Genetic variation and potential for resistance development to the tTA overexpression lethal system in insects

Release of insect pests carrying the dominant lethal tetracycline transactivator (tTA) overexpression system has been proposed as a means for population suppression. Here we utilized the Drosophila melanogaster Genetic Reference Panel (DGRP) to examine the influence of genetic variation on the efficacy of a female-specific tTA system. We find a surprisingly wide variation in the level of female lethality between DGRP lines. A genome-wide association analysis identified 108 genes associated with high or low lethality, including genes that regulate gene expression. Indeed, we found tTA RNA levels were lower in some of the backgrounds with high female survival. Other backgrounds with high female survival had relatively high tTA levels. In one, RNAseq analysis indicates that expression of genes associated with chitin could be influencing female survival. Our data suggest that standing genetic variation in an insect population could provide multiple mechanisms for resistance to the tTA overexpression system