Selfish chromosomal drive shapes recent centromeric histone evolution in monkeyflowers

Abstract

Centromeres are essential mediators of chromosomal segregation, but both centromeric DNA sequences and associated kinetochore proteins are paradoxically diverse across species. The selfish centromere model explains rapid evolution by both components via an arms-race scenario: centromeric DNA variants drive by distorting chromosomal transmission in female meiosis and attendant fitness costs select on interacting proteins to restore Mendelian inheritance. Although it is clear than centromeres can drive and that drive often carries costs, female meiotic drive has not been directly linked to selection on kinetochore proteins in any natural system. Here, we test the selfish model of centromere evolution in a yellow monkeyflower (Mimulus guttatus) population polymorphic for a costly driving centromere (D). We show that the D haplotype is structurally and genetically distinct and swept to a high stable frequency within the past 1500 years. We use quantitative genetic mapping to demonstrate that context-dependence in the strength of drive (from near-100% D transmission in interspecific hybrids to near-Mendelian in within-population crosses) primarily reflects variable vulnerability of the non-driving competitor chromosomes, but also map an unlinked modifier of drive coincident with kinetochore protein Centromere-specific Histone 3 A (CenH3A). Finally, CenH3A exhibits a recent (<1000 years) selective sweep in our focal population, implicating local interactions with D in ongoing adaptive evolution of this kinetochore protein. Together, our results demonstrate an active co-evolutionary arms race between DNA and protein components of the meiotic machinery in Mimulus, with important consequences for individual fitness and molecular divergence.

Fig 1. The Mimulus guttatus centromeric driver (D) is an extended low-recombination haplotype with distinct sequence content.

Top panel: Suppressed recombination between driving D and non-driving D^- haplotypes causes elevated linkage disequilibrium (r²) across Meiotic Drive Locus 11 (MDL11) in the Iron Mountain (IM) population of M. guttatus (heatmap of r² plotted by megabase position on x- and y-axes; N = 34 inbred lines). Lower panels, from top to bottom: the chromosome-wide density of putatively centromeric Cent728 repeats in the D reference genome; nucleotide diversity (π) per gene for D (n = 14) and D^- lines (n = 20); divergence (d_x,y.) per gene between D and D^- lines; and the ratio of exon coverage in D^- lines vs. D lines when aligned to the D reference genome (values near zero suggest deletion in D^- vs. D haplotype, whereas values near 2 suggest duplication).

Fig 2. Crossing design for mapping unlinked modifiers of heterospecific (Dd) and conspecific (DD^-) drive.

Two pairs of chromosomes are shown: Chromosome 11 with the centromeric MDL11 locus outlined in black and a second pair representing the rest of the genome. D (IM160; dark blue and green) and D^- (IM767; pale blue) lines of M. guttatus were crossed to M. nasutus (grey) to generate heterospecific F₁ hybrids. Intercrossing the F₁s produced an F₂ mapping population segregating only DD^- and Dd at MDL11 due to strong heterospecific drive through the female Dd parent: green arrows) and in Mendelian ratios elsewhere (blue and grey arrows). F₂s were genotyped genome-wide (scored as NN, NG, GG) and at a marker that could distinguish the alternative CenH3A alleles donated by the IM160 and IM767 parents (G₁₆₀ and G_767, respectively).

Fig 3. The strength of conspecific vs. heterospecific drive depends on MDL11 genotype, as well as unlinked modifiers.

(A) A quantitative trait locus (QTL) scan of transmission ratio distortion in F₃ progeny of F₂ hybrids reveals unlinked modifier QTLs on Chromosome 9 and 14, in addition to the primary effect of MDL11 genotype. LOD score trace is smoothed, with a window size of four markers. B Genotype at CenH3A, which is centered under the Chromosome 14 modifier QTL, significantly influences D transmission in hybrids. Means ± 1 SE are shown for the eight F₂ genotypic classes: DD^- and Dd at MDL11and GG (IM160/IM767 M. guttatus), NG₁₆₀ (heterozygote with M. guttatus allele from IM160 parent), NG₇₆₇ (heterozygote with M. guttatus allele from IM767 parent), and NN (M. nasutus) at CenH3A. Total n = 146.

Fig 4. CenH3A exhibits a recent selective sweep, consistent with evolution in response to costly D spread.

Exonic single nucleotide polymorphisms (SNPs) across a 496 kilobase (kb) region flanking CenH3A (13.5–14 Mb on Chromosome 14) are displayed for each of 34 lines from the Iron Mountain population of M. guttatus. The ~2000 SNPs are ordered by genomic position, but the x-axis is not scaled to physical or genetic distance. SNPs are coded according to whether they match (purple) or differ from (green) the haplotype of IM1054, which bears one of the most common CenH3A-flanking haplotypes. The arrowhead and horizontal line mark the location of CenH3A. The seven haplotypes (1–7) were assigned manually and are outlined in black boxes. For visual resolution around CenH3A, the longest haplotype (> 620kb) was truncated. Haplotype details are given in S6 Table.

Fig 5. Hypothesized processes underlying differences between heterospecific (strong) and conspecific (weak) centromeric drive in yellow monkeyflowers, as well as population genetic signatures of recent D-CenH3A co-evolution in Iron Mountain (IM) Mimulus guttatus.

Shades of blue represent M. guttatus standing diversity at centromeres (ovals on chromosomes), CenH3A (pie shapes), and other loci, green represents the driving D centromere (potentially facilitated by linked genes), and grey represents the relatively drive-permissive centromere and genetic background of selfer M. nasutus.