Resequencing of Drososophila melanogaster populations,selected for increased DCV resistance.

Host adaptation to one parasite may affect its response to others. Yet, the genetics of these direct and correlated responses remain poorly studied. The overlap between these responses is instrumental for the understanding of host evolution in multi-parasite environments. We determined the genetic and phenotypic changes underlying adaptation of Drosophila melanogaster to Drosophila C virus (DCV). Within 20 generations, flies selected with DCV showed increased survival after DCV infection, but also after Cricket Paralysis Virus (CrPV) and Flock House Virus (FHV) infection. Whole-genome sequencing identified two regions of significant differentiation among treatments, from which candidate genes were functionally tested with RNAi. Three genes were validated, pst, a known DCV-response gene, and two novel loci: Ubc-E2H and CG8492. Knockdown of Ubc-E2H and pst also led to increased sensitivity to CrPV, while knockdown of CG8492 increased susceptibility to FHV infection. Therefore, Drosophila adaptation to DCV relies on few major genes, each with different cross-resistance properties, conferring host resistance to several parasites.