The Genetic Architecture of Natural Variation in Recombination Rate in Drosophila melanogaster

Meiotic recombination ensures proper chromosome segregation in many sexually reproducing organisms. Despite this crucial function, rates of recombination are highly variable within and between taxa, and the genetic basis of this variation remains poorly understood. Here, we exploit natural variation in the inbred, sequenced lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) to map genetic variants affecting recombination rate. We used a two-step crossing scheme and visible markers to measure rates of recombination in a 33 cM interval on the X chromosome and in a 20.4 cM interval on chromosome 3R for 205 DGRP lines. Though we cannot exclude that some biases exist due to viability effects associated with the visible markers used in this study, we find ~2-fold variation in recombination rate among lines. Interestingly, we further find that recombination rates are uncorrelated between the two chromosomal intervals. We performed a genome-wide association study to identify genetic variants associated with recombination rate in each of the two intervals surveyed. We refined our list of candidate variants and genes associated with recombination rate variation and selected twenty genes for functional assessment. We present strong evidence that five genes are likely to contribute to natural variation in recombination rate in D. melanogaster; these genes lie outside the canonical meiotic recombination pathway. We also find a weak effect of Wolbachia infection on recombination rate and we confirm the interchromosomal effect. Our results highlight the magnitude of population variation in recombination rate present in D. melanogaster and implicate new genetic factors mediating natural variation in this quantitative trait.
Author Summary During meiosis, homologous chromosomes exchange genetic material through recombination. In most sexually reproducing species, recombination is necessary for chromosomes to properly segregate. Recombination defects can generate gametes with an incorrect number of chromosomes, which is devastating for organismal fitness. Despite the central role of recombination for chromosome segregation, recombination is highly variable process both within and between species. Though it is clear that this variation is due at least in part to genetics, the specific genes contributing to variation in recombination within and between species remain largely unknown. This is particularly true in the model organism, Drosophila melanogaster. Here, we use the D. melanogaster Genetic Reference Panel to determine the scale of population-level variation in recombination rate and to identify genes significantly associated with this variation. We estimated rates of recombination on two different chromosomes in 205 strains of D. melanogaster. We also used genome-wide association mapping to identify genetic factors associated with recombination rate variation. We find that recombination rate on the two chromosomes are independent traits. We further find that population-level variation in recombination is mediated by many loci of small effect, and that the genes contributing to variation in recombination rate are outside of the well-characterized meiotic recombination pathway.