Molecular Evolution at a Meiosis Gene Mediates Species Differences in the Rate and Patterning of Recombination

Abstract

Crossing over between homologous chromosomes during meiosis repairs programmed DNA double-strand breaks, ensures proper segregation at meiosis I [1], shapes the genomic distribution of nucleotide variability in populations, and enhances the efficacy of natural selection among genetically linked sites [2]. Between closely related Drosophila species, large differences exist in the rate and chromosomal distribution of crossing over. Little, however, is known about the molecular genetic changes or population genetic forces that mediate evolved differences in recombination between species [3, 4]. Here, we show that a meiosis gene with a history of rapid evolution acts as a trans-acting modifier of species differences in crossing over. In transgenic flies, the dicistronic gene, mei-217/mei-218, recapitulates a large part of the species differences in the rate and chromosomal distribution of crossing over. These phenotypic differences appear to result from changes in protein sequence not gene expression. Our population genetics analyses show that the protein-coding sequence of mei-218, but not mei-217, has a history of recurrent positive natural selection. By modulating the intensity of centromeric and telomeric suppression of crossing over, evolution at mei-217/-218 has incidentally shaped gross differences in the chromosomal distribution of nucleotide variability between species. We speculate that recurrent bouts of adaptive evolution at mei-217/-218 might reflect a history of coevolution with selfish genetic elements.

Keywords: Drosophila; centromere effect; crossing over; evolution; genetic hitchhiking; interference; positive selection; recombination.

Figure 1. The mei-217/mei-218 gene region and genotypes assayed for crossing over

(A) Within the ~8.5-kb region cloned (gray) the mei-217/-218 gene (light blue) on chromosome X (15E5) gives rise to a single dicistronic transcript (green) that encodes both the MEI217 and MEI218 proteins from different exons and different translation initiation sites (purple; ref. [20]). (B) Three genotypes were used to test if the D. mauritiana and D. melanogaster alleles of mei-217/-218 mediate species differences in rates of crossing over: females with no transgene (a negative control); females with a transgene of a D. melanogaster mei-217/-218 allele (a positive control); and females with a transgene of a D. mauritiana mei-217/-218 allele. The two transgenes were inserted into the same position on chromosome 3L (75A10). The endogenous mei-218¹ allele contains a nonsense mutation [14]. Crossover frequencies were scored among six visible markers spanning the left arm of chromosome 2 and the centromere: net (net), decapentaplegic (ho), dumpy (dp), black (b), purple (pr), cinnabar (cn). For additional details on genotype construction, see STAR Methods and Figure S2.

Figure 2. The distribution of positively selected codons in mei-217 and mei-218 in D. melanogaster and D. mauritiana

(A) The N-terminal basic and central acidic regions of MEI-218 are encoded by codons 1–500 and 500–800, respectively, and the MCM domain is encoded by codons 1019–1124 (ref. [35]). Nearly all of the positively selected codons fall within the first 800 codons of mei-218, and none occur in the MCM domain. In mei-217, a single codon in D. melanogaster has a 0.52 probability of positive selection, whereas no codons in D. mauritiana mei-217 have a ≥0.50 probability of positive selection. Codon substitutions are indicated as red (nonsynonymous) and blue (synonymous) circles. (B) The standardized density of single nucleotide polymorphisms (SNPs) per site in 50-kb windows across chromosome 2 plotted for D. melanogaster (blue) and D. mauritiana (red) with loess-smoothed curves. For each chromosome arm (2L and 2R) and species, SNP densities were standardized by the respective maximum value. Gray triangles show the positions of the six visible markers used to score crossover frequencies. See STAR methods for more details.