1 Natural Genetic Variation in a Dopamine Receptor is Associated With Variation in Female Fertility in Drosophila melanogaster

Abstract

Fertility is a major component of fitness but its genetic architecture remains poorly understood. Using a full diallel cross of 50 Drosophila melanogaster Genetic Reference Panel inbred lines with full genome sequences, we found substantial genetic variation in fertility largely attributable to females. We mapped genes associated with variation in female fertility by genome-wide association analysis of common variants in the fly genome. Validation of candidate genes by RNAi knockdown confirmed the role of the dopamine 2-like receptor (Dop2R) in promoting egg laying. We replicated the Dop2R effect in an independently collected productivity dataset and showed that the effect of the Dop2R variant was mediated in part by regulatory gene expression variation. This study demonstrates the strong potential of genome-wide association analysis in this diverse panel of inbred strains and subsequent functional analyses for understanding the genetic architecture of fitness traits. Author SummaryIn evolutionary genetics, fitness is defined as the number of offspring an individual contributes to the next generation. This is determined by an individuals viability (its ability to survive past the reproductive age) and its fertility. Although understanding the genetic basis for natural variation in fitness is a major goal of evolutionary and population genetics, the genetic factors that contribute to variation in fertility in natural populations have remained largely unresolved. To address this issue, we took advantage of the Drosophila Genetic Reference Panel, a population of inbred, sequenced fly lines derived from a natural population. In this panel, there is minimal genetic variation among individuals within each line, whereas variation among the lines reflects the variation observed in the original population from which they were derived. We generated all possible pairwise crosses among 50 of these lines (2,500 distinct genotypes) and measured the productivity (number of offspring produced) for each genotype. We found considerable natural variation in productivity that was primarily determined by the female genotype. We performed a genome wide association as analysis and identified and functionally validated a dopamine receptor that plays a major role in determining variation in female fertility through an effect on egg-laying.