Evidence that Egfr Contributes to Cryptic Genetic Variation for Photoreceptor Determination in Natural Populations of Drosophila melanogaster

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Abstract

One objective of quantitative genetics is to identify the nucleotide variants within genes that contribute to phenotypic variation and susceptibility [1]. In an evolutionary context, this means characterizing the molecular polymorphisms that modify the penetrance and expressivity of perturbed traits. A survey of association between 267 SNPs in almost 11 kb of the D. melanogaster Egfr and the degree of eye roughening due to a gain-of-function EgfrE1 allele crossed into 210 isogenic wild-type lines provides evidence that a handful of synonymous substitutions supply cryptic variation for photoreceptor determination. Ten sites exceed Bonferroni threshold for association in two sets of crosses to different EgfrE1 backgrounds including a particularly significant cluster of sites in tight linkage disequilibrium toward the 3′ end of the coding region. Epistatic interaction of this cluster with one other site enhances the expressivity of this haplotype. Replication of the strongest associations with an independent sample of 302 phenotypically extreme individuals derived from 1000 crosses of EgfrE1 to freshly trapped males was achieved using modified case-control and transmission-disequilibrium tests. A tendency for the rarer alleles to have more disrupted eye development suggests that mutation-selection balance is a possible mechanism contributing to maintaining cryptic variation for Egfr.

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Dworkin, I., Palsson, A., Birdsall, K., & Gibson, G. (2003). Evidence that Egfr Contributes to Cryptic Genetic Variation for Photoreceptor Determination in Natural Populations of Drosophila melanogaster. Current Biology, 13(21), 1888–1893. https://doi.org/10.1016/j.cub.2003.10.001

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