The genetics of DDT resistance in Drosophila melanogaster: novel insights into an old debate

© 2015 Dr. Joshua Michael SchmidtThe genetics of DDT resistance in Drosophila melanogaster has been a topic of debate for over 60 years. Beginning with James Crow’s observation that his lab selected flies exhibited polygenic inheritance for DDT resistance, the old debate has concerned itself with what mode of inheritance – polygenic or monogenic – best explains DDT resistance in D. melanogaster. The field has had many important contributions, and both the polygenic and monogenic “schools” can muster substantial evidence in their favour. However a reading of the relevant literature, and an appraisal of developments in the field of population genetics should suggest that these seemingly dichotomous views are not mutually exclusive. We may expect to find that DDT resistance factors span a range of effect sizes, some large perhaps many more of smaller effect. The problem has been that very little effort has been deployed in a quantitative analysis of DDT resistance. Instead of asking do x genes confer resistance or not, we should perhaps ask how much of the variation in DDT resistance does each gene explain. While DDT resistance in the majority of resistant D. melanogaster strains can be said to not be monogenic, very few if any resistance genes have been identified with them. In contrast the monogenic school has provided an extensively validated resistance gene, the Cytochrome P450 Cyp6g1. However the old debate about genetic architectures is reflected in a newer debate about Cyp6g1’s contribution to DDT resistance. Can it explain the resistance seen in lab selected strains? Is it only selected in field populations? It would appear that some of this confusion stems from previously undiscovered functional variation at Cyp6g1. The second chapter of this thesis dissects an adaptive allelic series at Cyp6g1, and determines that it contributes greatly to variation in DDT resistance in field populations. However it can only explain half the genetic variation in DDT resistance at most. The third chapter of this thesis reports on a Genome Wide Association Study for DDT resistance in another D. melanogaster population that identifies novel DDT resistance genes, but perhaps paradoxically finds that Cyp6g1 does not contribute to DDT resistance in this population. Previously such an observation would provide grist for the mill in minimising Cyp6g1’s role in DDT resistance. However a quantitative genetics approach suggests that this discrepancy merely reflects that fact that resistance alleles of Cyp6g1 have already swept through most populations of D. melanogaster – it was but is no longer a DDT resistance factor in some populations. In contrast the newly identified DDT resistance loci do not bear the footprints of recent positive selection. This result neatly demonstrates the difference between the genetic basis of standing variation versus the adaptive response, but also points to the challenge in identifying a polygenic signal of adaptation in the background of a strong single gene sweep