A selfish supergene causes meiotic drive through both sexes in Drosophila

Abstract

Meiotic drivers are selfish genetic elements that bias their own transmission during meiosis or gamete formation. Due to the fundamental differences between male and female meiosis in animals and plants, meiotic drivers operate through distinct mechanisms in the two sexes: In females, they exploit the asymmetry of meiosis to ensure their inclusion in the egg, whereas in males, they eliminate competing gametes after symmetric meiosis. Meiotic drive is commonly reported in males, where it strongly influences the evolution of spermatogenesis, while the few known cases in females have highlighted its crucial role in centromere evolution. Despite a growing number of examples in a wide range of organisms, meiotic drive has so far only been observed in one sex or the other since its discovery nearly 100 y ago. Here, we show that a selfish X chromosome known to cause meiotic drive in male Drosophila testacea flies also causes meiotic drive in females. We find that this X chromosome has supergene architecture, harboring extensive structural rearrangements that suppress recombination between the two X chromosomes. This has contributed to a substantial expansion of its size compared to the wild-type chromosome, partly due to the accumulation of species-specific repetitive elements. Our findings suggest that female meiotic drive may play an important role in the evolutionary dynamics of polymorphic structural variants that suppress recombination, including inversions, translocations, and supergenes.

Keywords: meiotic drive; selfish genetic elements; sex chromosome; supergenes.

Fig. 1.

Non-Mendelian transmission of driving X chromosomes through females. (A) Females heterozygous for driving and bright-eye X chromosomes (X^DX^b; n = 64) crossed with bright-eyed males (X^bY) produce significantly more WT-eyed offspring than the Mendelian expectation of 50% (mean proportion WT-eyed = 0.63, 95% CI 0.61-0.65, one sample t test: P < 0.001), revealing biased transmission of the driving X chromosome. Females heterozygous for wild type and bright-eye X chromosomes (XX^b; n = 22) do not produce significantly different numbers of WT- and bright-eyed offspring (mean proportion WT-eyed = 0.50, 95% CI 0.48-0.51, one sample t test: P > 0.05). Purple bars indicate the means; the dashed line indicates the Mendelian expectation of 50%. (B) Pooled counts of offspring genotypes from all X^DX^b females shown in (A) and (C) from all XX^b females shown in (A).

Fig. 2.

Distortion of the driving X chromosome occurs prezygotically. (A) Of 214 embryos from three X^DX^b females, 138 embryos inherited the X^D (proportion X^D = 0.65, 95% CI = 0.58-0.71, binomial test: P < 0.001). All three females transmitted the X^D more than the X^b, with females fe1, DB13, and fe6 transmitting the X^D to 72% (n = 93), 58.7% (n = 63), and 58.6% (n = 58) of embryos, respectively. (B) Pooled counts of offspring genotypes from the three X^DX^b females in (A). (C) Female genotype (XX or X^DX) does not significantly affect egg hatch rate (logistic regression: P > 0.05), demonstrating that the distortion observed in adults is not explained by differential survival of embryos. (D) The fecundity of XX and X^DX females are not significantly different (Tukey post hoc test: P > 0.05), while X^DX^D suffer reduced fecundity (Tukey post hoc test: X^DX^D vs. X^DX^b, P < 0.05; X^DX^D vs. X^bX^b, P > 0.05). Purple bars indicate the means.

Fig. 3.

X chromosome heteromorphism and structural variation in the D. testacea driving X chromosome system. The wild type D. testacea X chromosome (white arrows) is acrocentric, with a short heterochromatic arm, as seen in mitotic chromosome spreads from larval neuroblasts of (A) X^bX^b females and (B) X^bY males (the cyan arrow indicates the Y chromosome). (C) In contrast, the heterochromatic arm of the driving X chromosome (red arrow) is massively expanded, as seen clearly in X^DX^b females. (Scale bar, 10 μm.) (D) Alignments of X-linked contigs from the XY (Top) and X^DY (Bottom) genome assemblies reveal extensive chromosomal rearrangements (contigs are arranged by size). Gene trees of genes along the X chromosome show blocks of genes with discordant topologies. The vertical bars along each contig show orthologues between the D. testacea and D. neotestacea X chromosomes (with D. putrida as the outgroup), colored by their gene tree topology. Orthologues between the X and X^D are connected with lines. (E) Discordant genes have elevated Ks between the X and X^D copies. (F) Read coverage of XY and X^DY nanopore reads mapped to contig_1802 in the X^DY genome reveals a region unique to the driving X chromosome. (G) Dot plot showing a satellite repeat block at the 5’ end of contig_1802 (H) qPCR copy number analysis shows that the satellite is repeated ∼75 to 100 times on different driving X chromosome lines (purple bars indicate the means).

Fig. 4.

The origin and evolutionary dynamics of meiotic drive through both sexes. The fate of a driving X chromosome that causes meiotic drive in (A) males only and (B) both sexes. For both scenarios, the driving X chromosome was introduced at low frequency and simulations were run for 10,000 generations for each combination of X^DY and X^DX^D fitnesses. The heatmap colors show the frequency of the driving X chromosome at the end of each simulation. The solid black lines indicate analytically derived conditions from the model m and n are the male and female drive strength parameters, respectively. See SI Appendix for model and simulation details. (C) The proportion of the two-dimensional parameter space in each of A and B leading to the three possible outcomes of fixation, polymorphism, and failure to invade. (D) Under certain fitness combinations (shaded area), a male driving X chromosome can evolve female drive without spreading to fixation, allowing for the stepwise evolution of drive in both sexes ending in polymorphism. Solid lines are the analytically derived conditions shown in A and B. The dotted line indicates an estimate of the contemporary fitness of X^DX^D (SI Appendix). (E) A schematic for the stepwise evolution of meiotic drive in both sexes. The X chromosome evolves to drive in males first and is prevented from spreading to fixation via male fertility costs and/or suppression. The driving X chromosome then evolves suppressed recombination and diverges from the wild type X chromosome over time. Such divergence is exploited for female drive, leading to a new polymorphism with drive through both sexes.