Non-uniform chromosomal SNP density biases sites of meiotic crossovers in Drosophila melanogaster

Here we localize a genetic suppressor that enhances the reduced locomotor activity phenotype of flies lacking brain dopamine. We utilized a bulk segregant analysis mapping strategy coupled with whole genome sequencing, mapping the trait to a roughly 3.5 mega-base region of the X chromosome. However, this mapping yielded ∼5-fold lower resolution than anticipated, due to an uneven distribution of single nucleotide polymorphisms (SNPs) between the X chromosomes of the 2 recombining lines. This uneven SNP distribution was associated with recombination events biased toward regions of low SNP density, and away from the more SNP dense regions associating with the activity phenotype. We find that nearly perfect mapping of X chromosome visible markers occurs only in historical data from a time before the establishment of discrete genetic background strains. This suggests that genetic uniformity in early Drosophila studies may have contributed to more consistent recombination frequencies, whereas modern mapping efforts are complicated by variability in SNP distribution across recombining strains. These findings highlight challenges in Drosophila genetic mapping in situations where altered SNP density can skew recombination, complicating trait localization.