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

Abstract

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.

Repurposing of synaptonemal complex proteins for kinetochores in Kinetoplastida

“…However, CENP-A is absent in some eukaryotic lineages such as holocentric insects [5], early-diverging Fungi [6] and Kinetoplastida [7]. Furthermore, it is known that compositions of kinetochores can vary considerably among eukaryotes [8] and that these components are highly divergent at the sequence level [8][9][10]. The most extreme case known to date is found in Kinetoplastida, for which no apparent direct homologues of the canonical kinetochore proteins were detected [11].…”

The kinetochore protein NNF1 has a moonlighting role in the vegetative development of Arabidopsis thaliana

“…NNF1 is one of the several rapidly evolving kinetochore proteins under positive selection (Pontremoli et al, 2021). To provide a snapshot of the rapidly changing nature of Arabidopsis NNF1, we analyzed the percentage amino acid substitutions between NNF1 homologs within the Brassicaceae family, to which A. thaliana belongs, and also with evolutionarily divergent representative model monocots, alongside two other known rapidly evolving kinetochore proteins for comparison, namely, CENH3 (an inner kinetochore protein) and MIS12 (an outer kinetochore protein) of the MIS12 complex.…”

“…However, the kinetochore proteins from plants are less characterized, although the ultrastructural morphology and behavior of the plant kinetochore are known since the 1950s (Schrader, 1953). Like centromeric proteins, most kinetochore proteins are fast‐evolving (Pontremoli et al, 2021) and hence display less sequence homology between their respective orthologs despite their functional conservation. Hence, only a few kinetochore proteins from the CCAN and KMN groups that offer high sequence identity with their yeast or mammalian counterparts have been characterized in plants (Yu et al, 2000).…”

Molecular conflicts disrupting centromere assembly contribute to Xenopus hybrid inviability

“…Centromeric DNA sequences and centromere and kinetochore proteins have been shown to rapidly co-evolve, which is thought to counteract female meiotic drive and maintain faithful chromosome segregation (Malik and Henikoff, 2001; Malik et al, 2002; Kumon et al, 2021; Pontremoli et al, 2021; Hooff et al, 2017). Our study reveals very low conservation of core centromere DNA sequences across three Xenopus species, and differences in protein sequences of Xenopus CENP-A and its chaperone HJURP are also observed, indicating co-evolution.…”