Identification of phenotypic capacitors of environmental and genotypic variation

项目摘要：表型电容器可缓冲发育表型以对抗基因或 环境变化。在正常情况下，这种缓冲会产生健壮的表型；然而， 当受到恶劣环境或突变的挑战时，电容器可能会失效，从而揭示出变化 典型的。此活动提供了一种机制，通过该机制可以积累隐藏的多态 而且，通过表型电容器的故障，可以促进进化变化的机制。 表型电容器的主要例子是Hsp90，一种分子伴侣，通常会抑制 表型变异，但当功能受损时会释放这种变异，导致多效性 表型效应。虽然只有Hsp90被证明是这两种基因的表型电容器 和环境变异，一些实验和计算研究表明，Hsp90可能不会 在这个角色中是独一无二的。在这项研究中，我将检验多个基因产物能够起作用的假设 作为环境和基因变异的表型电容器。在初步结果中，我有 4718株酿酒酵母单基因已有定量形态数据分析 总表型变异较大的缺失菌株，并鉴定出多个可能的电容器 环境变化。目的1.检验基因产物能够作为表型的假设 环境变化的电容器也是基因变异的电容器，具有 编码可能的环境电容器的基因的缺失将与一种野生分离株杂交，以 产生遗传变异。含缺失型和野生型F1单倍体的表型变异 分离者将使用一系列定量表型分析进行比较。目标2.确定 可作为表型电容的数量性状基因座，高表型和低表型的连锁分析 将对遗传上不同的实验室菌株之间的杂交的现有基因分型系进行变异 和野生的隔离。新型表型电容器的鉴定和表征将增强 对表型稳定性、癌细胞进展和进化机制的理解 包括微生物病原体在内的生物体的变化。相关性：我计划找出影响 进化变化的速度。许多人类病原体进化迅速，以避免免疫反应或 抗生素。这项研究将有助于理解这种进化背后的机制和基因。另外， 癌细胞经历了从正常细胞到恶性细胞的进化过程。因此，基因 这里发现的可能对了解癌症的进展和可能的治疗很重要。

Project Summary: A phenotypic capacitor buffers the developmental phenotype against genotypic or environmental variation. Under normal conditions, this buffering results in a robust phenotype; however, when challenged by a harsh environment or mutation, the capacitor may fail, thereby revealing the variation phenotypically. This activity provides for both a mechanism by which hidden polymorphism can accumulate and, by failure of the phenotypic capacitor, a mechanism by which evolutionary change can be promoted. The primary example of a phenotypic capacitor is Hsp90, a molecular chaperone that normally suppresses phenotypic variation but releases this variation when functionally compromised, resulting in pleiotropic phenotypic effects. While only Hsp90 has been shown to act as a phenotypic capacitor of both genotypic and environmental variation, several experimental and computational studies suggest Hsp90 may not be unique in this role. In this study, I will test the hypothesis that multiple gene products are capable of acting as phenotypic capacitors of environmental and genotypic variation. In the preliminary results, I have analyzed existing quantitative morphological data from 4718 Saccharomyces cerevisiae single-gene deletion strains for high overall phenotypic variance and identified multiple putative capacitors of environmental variation. Aim 1. To test the hypothesis that gene products capable of acting as phenotypic capacitors of environmental variation also act as capacitors of genotypic variation, lab yeast strains with deletions in genes that code for putative environmental capacitors will be crossed with a wild isolate strain to generate genetic variation. The phenotypic variability of deletion-containing and wild-type F1 haploid segregants will be compared using an array of quantitative phenotypic assays. Aim 2. To identify quantitative trait loci that may act as phenotypic capacitors, linkage analysis for high and low phenotypic variance will be performed on existing genotyped lines of a cross between a genetically divergent lab strain and wild isolate. The identification and characterization of novel phenotypic capacitors will enhance the understanding of phenotypic robustness, cancer cell progression, and the mechanisms for evolutionary change of organisms including microbial pathogens. Relevance: I plan to identify key genes that affect the rate of evolutionary change. Many human pathogens evolve rapidly to avoid the immune response or antibiotics. This study will help understand the mechanisms and genes behind this evolution. Additionally, cancer cells go through a form of evolution from being normal cells to becoming malignant. Thus, genes identified here are likely to be important to understanding how cancer progresses and may be treated.