title: Genetic architecture of natural variation in Drosophila melanogaster aggressive behavior.
abstract: Aggression is an evolutionarily conserved complex behavior essential for survival and the organization of social hierarchies. With the exception of genetic variants associated with bioamine signaling, which have been implicated in aggression in many species, the genetic basis of natural variation in aggression is largely unknown. Drosophila melanogaster is a favorable model system for exploring the genetic basis of natural variation in aggression. Here, we performed genome-wide association analyses using the inbred, sequenced lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) and replicate advanced intercross populations derived from the most and least aggressive DGRP lines. We identified genes that have been previously implicated in aggressive behavior as well as many novel loci, including gustatory receptor 63a (Gr63a), which encodes a subunit of the receptor for CO2, and genes associated with development and function of the nervous system. Although genes from the two association analyses were largely nonoverlapping, they mapped onto a genetic interaction network inferred from an analysis of pairwise epistasis in the DGRP. We used mutations and RNAi knock-down alleles to functionally validate 79% of the candidate genes and 75% of the candidate epistatic interactions tested. Epistasis for aggressive behavior causes cryptic genetic variation in the DGRP that is revealed by changing allele frequencies in the outbred populations derived from extreme DGRP lines. This phenomenon may pertain to other fitness traits and species, with implications for evolution, applied breeding, and human genetics.
authors.affiliation: Department of Biological Sciences, Program in Genetics and W. M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, NC 27695-7614.
authors.forename: John
authors.initials: J
authors.lastname: Shorter
authors.affiliation: Department of Biological Sciences, Program in Genetics and W. M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, NC 27695-7614.
authors.forename: Charlene
authors.initials: C
authors.lastname: Couch
authors.affiliation: Department of Biological Sciences, Program in Genetics and W. M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, NC 27695-7614.
authors.forename: Wen
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Biological Sciences, Program in Genetics and W. M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, NC 27695-7614.
authors.forename: Mary Anna
authors.initials: MA
authors.lastname: Carbone
authors.affiliation: Department of Biological Sciences, Program in Genetics and W. M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, NC 27695-7614.
authors.forename: Jason
authors.initials: J
authors.lastname: Peiffer
authors.affiliation: Department of Biological Sciences, Program in Genetics and W. M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, NC 27695-7614.
authors.forename: Robert R H
authors.initials: RR
authors.lastname: Anholt
authors.affiliation: Department of Biological Sciences, Program in Genetics and W. M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, NC 27695-7614 trudy_mackay@ncsu.edu.
authors.forename: Trudy F C
authors.initials: TF
authors.lastname: Mackay
mesh_terms: D000374:Aggression; D000818:Animals; D003433:Crosses, Genetic; D029721:Drosophila Proteins / Q000235:genetics* / Q000502:physiology; D004331:Drosophila melanogaster / Q000145:classification / Q000235:genetics* / Q000502:physiology; D004843:Epistasis, Genetic; D019143:Evolution, Molecular; D017344:Genes, Insect / Q000235:genetics* / Q000502:physiology; D014644:Genetic Variation; D049750:Genome, Insect / Q000235:genetics; D006801:Humans; D007178:Inbreeding; D009154:Mutation; D034622:RNA Interference; D013045:Species Specificity
chemical_list: D029721:Drosophila Proteins; C516368:Gr63a protein, Drosophila
keywords: Drosophila Genetic Reference Panel; advanced intercross population; epistasis; extreme QTL mapping; genome-wide association mapping