Kinetochore proteins and microtubule-destabilizing factors are fast evolving in eutherian mammals

Centromeres have central functions in chromosome segregation, but centromeric DNA and centromere-binding proteins evolve rapidly in most eukaryotes. The selective pressure(s) underlying the fast evolution of centromere-binding proteins are presently unknown. An attractive possibility is that selfish centromeres promote their preferential inclusion in the oocyte and centromeric proteins evolve to suppress meiotic drive (centromere drive hypothesis). We analysed the selective patterns of mammalian genes that encode kinetochore proteins and microtubule (MT)-destabilizing factors. We show that several of these proteins evolve at the same rate or faster than proteins with a role in centromere specification. Elements of the kinetochore that bind MTs or that bridge the interaction between MTs and the centromere represented the major targets of positive selection. These data are in line with the possibility that the genetic conflict fuelled by meiotic drive extends beyond genes involved in centromere specification. However, we cannot exclude that different selective pressures underlie the rapid evolution of MT-destabilizing factors and kinetochore components. Whatever the nature of such pressures, they must have been constant during the evolution of eutherian mammals, as we found a surprisingly good correlation in dN/dS (ratio of the rate of nonsynonymous and synonymous substitutions) across orders/clades. Finally, when phylogenetic relationships were accounted for, we found little evidence that the evolutionary rates of these genes change with testes size, a proxy for sperm competition. Our data indicate that, in analogy to centromeric proteins, kinetochore components are fast evolving in mammals. This observation may imply that centromere drive plays out at multiple levels or that these proteins adapt to lineage-specific centromeric features.

Automated summary

The study found that genes encoding kinetochore proteins and microtubule-destabilizing factors in mammals evolve rapidly, suggesting a genetic conflict fueled by meiotic drive beyond centromere-specific genes. The rapid evolution of these proteins may imply a role in centromere drive at multiple levels or adaptation to lineage-specific centromeric features.