Centromere drive and suppression by parallel pathways for recruiting microtubule destabilizers

Abstract

SummarySelfish centromere DNA sequences bias their transmission to the egg in female meiosis. Evolutionary theory suggests that centromere proteins evolve to suppress costs of this “centromere drive”. In hybrid mouse models with genetically different maternal and paternal centromeres, selfish centromere DNA exploits a kinetochore pathway to recruit microtubule-destabilizing proteins that act as drive effectors. We show that such functional differences are suppressed by a parallel pathway for effector recruitment by heterochromatin, which is similar between centromeres in this system. Disrupting heterochromatin by CENP-B deletion amplifies functional differences between centromeres, whereas disrupting the kinetochore pathway with a divergent allele of CENP-C reduces the differences. Molecular evolution analyses using newly sequenced Murinae genomes identify adaptive evolution in proteins in both pathways. We propose that centromere proteins have recurrently evolved to minimize the kinetochore pathway, which is exploited by selfish DNA, relative to the heterochromatin pathway that equalizes centromeres, while maintaining essential functions.

Cross-species incompatibility between a DNA satellite and the Drosophila Spartan homolog poisons germline genome integrity

“…Evidence for this coevolution model has emerged from engineering "evolutionary mismatches" between the chromatin protein(s) of one species and the DNA satellite landscape of a close relative. Under one approach, a diverged chromatin protein is introduced into a closely related species, generating an evolutionary mismatch between the manipulated protein and one or more DNA satellites [14][15][16][17]. Consistent with disrupted DNA satellite:chromatin protein coevolution, the naïve chromatin protein typically perturbs a satellite-mediated function, such as chromosome segregation or nuclear organization [14,16,17].…”

“…Under one approach, a diverged chromatin protein is introduced into a closely related species, generating an evolutionary mismatch between the manipulated protein and one or more DNA satellites [14][15][16][17]. Consistent with disrupted DNA satellite:chromatin protein coevolution, the naïve chromatin protein typically perturbs a satellite-mediated function, such as chromosome segregation or nuclear organization [14,16,17]. In these cases, however, the incompatible DNA satellites are unknown.…”

Unravelling the mystery of female meiotic drive: where we are

“…The kinetochore pathway (discussed above) functions through kinetochore recruitment of BUB1 [38,53,54]. Independently, the CPC can localize to pericentromeric heterochromatin and recruit SGO2 and MCAK in the heterochromatin pathway [58][59][60][61]. Kumon et al suggest that evolutionary shifts which lead to less reliance on the kinetochore pathway and more reliance on the heterochromatin pathway is a route for genome suppression of centromere drive [58].…”

“…Independently, the CPC can localize to pericentromeric heterochromatin and recruit SGO2 and MCAK in the heterochromatin pathway [58][59][60][61]. Kumon et al suggest that evolutionary shifts which lead to less reliance on the kinetochore pathway and more reliance on the heterochromatin pathway is a route for genome suppression of centromere drive [58]. Conversely, it is possible that centromeric and pericentromeric DNA function selfishly as one unit and manipulate their pericentromere to recruit more destabilizing factors.…”

Putting the brakes on centromere drive in Mimulus

“…guttatus might have been selected to disfavor binding to D , thereby suppressing centromere drive. Indeed, centromere-binding proteins with low centromeric affinity can weaken meiotic drive in mice [ 13 ]. The relative affinity of Mimulus CenH3A proteins for satellites between competing centromeres could explain why this new study found no straightforward hierarchy in CenH3A allele combinations and drive suppression in the new study.…”