Localization of Candidate Regions Maintaining a Common Polymorphic Inversion (2La) in Anopheles gambiae

Chromosomal inversion polymorphisms are thought to play a role in adaptive divergence, but the genes conferring adaptive benefits remain elusive. Here we study 2La, a common polymorphic inversion in the African malaria vector Anopheles gambiae. The frequency of 2La varies clinally and seasonally in a pattern suggesting response to selection for aridity tolerance. By hybridizing genomic DNA from individual mosquitoes to oligonucleotide microarrays, we obtained a complete map of differentiation across the A. gambiae genome. Comparing mosquitoes homozygous for the 2La gene arrangement or its alternative (2L+(a)), divergence was highest at loci within the rearranged region. In the 22 Mb included within alternative arrangements, two ∼1.5 Mb regions near but not adjacent to the breakpoints were identified as being significantly diverged, a conclusion validated by targeted sequencing. The persistent association of both regions with the 2La arrangement is highly unlikely given known recombination rates across the inversion in 2La heterozygotes, thus implicating selection on genes underlying these regions as factors responsible for the maintenance of 2La. Polymorphism and divergence data are consistent with a model in which the inversion is maintained by migration-selection balance between multiple alleles inside these regions, but further experiments will be needed to fully distinguish between the epistasis (coadaptation) and local adaptation models for the maintenance of 2La.