A single amino acid polymorphism in natural Metchnikowin alleles of Drosophila results in systemic immunity and life history tradeoffs

Antimicrobial peptides (AMPs) are small peptides produced by many living organisms as a frontline immune response to a variety of microbial pathogens. These peptides directly interface with pathogens to kill them shortly after infection. Importantly, multiple AMP alleles can be balanced within a population, but little is known about how this immune variation among individuals is maintained over time. Multiple species of Drosophila balance two specific alleles of the AMP, Metchnikowin (Mtk), a canonically antifungal and antibacterial peptide. Here, various life-history and infection assays assess the mechanism of Metchnikowin balancing selection using CRISPR-generated D. melanogaster with a null mutation or either of the two alleles, MtkR or MtkP. Findings demonstrate that the MtkR allele usually confers greater protection than the MtkP allele in males, but carries a fitness cost without infection. However, this pattern flips in females with certain infections, with the MtkP allele conferring greater protection than MtkR. This suggests that the two alleles are repeatedly maintained in fly populations due to differential fitness of hosts in the context of many variables including host genotype, sex, infection status, and pathogen species. It also suggests that maintenance of immune variation in a population can be based on just a single amino acid difference between individuals. This data is from sequencing our CRISPRed lines.