title: Epistasis dominates the genetic architecture of Drosophila quantitative traits.
abstract: Epistasis-nonlinear genetic interactions between polymorphic loci-is the genetic basis of canalization and speciation, and epistatic interactions can be used to infer genetic networks affecting quantitative traits. However, the role that epistasis plays in the genetic architecture of quantitative traits is controversial. Here, we compared the genetic architecture of three Drosophila life history traits in the sequenced inbred lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) and a large outbred, advanced intercross population derived from 40 DGRP lines (Flyland). We assessed allele frequency changes between pools of individuals at the extremes of the distribution for each trait in the Flyland population by deep DNA sequencing. The genetic architecture of all traits was highly polygenic in both analyses. Surprisingly, none of the SNPs associated with the traits in Flyland replicated in the DGRP and vice versa. However, the majority of these SNPs participated in at least one epistatic interaction in the DGRP. Despite apparent additive effects at largely distinct loci in the two populations, the epistatic interactions perturbed common, biologically plausible, and highly connected genetic networks. Our analysis underscores the importance of epistasis as a principal factor that determines variation for quantitative traits and provides a means to uncover genetic networks affecting these traits. Knowledge of epistatic networks will contribute to our understanding of the genetic basis of evolutionarily and clinically important traits and enhance predictive ability at an individualized level in medicine and agriculture.
authors.affiliation: Department of Genetics, North Carolina State University, Raleigh, NC 27695, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Huang
authors.forename: Stephen
authors.initials: S
authors.lastname: Richards
authors.forename: Mary Anna
authors.initials: MA
authors.lastname: Carbone
authors.forename: Dianhui
authors.initials: D
authors.lastname: Zhu
authors.forename: Robert R H
authors.initials: RR
authors.lastname: Anholt
authors.forename: Julien F
authors.initials: JF
authors.lastname: Ayroles
authors.forename: Laura
authors.initials: L
authors.lastname: Duncan
authors.forename: Katherine W
authors.initials: KW
authors.lastname: Jordan
authors.forename: Faye
authors.initials: F
authors.lastname: Lawrence
authors.forename: Michael M
authors.initials: MM
authors.lastname: Magwire
authors.forename: Crystal B
authors.initials: CB
authors.lastname: Warner
authors.forename: Kerstin
authors.initials: K
authors.lastname: Blankenburg
authors.forename: Yi
authors.initials: Y
authors.lastname: Han
authors.forename: Mehwish
authors.initials: M
authors.lastname: Javaid
authors.forename: Joy
authors.initials: J
authors.lastname: Jayaseelan
authors.forename: Shalini N
authors.initials: SN
authors.lastname: Jhangiani
authors.forename: Donna
authors.initials: D
authors.lastname: Muzny
authors.forename: Fiona
authors.initials: F
authors.lastname: Ongeri
authors.forename: Lora
authors.initials: L
authors.lastname: Perales
authors.forename: Yuan-Qing
authors.initials: YQ
authors.lastname: Wu
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zou
authors.forename: Eric A
authors.initials: EA
authors.lastname: Stone
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.forename: Trudy F C
authors.initials: TF
authors.lastname: Mackay
mesh_terms: D000818:Animals; D004331:Drosophila melanogaster; D004843:Epistasis, Genetic / Q000502:physiology*; D017344:Genes, Insect / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable