Natural genetic variation in a dopamine receptor is associated with variation in female fertility in Drosophila melanogaster
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Abstract
Fertility is a major component of fitness but its genetic architecture remains poorly understood. Using a full diallel cross of 50 Drosophila Genetic Reference Panel inbred lines with whole 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.
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herefore, we hypothesize that the association of Dop2R with variation in female productivity in the DGRP may at least partially arise from naturally occurring variation in expression of Dop2R in DGRP females, which then causes variation in the amount of DA that regulates fertility via changes in JH and 20E titers. Dop2R expression is genetically variable in the DGRP, with a broad sense heritability in females ∼ 0.70 [16]. We found a strong correlation between Dop2R expression in females with productivity (r = 0.34, P = 9.81e-7, Figure 4b) but a relatively weak effect of the Dop2R SNP on expression (P = 0.09). Mediation analysis revealed that approximately 19% (P = 0.09) of the effect of the Dop2R SNP on productivity was mediated by the effect of Dop2R expression.
I believe there is a *Dop2R *mutant available. Have you looked at these …
herefore, we hypothesize that the association of Dop2R with variation in female productivity in the DGRP may at least partially arise from naturally occurring variation in expression of Dop2R in DGRP females, which then causes variation in the amount of DA that regulates fertility via changes in JH and 20E titers. Dop2R expression is genetically variable in the DGRP, with a broad sense heritability in females ∼ 0.70 [16]. We found a strong correlation between Dop2R expression in females with productivity (r = 0.34, P = 9.81e-7, Figure 4b) but a relatively weak effect of the Dop2R SNP on expression (P = 0.09). Mediation analysis revealed that approximately 19% (P = 0.09) of the effect of the Dop2R SNP on productivity was mediated by the effect of Dop2R expression.
I believe there is a *Dop2R *mutant available. Have you looked at these animals? they might prove useful in testing some mechanistic hypotheses.
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The most significant SNP (P = 3.42 × 10−7) is 1,612 bp downstream of the gene encoding the dopamine 2-like receptor (Dop2R), and explained approximately 47% of the genetic variance of productivity in females.
Wow! This is an amazing result!
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Therefore, we adjusted productivity for the Wolbachia infection status of parents before further analyses.
Did you examine whether there was an interaction between Wolbachia infection and any of the alleles you mapped?
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