Adaptive Evolution of Foundation Kinetochore Proteins in Primates

Rapid evolution is a hallmark of centromeric DNA in eukaryotic genomes. Yet, the centromere itself has a conserved functional role that is mediated by the kinetochore protein complex. To broaden our understanding about both the DNA and proteins that interact at the functional centromere, we sought to gain a detailed view of the evolutionary events that have shaped the primate kinetochore. Specifically, we performed comparative mapping and sequencing of the genomic regions encompassing the genes encoding three foundation kinetochore proteins: Centromere Proteins A, B, and C (CENP-A, CENP-B, and CENP-C). A histone H3 variant, CENP-A provides the foundation of the centromere-specific nucleosome. Comparative sequence analyses of the CENP-A gene in 14 primate species revealed encoded amino-acid residues within both the histone-fold domain and the N-terminal tail that are under strong positive selection. Similar comparative analyses of CENP-C, another foundation protein essential for centromere function, identified amino-acid residues throughout the protein under positive selection in the primate lineage, including several in the centromere localization and DNA-binding regions. Perhaps surprisingly, the gene encoding CENP-B, a kinetochore protein that binds specifically to alpha-satellite DNA, was not found to be associated with signatures of positive selection. These findings point to important and distinct evolutionary forces operating on the DNA and proteins of the primate centromere.