Previous work found that the centromeric repeats of the Western European house mouse (Mus musculus domesticus) are composed predominantly of a 120 bp monomer that is shared by the X and autosomes. Polymorphism in length and sequence was also reported. Here I quantified the length and sequence polymorphism of the centromeric repeats found on the X and autosomes. The levels of local and global sequence variation were also compared. I found three length variants: a 64mer, 112mer and 120mer with relative frequencies of 2.4%, 8.6%, and 89%, respectively. There was substantial sequence variation within all three length variants with a rank-order of: 64mer < 120mer < 112mer. The 64mer was never found alone on long Sanger traces, and was arranged predominantly as a 176 bp higher-order repeat composed of a 64/112mer dimer. Reanalysis of archived ChIP-seq reads found that all three length variants were enriched with the foundational centromere protein CENP-A, but the enrichment was far higher for the 120mer. This pattern indicates that only the 120mer contributes substantially to the functional centromeres, i.e., to the kinetochore-binding, centric cores of the centromeric repeat arrays. Despite only moderate sequence divergence among random pairs of 120mers (averaging 5.9%), other measures of sequence diversity were exceptionally high: i) variant richness (numerical diversity) –on average, one new sequence variant was observed every 4th additional monomer randomly sampled (in N = 7.2 × 103 monomers), and ii) variant evenness –all of the nearly 2 × 103 observed sequence variants were at low frequency, with the most common variant having a frequency of only 5.7%. I next used long Sanger trace data from the Mouse Genome Project to assess the pattern of monomer diversity among neighboring 120mers. Unexpectedly, side-by-side monomers were rarely identical in sequence, and sequence divergence between these neighbors was nearly as high as that between random pairs taken from the genome-wide pool of all 120mers. I also used long Sanger traces to determine sequence variation among neighborhoods of 5 contiguous 120 bp monomers. Sequence diversity within these small regions typically spanned most of the entire range of that found genome-wide. Despite high sequence variation within these neighborhoods, the density of monomers with functional binding motifs for CENP-B (i.e., b-boxes with sequence NTTCGNNNNANNCGGGN) was strongly conserved at about 50%. The overarching pattern of monomer structure at the centromeric repeats of this subspecies is: i) high homogeneity in the density CENP-B binding sites, and ii) high heterogeneity in monomer sequence at both local and global levels.
Weak Correlation between Nucleotide Variation and Recombination Rate across the House Mouse Genome
