Epistasis is an integral feature of the genetic architecture of quantitative traits (Anholt & Mackay, 2004
; Flint & Mackay, 2009
; Mackay et al.
). Epistasis occurs when the effect of variation at one locus is suppressed or enhanced by the genotype at another locus. Epistatic interactions can bias estimates of the effects of quantitative trait loci (QTLs) in mapping populations when present but not accounted for (Carlborg et al.
); enable inferences of genetic networks affecting complex traits (Phillips, 2008
); and affect predictions of long-term response to artificial and natural selection (Carlborg et al.
; Phillips, 2008
). Epistasis is difficult to detect in classical quantitative genetic analyses based on resemblance between relatives in outbred populations (Falconer & Mackay, 1996
), and epistatic interactions contribute largely additive genetic variation in outbred populations when the contributing alleles are rare (Hill et al.
). However, epistatic interactions are common in experiments designed to examine their effects on trait means in QTL mapping populations. For example, in Drosophila
epistatic interactions have been reported between QTLs affecting bristle number (Long et al.
; Gurganus et al.
; Dilda & Mackay, 2002
), wing morphology (Weber et al.
), lifespan (Leips & Mackay, 2000
) and startle-induced locomotor behaviour (Jordan et al.
). In mice, epistasis has been reported between QTLs affecting growth, body weight and morphometry (Brockmann et al.
; Cheverud et al.
; Workman et al.
; Klingenberg et al.
; Yi et al.
). Epistasis is also a prominent feature of the genetic architecture of growth rate in Arabidopsis
(Kroymann & Mitchell-Olds, 2005
), chickens (Carlborg et al.
) and yeast (Steinmetz et al.
; Sinha et al.
Although epistatic interactions have been detected in QTL mapping experiments, it is easier to study epistasis in crosses among lines with reduced genetic heterogeneity in largely homozygous genetic backgrounds (Eshed & Zamir, 1996
; Clark & Wang, 1997
; Sambandan et al.
). Drosophila melanogaster
is an excellent model system to study epistasis affecting quantitative traits due to the ease of constructing chromosome substitution and introgression lines, and generating mutations in a common homozygous genotype. Epistasis has been documented for aggressive behaviour by constructing chromosome substitution lines in which small segments of one genotype were introgressed into a different genetic background (Edwards & Mackay, 2009
). Epistasis for aggression was also evident from behavioural and whole genome transcriptional analyses of an ensemble of co-isogenic hyper-aggressive P
-element insertion lines (Zwarts et al.
). Epistasis for metabolic activity was revealed by constructing all possible two-locus genotypes for several pairs of P-
element insertion mutations (Clark & Wang, 1997
). Diallel cross analysis of co-isogenic P
-element insertion lines enabled identification of epistatic networks of genes affecting negative geotaxis (Van Swinderen & Greenspan, 2005
), olfactory avoidance behaviour (Fedorowicz et al.
; Sambandan et al.
), aggression (Zwarts et al.
) and startle behaviour in Drosophila
(Yamamoto et al.
Previously, Yamamoto et al.
) created pairs of chromosome substitution lines in which isogenic Canton
) chromosomes with P-
element insertions in genes affecting startle behaviour and their P
-element free co-isogenic control chromosomes were substituted into different homozygous wild-derived D. melanogaster
genotypes. This design enables the quantification of the extent to which naturally segregating variants modify the effects of single mutations, as well as the magnitude of variation of epistasis among the different lines. This study reported widespread suppressing epistasis of naturally segregating modifiers on startle behaviour. Since the magnitude of suppressing epistasis was proportional to the magnitude of the mutational effect of the P
-element insertion on startle behaviour, it was concluded that suppressing epistasis buffers the effects of new mutations in natural populations.
-element insertions at genes previously implicated in startle behaviour, Semaphorin-5C
) and Calreticulin
) also affect olfactory behaviour (Sambandan et al.
) and in the case of Crc
, sleep phenotypes (Harbison & Sehgal, 2008
). The objective of the present study was to ask whether suppressing epistasis by naturally segregating modifiers on behavioural traits is a general principle or unique to the startle response, and, moreover, to assess whether the effects of the same P
-element insertion on different phenotypes is modulated by the same or different epistatic modifiers.