Convergent Balancing Selection on an Antimicrobial Peptide in Drosophila

Genes of the immune system often evolve rapidly and adaptively, presumably driven by antagonistic interactions with pathogens [1–4]. Those genes encoding secreted antimicrobial peptides (AMPs), however, have failed to exhibit conventional signatures of strong adaptive evolution, especially in arthropods (e.g., [5, 6]) and often segregate for null alleles and gene deletions [3, 4, 7, 8]. Furthermore, quantitative genetic studies have failed to associate naturally occurring polymorphism in AMP genes with variation in resistance to infection [9–11]. Both the lack of signatures of positive selection in AMPs and lack of association between genotype and immune phenotypes have yielded an interpretation that AMP genes evolve under relaxed evolutionary constraint, with enough functional redundancy that variation in, or even loss of, any particular peptide would have little effect on overall resistance [12, 13]. In stark contrast to the current paradigm, we identified a naturally occurring amino acid polymorphism in the AMP Diptericin that is highly predictive of resistance to bacterial infection in Drosophila melanogaster [13]. The identical amino acid polymorphism arose in parallel in the sister species D. simulans, by independent mutation with equivalent phenotypic effect. Convergent substitutions at the same amino acid residue have evolved at least five times across the Drosophila genus. We hypothesize that the alternative alleles are maintained by balancing selection through context-dependent or fluctuating selection. This pattern of evolution appears to be common in AMPs but is invisible to conventional screens for adaptive evolution that are predicated on elevated rates of amino acid divergence. •A convergent polymorphism in an antimicrobial peptide is segregating in Drosophila•The polymorphism is predictive of resistance to bacterial infection in two species•Convergence is observed at this residue five times across the genus Drosophila•Alleles appear to be maintained by balancing selection Unckless et al. identify a convergent amino acid polymorphism in an antimicrobial peptide that is segregating in two species of Drosophila and is predictive of resistance to infection. They observe a high frequency of the alleles in natural populations and convergence across the genus, suggesting the alleles are maintained by balancing selection.