Extensive recombination suppression and chromosome-wide differentiation of a segregation distorter in Drosophila

Segregation distorters violate Mendelian Inheritance by over-representing themselves in the progeny of carrier individuals and are commonly associated with chromosomal inversions. When distorting alleles are found on sex chromosomes, the progeny of carrier individuals will exhibit skewed sex ratios, as exemplified by the array ofSex-Ratio(SR) distorting chromosomes found in Drosophila. Because of the strong selective pressures such chromosomes are thought to inflict on genomes, segregation distorters and their associated inversions are expected to experience rapid turn-over. However, theSRX-chromosome ofDrosophila pseudoobscurais found at high frequencies in natural populations, forms stable latitudinal clines, appears to be unsuppressed, and shows evidence of being quite long-lived. Despite being a historically significant and well-studied segregation distortion system, the mechanisms allowing for the long-term persistence of theD.pseudoobscura SRchromosome remain unclear. Here, we perform a comparative genomic analysis betweenSRand uninverted standard X-chromosomes inD.pseudoobscurato study its evolutionary history and dynamics. We find a substantial level of differentiation between theSRand standard chromosome and estimate that the associated inversions have likely existed for the entire lifetime of the species (>2 million generations). Through direct recombination experiments and population genetic analyses, we infer that this high level of differentiation is maintained by a combination of suppressed recombination and epistatic selection. Finally, our data reveal a massive mutational target size for protein and expression level changes specific toSRgenerated by its three non-overlapping inversions. Together our results imply that the entireSRchromosome inD.pseudoobscurabehaves as a single co-adapted gene complex and has been maintained through a combination of suppressed recombination and epistatic selection. This finding highlights the dramatic consequences segregation distorters can have in shaping chromosome-wide patterns of recombination, nucleotide variation, and gene expression.