Evidence that Egfr contributes to cryptic genetic variation for photoreceptor determination in natural populations of Drosophila melanogaster
Evidence that Egfr contributes to cryptic genetic variation for photoreceptor determination in natural populations of Drosophila melanogaster
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DOI：
10.1016/j.cub.2003.10.001
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发表时间：
2003-10-28
期刊：
影响因子：
9.2
通讯作者：
Gibson, G
中科院分区：
文献类型：
--
作者：
Dworkin, I;Palsson, A;Gibson, G
定量遗传学的一个目标是确定基因内的核苷酸变异，这些变异有助于表型变异和易感性。在进化的背景下，这意味着表征分子多态性，改变外显率和表达性的扰动性状。一项对近11kb黑腹龙Egfr中267个snp与210个等基因野生型系中Egfr（E1）等位基因获得的眼睛粗化程度之间的关联的调查提供了少量同义替换为光感受器决定提供了隐变的证据。在两组不同Egfr（E1）背景的杂交中，有10个位点超过Bonferroni阈值，其中包括编码区3'端紧密连锁不平衡的一个特别重要的位点群。该簇与另一个位点的上位性相互作用增强了该单倍型的表达性。利用改进的病例对照和传播不平衡试验，从1000个Egfr（E1）杂交中获得的302个表型极端个体的独立样本与新捕获的雄性之间的最强关联得到了复制。罕见的等位基因更容易破坏眼睛发育，这表明突变选择平衡可能是维持Egfr隐型变异的一种机制。
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 Egfr(E1) 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 Egfr(E1) backgrounds including a particularly significant cluster of sites in tight linkage disequilibriurn 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 Egfr(E1) 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.