Epistatic partners of neurogenic genes modulate Drosophila olfactory behavior

• Published in: Genes, brain and behavior Vol. 15; no. 2; pp. 280 - 290
• Main Authors: He, X., Zhou, S., St. Armour, G. E., Mackay, T. F. C., Anholt, R. R. H.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2016; John Wiley & Sons, Inc
• Subjects: Animals; Behavior; Behavior, Animal - physiology; Chemosensation; Drosophila melanogaster; Drosophila melanogaster - genetics; Drosophila melanogaster - physiology; Drosophila melanogaster Genetic Reference Panel; Epistasis, Genetic - genetics; Gene loci; Genes, Insect - genetics; genetic architecture; Genetic Variation - genetics; Genome-Wide Association Study; Genomes; Genotype; Insects; Mutation - genetics; Olfactory Bulb - physiology; Original; Phenotype; quantitative traits; quantitative traits; genetic architecture; Chemosensation; genome-wide association study; Drosophila melanogaster Genetic Reference Panel
• ISSN: 1601-1848; 1601-183X; 1601-183X
• DOI: 10.1111/gbb.12279

The extent to which epistasis affects the genetic architecture of complex traits is difficult to quantify, and identifying variants in natural populations with epistatic interactions is challenging. Previous studies in Drosophila implicated extensive epistasis between variants in genes that affect neural connectivity and contribute to natural variation in olfactory response to benzaldehyde. In this study, we implemented a powerful screen to quantify the extent of epistasis as well as identify candidate interacting variants using 203 inbred wild‐derived lines with sequenced genomes of the Drosophila melanogaster Genetic Reference Panel (DGRP). We crossed the DGRP lines to P[GT1]‐element insertion mutants in Sema‐5c and neuralized (neur), two neurodevelopmental loci which affect olfactory behavior, and to their coisogenic wild‐type control. We observed significant variation in olfactory responses to benzaldehyde among F1 genotypes and for the DGRP line by mutant genotype interactions for both loci, showing extensive nonadditive genetic variation. We performed genome‐wide association analyses to identify the candidate modifier loci. None of these polymorphisms were in or near the focal genes; therefore, epistasis is the cause of the nonadditive genetic variance. Candidate genes could be placed in interaction networks. Several candidate modifiers are associated with neural development. Analyses of mutants of candidate epistatic partners with neur (merry‐go‐round (mgr), prospero (pros), CG10098, Alhambra (Alh) and CG12535) and Sema‐5c (CG42540 and bruchpilot (brp)) showed aberrant olfactory responses compared with coisogenic controls. Thus, integrating genome‐wide analyses of natural variants with mutations at defined genomic locations in a common coisogenic background can unmask specific epistatic modifiers of behavioral phenotypes. Integrating analysis of natural variants with mutations at defined genomic locations can unmask epistatic modifiers of behaviors.