Evolution and molecular dynamics of centromeres in the genus Equus

The centromere is the locus directing chromosome segregation at cell division. The mechanism by which centromere identity is specified on chromosomal DNA sequences has been deeply enigmatic, with a clear dependence on the epigenetic inheritance of the centromeric histone, CENP-A. While a degree of autonomy of centromere placement along the chromosome has been established by studies of human neocentromeres and observation of evolutionary centromere repositioning, a role for DNA sequence in driving centromere location remains to be elucidated. The typical association of mammalian centromeres with extensive arrays of highly repetitive satellite DNA, has so far hampered a detailed molecular dissection of centromere function and evolution. In previous work, we discovered that, in the genus Equus (horses, asses and zebras), centromere repositioning during evolution was exceptionally frequent and that satellite DNA and centromeres are often uncoupled in this genus (Piras et al, PLoS Genet 2010, 6 e1000845). We then described the first native satellite-free centromere discovered in a mammal, that of horse chromosome 11 (Wade et al, Science 2009, 326: 865-867); using a combination of molecular and cytogenetic approaches we recently demonstrated that the precise positioning of this native mammalian centromere is highly variable, even on the two homologous chromosomes in a single individual. These results corroborate the hypothesis that CENP-A is the principal determinant of centromere identity, but they make a much deeper point: CENP-A location along the DNA polymer is not fixed but rather exhibits a diffusion-like behavior. We are now characterizing a number of satellite-less centromeres in asses and zebras; preliminary observations on the molecular organization of centromeres, based on the exploitation of this powerful model system, will be presented