The project proposed here will determine the molecular genetic control of evolved differences in the genomic recombination landscape between Drosophila species. The total genetic map of D. mauritiana is ~1.7 times longer than that of D. melanogaster-implying nearly twice as many crossovers per meiosis- and the extent of centromeric and telomeric suppression of crossing over is considerably smaller in D. mauritiana than D. melanogaster. In preliminary work, we showed that a dicistronic gene, mei-217/mei-218, has a history of recurrent adaptive evolution and mediates this evolved species difference in genetic map length. Here we propose to further investigate mei-217/mei-218 in three ways. First, we will functionally dissect the mei- 217/mei-218 gene, using interspecific chimeric transgene constructs, to determine which functional domains contribute to the evolutionary change in recombination rate. MEI-217 and MEI-218 have predicted DNA- binding domains and participate in a putative complex of minichromosome maintenance (MCM) proteins- along with MCM5 and REC/MCM8- required for the formation and/or stabilization of heteroduplex DNA crossover intermediates during meiotic recombination. Our functional dissection of mei-217/mei-218 may therefore shed light on how the gene products alter the probability of successful crossover formation. Second, we will use multiplexed next-generation sequencing to obtain and compare high-resolution genomic maps of crossing over and gene conversion between transgenic D. melanogaster genotypes that differ only in carrying either the D. melanogaster or D. mauritiana allele of mei-217/mei-218. With these data, we will determine the basis of species differences in the rate and distribution of crossover events. Finally, we will use our D. melanogaster system to assay the effects of functional divergence in mei-217/mei-218 to ask if recurrent substitutions in this rapidly evolving gene mediate changes in recombination rate in other Drosophila lineages.
The work described here focuses on two proteins essential for recombination and repair of DNA double-strand breaks during meiosis, the cell divisions preceding the formation eggs. This work may therefore further our understanding of one aspect of basic transmission genetics. In most species, including humans, the disruption of meiotic recombination and repair is a cause of infertility and harmful mutations.
| Brand, Cara L; Cattani, M Victoria; Kingan, Sarah B et al. (2018) Molecular Evolution at a Meiosis Gene Mediates Species Differences in the Rate and Patterning of Recombination. Curr Biol 28:1289-1295.e4 |
