolution ͉ telomere

Integrity of the human centromere DNA repeats is protected by CENP-A, CENP-C, and CENP-T

“…We found different types of centromere aberrations in U2OS ( Fig. 2A, i-iv), in line with evidence suggesting that satellite changes are driven by different mutational processes, from recombination to unequal exchange and translocation (18,28). The majority of rearrangements observed were as in Fig.…”

Localization of Telomeric Sequences in the Chromosomes of Three Species of Calomys (Rodentia, Sigmodontinae)

“…For instance, in M. musculus domesticus, the paradigmatic case of centric fusion, no telomeric sequences are retained in the biarmed chromosomes (Garagna et al 1995, Nanda et al 1995, Kalitsis et al 2006; no ITS are observed either in the biarmed chromosomes of the shrew Suncus murinus (Rogatcheva et al 2000). In other cases with a high level of Rb (Robertsonian) variation, such as in the Sorex araneus complex (Zhdanova et al 2005) and Mus minutoides (Castiglia et al 2002(Castiglia et al , 2006, the opposite situation is the rule.…”

Centromere Evolution: Digging into Mammalian Primary Constriction

“…The minor and major satellite sequences are highly conserved across the centromeres of all mouse telocentric chromosomes: the minor satellite monomers share a mean pairwise identity of 95% (Kalitsis et al, 2006); the major satellite monomers share a mean deviation from the consensus sequence of 3.9% (Vissel & Choo, 1989). This high degree of sequence conservation argues strongly for frequent recombinational exchanges between nonhomologous telocentric chromosomes driving sequence homogenization at mouse centromeres (Kalitsis et al, 2006;Vissel & Choo, 1989).…”

“…This high degree of sequence conservation argues strongly for frequent recombinational exchanges between nonhomologous telocentric chromosomes driving sequence homogenization at mouse centromeres (Kalitsis et al, 2006;Vissel & Choo, 1989).…”