Recurrent loss of an immunity gene that protects Drosophila against a major natural parasite

Polymorphisms in immunity genes can have large effects on susceptibility to infection. To understand the origins of this variation, we investigated the genetic basis of resistance to the parasitoid wasp Leptopilina boulardi in Drosophila melanogaster. A cis-regulatory polymorphism in the gene Lectin-24A abolishes expression after infection, strongly reducing survival. Other null mutations have arisen repeatedly in this gene, with additional loss-of-expression and premature stop codons segregating in nature. The frequency of these alleles varies greatly, and in some populations natural selection has driven them near to fixation. We conclude that there is a pleiotropic cost to Lectin-24A expression, and in some populations this outweighs the benefit of resistance, resulting in natural selection causing the repeated loss of this important immune defense. Significance StatementGenetic differences between individuals can have a large effect on susceptibility to infectious disease. We have identified a gene called Lectin-24A that is important in the immune response that protects fruit flies against one of their main natural enemies--parasitic wasps. However, in nature many flies carry mutated copies of this gene that are no longer functional. We found that the high frequency of these loss-of-function mutations can only be explained if they have a selective advantage in some populations. Therefore, we can conclude that this immune defiance is costly, and genetic variation in susceptibility is maintained because in some locations susceptible flies are fitter than resistant flies.