Putting the brakes on centromere drive in Mimulus

Abstract

Asymmetric female meiosis in plants and animals is a battleground. Homologous chromosomes compete with each other for transmission through meiosis based on their centromeric DNA that recruits the chromosome segregation apparatus. Larger centromeres may recruit more centromeric proteins (centromere strength) and segregate into eggs more often than expected by mendelian inheritance ("centromere drive") [1]. This subversion of female meiosis by "selfish centromeres" can be harmful and lower host fitness. Therefore, suppressors of centromere drive are predicted to arise, especially in centromeric proteins like CenH3/CENP-A. There is ample support for the first step of centromere drive [2][3][4], with one of the best demonstrations coming from studies in Mimulus monkeyflowers, in which a centromeric variant locus (D) undergoes centromere drive in interspecies and intraspecies crosses [2,5]. However, evidence of the second step of the model, i.e., suppression of centromere drive by centromeric proteins, remains elusive. A new study by Finseth and colleagues [6] dates the evolutionary origin of the D centromere to within the past 1,500 years of Mimulus guttatus evolution. It also reveals genetic variation in susceptibility to drive within M. guttatus, including a modifier of drive that maps to a CenH3 paralog, which adaptively evolved after the driving D centromere.A previous study had associated expanded centromere-specific repeats within D with its drive ability [2]. In the new study, Finseth and colleagues showed that half of Chromosome 11 (>12 Mb) is genetically linked to the selfish centromere on D (MDL11). Only 9 unique SNPs have accumulated in approximately 256,000 nucleotides of coding sequences across 13 distinct D lines. Based on this high similarity, the authors conclude that D arose within the last 1,000 to 1,500 years in M. guttatus after experiencing a recent selective sweep. In addition to an expanded array of repetitive satellite DNA, the MDL11 locus spans >387 protein-coding genes, including 45 genes unique to D chromosomes. It is likely that both centromeric repeats and linked genes contribute to drive (Fig 1).M. guttatus D drives strongly against its counterpart centromere (d) from the self-fertilizing sister species Mimulus nasutus (D:d = >98:2 [7]), and it drives weakly against intraspecies D − (D:D − = 58:42 [2]). A trade-off between its drive ability and its cost to fertility maintains D at a frequency of 30% to 45% in M. guttatus populations [2,5]. Finseth and colleagues explored whether other genetic loci could influence the strength of D drive. Genetic loci linked to the drive locus should accumulate enhancers of drive, whereas unlinked genomic loci should accumulate suppressors of drive to restore genome fitness [8][9][10].To identify modifiers of drive, Finseth and colleagues adopted an ingenious genetic mapping strategy. They tested drive of M. guttatus D against M. nasutus d or M. guttatus D − in distinct genetic backgrounds comprised of different genomic combinations of both species. Consi...