Overdominance for fitness: a genomic comparison between empirical and simulated data with Drosophila melanogaster

Overdominance (heterozygote advantage) for fitness is a form of balancing selection which supports the maintenance of genetic polymorphisms in the populations. This mode of selection is expected to generate a conspicuous footprint on neutral genetic variation in genomic regions of restricted recombination, which contrasts with the signature generated by other types of natural selection. In particular, gene diversity is expected to be increased at neutral sites tightly linked to overdominant sites, as opposed to background selection and selective sweeps. We produced extensive whole-genome sequencing data to analyze genetic diversity across regions exhibiting varying recombination patterns in a Drosophila melanogaster population with known demographic history. The results were compared with simulation data in order to quantify the magnitude of the contribution of overdominant loci to genetic diversity which could be compatible with observations. We analyzed sequencing data from 51 individual male flies sampled from a large population and estimated the average nucleotide diversity (π) in 100-kb consecutive windows across the main autosomal chromosomes. By using the available recombination map in the species, we evaluated the changes in π in relation with the levels of recombination across genomic regions. We then carried out computer simulations following the demographic history, the genomic architecture and the recombination map of the main autosomal chromosomes assuming models which include deleterious (background selection) and advantageous (selective sweeps) mutations, or models also including increasing rates of overdominant mutations. By comparing the results obtained from simulations and the observed data, we conclude that a parsimonious model of background selection and adaptation to captivity explains the observed patterns of neutral variation in the studied population better than the models including overdominance.