Variation in mean food intake in the DGRP.

<p>(<b>A</b>) Mean food intake in 182 DGRP lines, arranged in order from lowest to highest in females (red diamonds). Mean food intake of males (blue squares) are given in the same order as the female scores. (<b>B</b>) Sexual dimorphism of food intake. The female-male difference in mean food intake of each line is ordered from lowest to highest. All error bars are ± SE.</p

SNP-based functional validation.

<p><b>(A)</b> Mating scheme for generating outbred lines homozygous for major and minor SNP alleles. Two parental genotypes homozygous for the focal highlighted SNP and the tested F₁ genotype are depicted. <b>(B)</b><i>3R</i>_13637022_SNP validation results for females (red bars) and males (blue bars) (± SE). *: <i>P</i> = 0.029.</p

Variation in <i>CV</i>_<i>E</i> of food intake in the DGRP.

<p>(<b>A</b>) <i>CV</i>_<i>E</i> of food intake, arranged in order from lowest to highest in females (red diamonds). <i>CV</i>_<i>E</i> of food intake of males (blue squares) are given in the same order as the females. (<b>B</b>) Association of mean and <i>CV</i>_<i>E</i> for food intake for females (red diamonds) and males (blue squares).</p

Analyses of variance (ANOVA) of food intake.

<p>df: degrees of freedom; MS: type III mean squares; F: F-statistic; <i>σ</i>² variance component estimated using restricted maximum likelihood.</p><p>Analyses of variance (ANOVA) of food intake.</p

RNAi functional validation.

<p>Effects of RNAi knock down on (<b>A</b>) mean food intake and (<b>B</b>) within-genotype variance of food intake of females (red bars) and males (blue bars) for 31 candidate genes. All values are deviations from the control. Error bars are ± SE. *: <i>P</i> < 0.05; **: <i>P</i> < 0.01; ***: <i>P</i> < 0.0001.</p

Quantitative Genetics of Food Intake in <i>Drosophila melanogaster</i>

<div><p>Food intake is an essential animal activity, regulated by neural circuits that motivate food localization, evaluate nutritional content and acceptance or rejection responses through the gustatory system, and regulate neuroendocrine feedback loops that maintain energy homeostasis. Excess food consumption in people is associated with obesity and metabolic and cardiovascular disorders. However, little is known about the genetic basis of natural variation in food consumption. To gain insights in evolutionarily conserved genetic principles that regulate food intake, we took advantage of a model system, <i>Drosophila melanogaster</i>, in which food intake, environmental conditions and genetic background can be controlled precisely. We quantified variation in food intake among 182 inbred, sequenced lines of the <i>Drosophila melanogaster</i> Genetic Reference Panel (DGRP). We found significant genetic variation in the mean and within-line environmental variance of food consumption and observed sexual dimorphism and genetic variation in sexual dimorphism for both food intake traits (mean and variance). We performed genome wide association (GWA) analyses for mean food intake and environmental variance of food intake (using the coefficient of environmental variation, <i>CV</i>_<i>E</i>, as the metric for environmental variance) and identified molecular polymorphisms associated with both traits. Validation experiments using RNAi-knockdown confirmed 24 of 31 (77%) candidate genes affecting food intake and/or variance of food intake, and a test cross between selected DGRP lines confirmed a SNP affecting mean food intake identified in the GWA analysis. The majority of the validated candidate genes were novel with respect to feeding behavior, and many had mammalian orthologs implicated in metabolic diseases.</p></div

Brown-Forsythe and Levene’s tests for unequal variance.

<p>df: degrees of freedom; F: F statistic.</p><p>Brown-Forsythe and Levene’s tests for unequal variance.</p