Variation and evolution of the glutamine-rich repeat region of Drosophila Argonaute-2

RNA interference pathways mediate multiple biological processes through Argonaute-family proteins, which bind small RNAs as guides to silence complementary target nucleic acids. In insects and crustaceans, Argonaute-2 silences viral nucleic acids, and therefore acts as a primary effector of innate antiviral immunity. Although the function of the major of Argonaute-2 domains, which are conserved across most Argonaute-family proteins, are known, many invertebrate Argonaute-2 homologs contain a glutamine-rich repeat (GRR) region of unknown function at the N-terminus. Here we combine long-read amplicon sequencing of Drosophila Genetic Reference Panel (DGRP) lines with publicly available sequence data from many insect species to show that this region evolves extremely rapidly and is hypervariable within species. We identify distinct GRR haplotype groups in D. melanogaster , and suggest that one of these haplotype groups has recently risen to high frequency in North American populations. Finally, we use published data from genome-wide association studies of viral resistance in D. melanogaster to test whether GRR haplotypes are associated with survival after virus challenge. We find a marginally significant association with survival after challenge with Drosophila C Virus in the DGRP, but we were unable to replicate this finding using lines from the Drosophila Synthetic Population Resource panel.