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Identification of phenotypic capacitors of environmental and genotypic variation

环境和基因型变异的表型电容器的鉴定

基本信息

批准号：
7544919
负责人：
SASHA F LEVY
金额：
$ 5.17万
依托单位：
NEW YORK UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-01-17 至 2010-01-16
项目状态：
已结题

项目摘要

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.

项目总结：表型电容器缓冲发育表型对基因型或环境变化在正常条件下，这种缓冲导致稳健的表型;然而，当受到恶劣环境或突变的挑战时，电容器可能会失效，从而显示出变化。表型上此活动提供了一种机制，通过该机制，隐藏的多态性可以累积以及通过表型电容器的失效，可以促进进化变化的机制。表型电容器的主要例子是Hsp 90，它是一种分子伴侣，表型变异，但在功能受损时释放这种变异，导致多效性。表型效应虽然只有Hsp 90被证明是两种基因型的表型电容器，和环境变化，一些实验和计算研究表明，Hsp 90可能不是在这个角色中独一无二。在这项研究中，我将测试的假设，多个基因产物能够发挥作用，作为环境和基因型变异的表型电容器。在初步结果中，分析了现有的4718个酿酒酵母单基因的定量形态学数据缺失菌株的高整体表型变异，并确定了多个推定的电容器，环境变化目标1。为了验证基因产物能够作为表型环境变化的电容器也充当基因型变化的电容器，编码推定的环境电容器的基因中的缺失将与野生分离菌株杂交，产生遗传变异。含缺失和野生型F1单倍体的表型变异将使用一系列定量表型测定来比较分离子。目标二。以识别数量性状基因座可能作为表型电容器，连锁分析高，低表型将对遗传上不同的实验室菌株之间杂交的现有基因型品系进行方差分析野生隔离。新型表型电容器的鉴定和表征将增强了解表型的稳健性，癌细胞的进展，以及进化的机制，包括微生物病原体在内的生物体的变化。相关性：我计划确定影响免疫系统的关键基因。进化变化的速度。许多人类病原体迅速进化，以避免免疫反应或抗生素这项研究将有助于了解这种进化背后的机制和基因。此外，本发明还癌细胞经历了从正常细胞到恶性细胞的进化形式。因此，基因在这里确定的可能是重要的了解癌症的进展和可能的治疗。