Complex genetic architecture of
            <i>Drosophila</i>
            aggressive behavior

Zwarts, Liesbeth; Magwire, Michael M.; Carbone, Mary Anna; Versteven, Marijke; Herteleer, Liesbet; Anholt, Robert R. H.; Callaerts, Patrick; Mackay, Trudy F. C.

doi:10.1073/pnas.1113877108

Cited by 70 publications

(72 citation statements)

References 45 publications

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“…The effects of Drosophila mutations (33) and natural variants (37) on aggression depend on genetic background, a phenomenon also observed for mutations in neuronal nitric oxide synthase (38) and Nr2e1 (16) in mice. Analysis of naturally segregating variation can leverage polymorphisms at many loci to explore the contribution of epistatic interactions to genetic variation for complex traits (39)(40)(41).…”

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confidence: 99%

“…The cuticular hydrocarbon (z)-7-tricosene is also required for male−male aggression; this effect is modulated via gustatory receptor neurons expressing Gr32a (30). Unbiased mutagenesis screens for genes affecting aggressive behavior (31) and transcriptional profiling of mutations (32,33), artificial selection lines (34,35), and wild-derived inbred lines (36) divergent for aggressive behavior have implicated hundreds of genes spanning diverse biological processes.…”

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confidence: 99%

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Genetic architecture of natural variation in Drosophila melanogaster aggressive behavior

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Couch

Huang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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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 CO 2 , 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.Drosophila Genetic Reference Panel | genome-wide association mapping | extreme QTL mapping | advanced intercross population | epistasis A ggression is a near-universal animal behavior, important for securing food resources, defense against predators, gaining access to mating partners and, among social animals, creating and maintaining dominance hierarchies. Aggressive behavior is a typical quantitative trait, with natural variation attributable to segregating variants at multiple interacting loci, the effects of which are sensitive to the physical and social environments to which the individuals are exposed (1). Sociopathic and violent behaviors place a significant socioeconomic burden on human societies. However, disentangling the relative genetic and environmental contributions to aggressive behavior in natural populations is challenging due to its low heritability, and, in humans, because of the difficulty in accounting for social and other environmental influences, precisely quantifying aggression, and comorbidity with other psychological disorders.These challenges can be overcome using animal models. Numerous studies have highlighted the evolutionary conservation of neural pathways affecting aggression (2-4). Genes affecting bioamine signaling affect aggressive behavior in humans (4, 5), mice (6-8), and Drosophila (9-15). The nuclear receptor subfamily 2, group E, member 1 gene Nr2e1 affects aggressiv...

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confidence: 99%

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confidence: 99%

Genetic architecture of natural variation in Drosophila melanogaster aggressive behavior

Shorter

Couch

Huang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

130

115

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“…Cost-effective epigenetic and physiological models are needed for (i) addressing tissue-specific responses to toxins, (ii) gaining insights into mechanisms of epigenetic toxicity, and (iii) evaluating the manifestation of these responses across naturally occurring genotypes. In particular, cost-effective models with massive publicly available genetic information (Zwarts et al 2011;King et al 2012a,b;Mackay et al 2012) might allow for genome-wide evaluation of toxic responses and assessment of coexposure outcomes in conjunction with the evaluation of unique individual responses.…”

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confidence: 99%

High Intake of Dietary Sugar Enhances Bisphenol A (BPA) Disruption and Reveals Ribosome-Mediated Pathways of Toxicity

Branco¹,

Lemos²

2014

Genetics

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Bisphenol A (BPA) is an organic compound to which human populations are ubiquitously exposed. Epidemiological data suggest BPA exposure might be associated with higher rates of diabetes and reproductive anomalies. Health concerns also include transgenerational consequences, but these mechanisms are crudely defined. Similarly, little is known about synergistic interactions between BPA and other substances. Here we show that acute and chronic exposure to BPA causes genome-wide modulation of several functionally coherent genetic pathways in the fruit fly Drosophila melanogaster. In particular, BPA exposure causes massive downregulation of testis-specific genes and upregulation of ribosome-associated genes widely expressed across tissues. In addition, it causes the modulation of transposable elements that are specific to the ribosomal DNA loci, suggesting that nucleolar stress might contribute to BPA toxicity. The upregulation of ribosome-associated genes and the impairment of testis-specific gene expression are significantly enhanced upon BPA exposure with a high-sugar diet. Our results suggest that BPA and dietary sugar might functionally interact, with consequences to regulatory programs in both reproductive and somatic tissues. E XPOSURE to environmental toxins is widespread. It is well documented, for instance, that human populations are commonly exposed to bisphenol A (BPA), bis(2-ethylhexyl) phthalate (DEHP), dioxins, and other organic molecules produced at industrial scales. Toxins might act by modulating epigenetic pathways to change the expression of genes and normal cellular homeostasis and could result in transgenerational consequences. The fast pace at which new compounds are invented and become ubiquitous in the environment poses a challenge to safety assessment. This challenge emerges not only from the large number of compounds to evaluate, but also from the high dimensionality of toxic responses across tissue types and developmental stages. This is further aggravated by the potential for unexpected synergism among toxins in mixtures. Sensitivity might also be strongly dependent on the specific epigenomic features and genetic makeup of an individual (Du et al. 2004).Genomic analyses have uncovered levels of human genetic variation not surmised a few decades ago (e.g., Sudmant et al. 2010). Cost-effective epigenetic and physiological models are needed for (i) addressing tissue-specific responses to toxins, (ii) gaining insights into mechanisms of epigenetic toxicity, and (iii) evaluating the manifestation of these responses across naturally occurring genotypes. In particular, cost-effective models with massive publicly available genetic information (Zwarts et al. 2011; King et al. 2012a,b;Mackay et al. 2012) might allow for genome-wide evaluation of toxic responses and assessment of coexposure outcomes in conjunction with the evaluation of unique individual responses.BPA is one of the most abundantly produced chemicals worldwide, reaching an annual volume .4 million tons (Burridge 2003). Multi...

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“…Indeed, a recent study identified up-and downregulation of more than 4,038 genes in differences in aggression in fruit flies (Zwarts et al 2011). It is not sufficient, however, to pay lip service to the existence of such extreme polygenicity and environmental interaction and then defend the plausibility of resultsthat a single polymorphism can predict a behavior such as voter turnout-that directly contradict those same principles.…”

Section: Responses To a Few Objectionsmentioning

confidence: 99%