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.

Molecular evolution of the meiotic recombination pathway in mammals

“…Our results highlight an evolutionary contrast between mammals and Drosophila. MCMDC2, the mammalian homolog of the mei-217/mei-218 gene that evolves rapidly and adaptively in Drosophila (Brand et al 2018), exhibits below-average rates of evolution compared to other recombination genes and shows no evidence of positive selection. These two homologs occupy different positions in the recombination pathway.…”

“…mei‐217/mei‐218 was targeted for functional analysis based on its profile of rapid evolution between D. melanogaster and D. mauritiana (Brand et al. ). PRDM9 , a protein that positions recombination hot spots in house mice and humans through histone methylation (Myers et al.…”

“…In contrast, we know very little about the genetics of recombination rate evolution between species. Divergence at the dicistronic gene mei-217/mei-218 explains much of the disparity in genetic map length between D. melanogaster and D. mauritiana (Brand et al 2018). mei-217/mei-218 is the only gene known to confer a recombination rate difference between species, although quantitative trait loci that contribute to shifts in rate among subspecies of house mice have been identified (Murdoch et al 2010;Balcova et al 2016).…”

“…With this approach, the role of natural selection in the evolution of the pathway can be evaluated. mei-217/mei-218 was targeted for functional analysis based on its profile of rapid evolution between D. melanogaster and D. mauritiana (Brand et al 2018). PRDM9, a protein that positions recombination hot spots in house mice and humans through histone methylation (Myers et al 2010;Parvanov et al 2010;Grey et al 2011;Paigen and Petkov 2018), shows accelerated divergence across mammals (Oliver et al 2009).…”

The theory and practice of measuring broad-range recombination rate from marker selected pools

“…Since each chromosome, on average, has on average one to two crossovers, large numbers of individuals, and therefore libraries/barcodes, need to be sequenced for a comprehensive map. Given the environmentally-induced volatility (Stern 1926;Neel 1941;Redfield 1966) and inter- (Jensen-Seaman et al 2004;Kulathinal et al 2008;Smukowski and Noor 2011;Brand et al 2018) and intra-specific variability (Nachman 2002;Dumont et al 2009Dumont et al , 2011Comeron et al 2012;Kaur and Rockman 2014) of recombination rates, a scalable high-throughput method of estimation will greatly facilitate our characterization and understanding of recombination.…”