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 non-bulked segregant analysis using whole genome sequencing (WGS), mapping the trait to a roughly 3.5 mega-base (Mb) 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 two recombining lines. This uneven SNP distribution was associated with recombination events biased towards 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. Article SummaryGenetic mapping studies generally assume uniform crossover distribution across chromosomes. However, this study demonstrates that an uneven density of single nucleotide polymorphism (SNP) is associated with biased sites of meiotic recombination. Using brain dopamine-deficient Drosophila, SNP dense regions show reduced crossover frequency, which reduced the mapping resolution, complicating genetic trait localization. These findings highlight the need to consider parental chromosome SNP distribution and its impact on recombination when designing genetic mapping studies. Future studies should consider chromosome structure, parental haplotype, and sequence heterogeneity to enhance mapping accuracy and resolution.