Flexibility in a Gene Network Affecting a Simple Behavior in Drosophila melanogaster

Abstract

Gene interactions are emerging as central to understanding the realization of any phenotype. To probe the flexibility of interactions in a defined gene network, we isolated a set of 16 interacting genes in Drosophila, on the basis of their alteration of a quantitative behavioral phenotype-the loss of coordination in a temperature-sensitive allele of Syntaxin1A. The interactions inter se of this set of genes were then assayed in the presence and in the absence of the original Syntaxin1A mutation to ask whether the relationships among the 16 genes remain stable or differ after a change in genetic context. The pattern of epistatic interactions that occurs within this set of variants is dramatically altered in the two different genetic contexts. The results imply considerable flexibility in the network interactions of genes. CONTEXT is the hallmark of biological processes. among these elements is predominately fixed and predictable. The first assumption-specificity-has come Among the various categories of biological context, much attention has been paid to environment and under increasing scrutiny as more and more genes are found to be pleiotropic, a property that appears to be to historical contingency. These factors have been approached experimentally in studies of norms of reaction particularly prevalent in genes implicated in neural function and behavior (Hall 1994; Greenspan 2001; Sokoand by means of laboratory selection. The discovery early in experimental genetics of epistasis established lowski 2002). In this report, we challenge the second assumption-the stability of relationships in a gene netgenetic context as another important factor and gave rise to the study of interactions among genes.work-in an analysis of interactions among a set of genes affecting loss of coordination in Drosophila melanogaster. Interactions among genes are key to understanding the realization of any phenotype. Although the term "epistaUnlike previous studies of gene networks, we have presis" has meant different things to different people (Phildefined a gene network in terms of functional interlips 1998), the study of gene interactions and networks actions, rather than common phenotype, common biohas been integral to population genetics (Fisher 1918; chemical -interacting EP strains. mosome 1 or 2, were collected. (Representative schemes for Average EP effects were derived from each matrix separately, these crosses can be found in Greenspan 2004.) These were and the "tie-in" matrix (matrix III) provides an independent then crossed with w 1118 females to establish stocks. A total of assessment of the average effects calculated from matrices I 268 such lines were tested, from which 15 were saved, yielding and II. These calculations provide the material for calculating two unique inserts (EP2 and EP7, see Table 2) whose flanking predicted values for each trans-heterozygote pair, with which sequences and genomic position were identified by inverse observed data can be compared and epistasis identified. These PCR (Dalby et a...

Genetic architecture of quantitative traits in mice, flies, and humans

“…The few studies using these designs all reveal extensive epistasis: for metabolic activity (Clark and Wang 1997), olfactory behavior (Fedorowicz et al 1998;Sambandan et al 2006), climbing behavior (van Swinderen and Greenspan 2005), and locomotor startle response (Yamamoto et al 2008). Remarkably, epistatic interactions have also been observed between functional polymorphisms affecting alcohol dehydrogenase protein level within the Adh locus (Stam and Laurie 1996).…”

Neurogenetic networks for startle-induced locomotion in Drosophila melanogaster

“…Because the P[GT1] insertion lines are in isogenic backgrounds, we can examine enhancer and suppressor effects among a subset of these genes, separating dominance effects from epistasis by generating all possible nonreciprocal double heterozygotes (23)(24)(25). We selected 15 representative P[GT1] insertion lines for this analysis based on the following criteria: (i) the P[GT1] insertions were in the Canton-S (B) background; (ii) the P[GT1] insertions were autosomal (to enable complete analysis for both sexes); (iii) the P-elements were inserted within or in proximity to an unambiguously identified gene; and (iv) the P[GT1] insertion had a large effect on the phenotype.…”

“…The specific combining ability (SCA) of a double heterozygote is the deviation of its observed phenotype from that predicted from the GCAs of the parents (26). Significant SCA is due to epistasis, and the direction of the deviation indicates either an enhancer or suppressor effect between the two mutations (23)(24)(25).…”

The implications of gene–environment interactions in depression: will cause inform cure?

“…27 This remarkable adaptability is due to degeneracy: the fact that biological functions can be performed by multiple structurally distinct mechanisms. 27,28 Degeneracy is a ubiquitous property of biological systems that has been upheld through natural selection, as it allows adaptation to unpredictable changes in environment. 27 In a degenerate system, any perturbation is balanced by adaptive changes in other components, minimizing the impact of any single change.…”

“…27 In a degenerate system, any perturbation is balanced by adaptive changes in other components, minimizing the impact of any single change. 28 Importantly, the effect of single gene variation can become manifest under constrained environments, resulting into intriguing differences between laboratory and natural environment or even between different laboratories. 29 An extension of the degeneracy principle to the causation of human disease has two major implications.…”