Genetic Networks Underlying Natural Variation in Basal and Induced Activity Levels in Drosophila melanogaster

Exercise is recommended by health professionals across the globe as part of a healthy lifestyle to prevent and/or treat the consequences of obesity. While overall, the health benefits of exercise and an active lifestyle are well understood, very little is known about how genetics impacts an individual’s inclination for and response to exercise. To address this knowledge gap, we investigated the genetic architecture underlying natural variation in activity levels in the model system Drosophila melanogaster. Activity levels were assayed in the Drosophila Genetics Reference Panel fly strains at baseline and in response to a gentle exercise treatment using the Rotational Exercise Quantification System. We found significant, sex-dependent variation in both activity measures and identified over 100 genes that contribute to basal and induced exercise activity levels. This gene set was enriched for genes with functions in the central nervous system and in neuromuscular junctions and included several candidate genes with known activity phenotypes such as flightlessness or uncoordinated movement. Interestingly, there were also several chromatin proteins among the candidate genes, two of which were validated and shown to impact activity levels. Thus, the study described here reveals the complex genetic architecture controlling basal and exercise-induced activity levels in D. melanogaster and provides a resource for exercise biologists.

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Genetic networks underlying natural variation in basal and induced activity levels in Drosophila melanogaster

10.1101/444380 ◽

2018 ◽

Author(s):

Louis P. Watanabe ◽

Cameron Gordon ◽

Mina Y. Momeni ◽

Nicole C. Riddle

Keyword(s):

Drosophila Melanogaster ◽

Candidate Genes ◽

Genetic Architecture ◽

Natural Variation ◽

Neuromuscular Junctions ◽

Healthy Lifestyle ◽

Activity Levels ◽

Exercise Activity ◽

The Central Nervous System ◽

Exercise Induced

ABSTRACTExercise is recommended by health professionals across the globe as part of a healthy lifestyle to prevent and/or treat the consequences of obesity. While overall, the health benefits of exercise and an active lifestyle are well understood, very little is known about how genetics impacts an individual’s inclination for and response to exercise. To address this knowledge gap, we investigated the genetic architecture underlying natural variation in activity levels in the model system Drosophila melanogaster. Activity levels were assayed in the Drosophila Genetics Reference Panel 2 fly strains at baseline and in response to a gentle exercise treatment using the Rotational Exercise Quantification System. We found significant, sex-dependent variation in both activity measures and identified over 100 genes that contribute to basal and induced exercise activity levels. This gene set was enriched for genes with functions in the central nervous system and in neuromuscular junctions and included several candidate genes with known activity phenotypes such as flightlessness or uncoordinated movement. Interestingly, there were also several chromatin proteins among the candidate genes, two of which were validated and shown to impact activity levels. Thus, the study described here reveals the complex genetic architecture controlling basal and exercise-induced activity levels in D. melanogaster and provides a resource for exercise biologists.

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Genetic architecture of natural variation in visual senescence in Drosophila

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1613833113 ◽

2016 ◽

Vol 113 (43) ◽

pp. E6620-E6629 ◽

Cited By ~ 25

Author(s):

Mary Anna Carbone ◽

Akihiko Yamamoto ◽

Wen Huang ◽

Rachel A. Lyman ◽

Tess Brune Meadors ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Genetic Variation ◽

Life Span ◽

Candidate Genes ◽

Natural Variation ◽

Genetic Basis ◽

Nervous System Development ◽

Interindividual Variation ◽

Human Populations ◽

Age Dependent

Senescence, i.e., functional decline with age, is a major determinant of health span in a rapidly aging population, but the genetic basis of interindividual variation in senescence remains largely unknown. Visual decline and age-related eye disorders are common manifestations of senescence, but disentangling age-dependent visual decline in human populations is challenging due to inability to control genetic background and variation in histories of environmental exposures. We assessed the genetic basis of natural variation in visual senescence by measuring age-dependent decline in phototaxis using Drosophila melanogaster as a genetic model system. We quantified phototaxis at 1, 2, and 4 wk of age in the sequenced, inbred lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) and found an average decline in phototaxis with age. We observed significant genetic variation for phototaxis at each age and significant genetic variation in senescence of phototaxis that is only partly correlated with phototaxis. Genome-wide association analyses in the DGRP and a DGRP-derived outbred, advanced intercross population identified candidate genes and genetic networks associated with eye and nervous system development and function, including seven genes with human orthologs previously associated with eye diseases. Ninety percent of candidate genes were functionally validated with targeted RNAi-mediated suppression of gene expression. Absence of candidate genes previously implicated with longevity indicates physiological systems may undergo senescence independent of organismal life span. Furthermore, we show that genes that shape early developmental processes also contribute to senescence, demonstrating that senescence is part of a genetic continuum that acts throughout the life span.

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Integration of GWAS and TWAS to elucidate the genetic architecture of natural variation for leaf cuticular conductance in maize

10.1101/2021.10.26.465975 ◽

2021 ◽

Author(s):

Meng Lin ◽

Pengfei Qiao ◽

Susanne Matschi ◽

Miguel Vasquez ◽

Guillaume P. Ramstein ◽

...

Keyword(s):

Candidate Genes ◽

Membrane Trafficking ◽

Genetic Architecture ◽

Natural Variation ◽

Crop Productivity ◽

Genomic Region ◽

Cell Wall Modification ◽

Major Barrier ◽

Maize Leaf ◽

Regulatory Variants

The cuticle, a hydrophobic layer of cutin and waxes synthesized by plant epidermal cells, is the major barrier to water loss when stomata are closed. Dissecting the genetic architecture of natural variation for maize leaf cuticular conductance (gc) is important for identifying genes relevant to improving crop productivity in drought-prone environments. To this end, we performed an integrated genome- and transcriptome-wide association study (GWAS/TWAS) to identify candidate genes putatively regulating variation in leaf gc. Of the 22 plausible candidate genes identified, five were predicted to be involved in cuticle precursor biosynthesis and export, two in cell wall modification, nine in intracellular membrane trafficking, and seven in the regulation of cuticle development. A gene encoding an INCREASED SALT TOLERANCE1-LIKE1 (ISTL1) protein putatively involved in intracellular protein and membrane trafficking was identified in GWAS and TWAS as the strongest candidate causal gene. A set of maize nested near-isogenic lines that harbor the ISTL1 genomic region from eight donor parents were evaluated for gc, confirming the association between gc and ISTL1 in a haplotype-based association analysis. The findings of this study provide novel insights into the role of regulatory variants in the development of the maize leaf cuticle, and will ultimately assist breeders to develop drought-tolerant maize for target environments.

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Genetic architecture of natural variation in cuticular hydrocarbon composition in Drosophila melanogaster

eLife ◽

10.7554/elife.09861 ◽

2015 ◽

Vol 4 ◽

Cited By ~ 61

Author(s):

Lauren M Dembeck ◽

Katalin Böröczky ◽

Wen Huang ◽

Coby Schal ◽

Robert R H Anholt ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Social Interactions ◽

Individual Variation ◽

Genetic Architecture ◽

Natural Variation ◽

Genetic Basis ◽

Acid Metabolism ◽

Cuticular Hydrocarbon ◽

Principal Component ◽

Hydrocarbon Composition

Insect cuticular hydrocarbons (CHCs) prevent desiccation and serve as chemical signals that mediate social interactions. Drosophila melanogaster CHCs have been studied extensively, but the genetic basis for individual variation in CHC composition is largely unknown. We quantified variation in CHC profiles in the D. melanogaster Genetic Reference Panel (DGRP) and identified novel CHCs. We used principal component (PC) analysis to extract PCs that explain the majority of CHC variation and identified polymorphisms in or near 305 and 173 genes in females and males, respectively, associated with variation in these PCs. In addition, 17 DGRP lines contain the functional Desat2 allele characteristic of African and Caribbean D. melanogaster females (more 5,9-C27:2 and less 7,11-C27:2, female sex pheromone isomers). Disruption of expression of 24 candidate genes affected CHC composition in at least one sex. These genes are associated with fatty acid metabolism and represent mechanistic targets for individual variation in CHC composition.

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Decision letter: Genetic architecture of natural variation in cuticular hydrocarbon composition in Drosophila melanogaster

10.7554/elife.09861.050 ◽

2015 ◽

Keyword(s):

Drosophila Melanogaster ◽

Genetic Architecture ◽

Natural Variation ◽

Cuticular Hydrocarbon ◽

Hydrocarbon Composition

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Unusual genetic architecture of natural variation affecting drug resistance in Drosophila melanogaster

Genetics Research ◽

10.1017/s0016672302005888 ◽

2002 ◽

Vol 80 (3) ◽

pp. 205-213 ◽

Cited By ~ 9

Author(s):

ROLAND CARRILLO ◽

GREG GIBSON

Keyword(s):

Drug Resistance ◽

Drosophila Melanogaster ◽

Genetic Variation ◽

Genetic Architecture ◽

Natural Variation ◽

Starvation Resistance ◽

Female Resistance ◽

Caffeine Ingestion ◽

Naturally Occurring ◽

Chronic Ingestion

Naturally occurring genetic variation was quantified for survival time of adult Drosophila melanogaster exposed to chronic ingestion of the drugs nicotine, caffeine, dopamine, tyramine and octopamine. Responses to nicotine, tyramine and octopamine were genetically correlated in both sexes, whereas caffeine response correlated with starvation resistance. However, there is also genetic variation that is specific for each of the drugs. Females tended to be more resistant than males to nicotine and caffeine but sex-by-genotype interactions were also seen for these drugs and for the response to dopamine. An unusual and complex genetic architecture was observed in crosses between lines with different responses to caffeine ingestion. Additive and dominance components were clearly seen from the analysis of F1 individuals, but increased female resistance to caffeine in backcross generations and increased male sensitivity in F2 generations confused the interpretation of possible epistatic contributions.

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Genetic Basis of Natural Variation in Spontaneous Grooming in Drosophila melanogaster

G3 Genes|Genome|Genetics ◽

10.1534/g3.120.401360 ◽

2020 ◽

Vol 10 (9) ◽

pp. 3453-3460

Author(s):

Aya Yanagawa ◽

Wen Huang ◽

Akihiko Yamamoto ◽

Ayako Wada-Katsumata ◽

Coby Schal ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Candidate Genes ◽

Natural Variation ◽

Genetic Basis ◽

Genetic Interaction ◽

Interaction Network ◽

Repetitive Behaviors ◽

Grooming Behavior ◽

Association Analyses ◽

Neuropsychiatric Diseases

Abstract Spontaneous grooming behavior is a component of insect fitness. We quantified spontaneous grooming behavior in 201 sequenced lines of the Drosophila melanogaster Genetic Reference Panel and observed significant genetic variation in spontaneous grooming, with broad-sense heritabilities of 0.25 and 0.24 in females and males, respectively. Although grooming behavior is highly correlated between males and females, we observed significant sex by genotype interactions, indicating that the genetic basis of spontaneous grooming is partially distinct in the two sexes. We performed genome-wide association analyses of grooming behavior, and mapped 107 molecular polymorphisms associated with spontaneous grooming behavior, of which 73 were in or near 70 genes and 34 were over 1 kilobase from the nearest gene. The candidate genes were associated with a wide variety of gene ontology terms, and several of the candidate genes were significantly enriched in a genetic interaction network. We performed functional assessments of 29 candidate genes using RNA interference, and found that 11 affected spontaneous grooming behavior. The genes associated with natural variation in Drosophila grooming are involved with glutamate metabolism (Gdh) and transport (Eaat); interact genetically with (CCKLR-17 D1) or are in the same gene family as (PGRP-LA) genes previously implicated in grooming behavior; are involved in the development of the nervous system and other tissues; or regulate the Notch and Epidermal growth factor receptor signaling pathways. Several DGRP lines exhibited extreme grooming behavior. Excessive grooming behavior can serve as a model for repetitive behaviors diagnostic of several human neuropsychiatric diseases.

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