Rapid evolution of mouse Y centromere repeat DNA belies recent sequence stability

Abstract

The Y centromere sequence of house mouse, Mus musculus, remains unknown despite our otherwise significant knowledge of the genome sequence of this important mammalian model organism. Here, we report the complete molecular characterization of the C57BL/6J chromosome Y centromere, which comprises a highly diverged minor satellite-like sequence (designated Ymin) with higher-order repeat (HOR) sequence organization previously undescribed at mouse centromeres. The Ymin array is ;90 kb in length and resides within a single BAC clone that provides sequence information spanning an endogenous animal centromere for the first time. By exploiting direct patrilineal inheritance of the Y chromosome, we demonstrate stability of the Y centromere DNA structure spanning at least 175 inbred generations to beyond the time of domestication of the East Asian M.m. molossinus ''fancy'' mouse through which the Y chromosome was first introduced into the classical inbred laboratory mouse strains. Despite this stability, at least three unequal genetic exchange events have altered Ymin HOR unit length and sequence structure since divergence of the ancestral Mus musculus subspecies around 900,000 yr ago, with major turnover of the HOR arrays driving rapid divergence of sequence and higher-order structure at the mouse Y centromere. A comparative sequence analysis between the human and chimpanzee centromeres indicates a similar rapid divergence of the primate Y centromere. Our data point to a unique DNA sequence and organizational architecture for the mouse Y centromere that has evolved independently of all other mouse centromeres.

Sequences Associated with Centromere Competency in the Human Genome

“…While the vast majority of enriched sites are associated with higher-order repeat arrays in the genome, we were also able to track low-frequency CENP-A enrichment in nonhomogenized monomeric subsets in pericentromeric regions adjacent to the centromere gaps in the current assembly, in agreement with a previously reported observation of divergent satellite adjacent to the centromere on the mouse Y chromosome (40). For example, we found evidence of CENP-A enrichment extending 12.6 kb from the DXZ1 array over adjacent monomeric monomers in the p-arm assembly, in agreement with previous studies that described the CENP-A domain closer to the p-arm of the array (7,41) (Fig.…”

Radical remodeling of the Y chromosome in a recent radiation of malaria mosquitoes

“…On the Y chromosome such regions may be subject to accelerated rates of divergence compared with the rest of the genome. Between humans and chimps whose lineages diverged ∼5 Mya, orthologous satellite arrays in the X centromere are collinear and share 93% sequence identity, whereas collinearity declines and sequence conservation drops to 78% between orthologous satellites in Y centromeres (65). Additional evidence of rapid length, structure, and sequence evolution of satellites and ampliconic structures on the Y chromosome has been reported in mice species 1-2 My diverged and mice subspecies separated by only ∼900,000 y (65), between D. melanogaster and D. simulans that split ∼4 Mya (60,66), and among human males worldwide (67).…”

Contrasting roles of condensin I and II in mitotic chromosome formation

“…Wild-type DT40 cells were treated with colcemid for two hours before being fixed in ice-cold methanol acetic acid and dropped onto glass slides. Chromosome spreads were dried, and fluorescence in situ hybridization (FISH) was performed, as described previously (Pertile et al, 2009). …”