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

• 批准号: 7220829
• 负责人: SASHA F LEVY
• 金额: $ 4.68万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/7220829
• 关键词: Identification; phenotypic; capacitors; environmental; genotypic

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：项目总结：表型电容器缓冲发育表型对基因型或环境变异的影响。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，电容器可能会失败，从而在表型上揭示变异。这种活动提供了一种机制，通过这种机制，隐藏的多态性可以积累，并通过表型电容器的故障，一种机制，通过这种机制，可以促进进化的变化。表型电容器的主要例子是Hsp 90，一种分子伴侣，通常抑制表型变异，但在功能受损时释放这种变异，导致多效性表型效应。虽然只有热休克蛋白90已被证明是作为一个表型电容器的基因型和环境变化，一些实验和计算研究表明，热休克蛋白90可能不是唯一的在这个角色。在这项研究中，我将测试的假设，多个基因产物能够作为环境和基因型变异的表型电容器。在初步结果中，我分析了现有的定量形态学数据从4718酿酒酵母单基因缺失菌株的高整体表型变异，并确定了多个假定的电容器的环境变化。目标1。为了检验能够充当环境变异的表型电容器的基因产物也充当基因型变异的电容器的假设，将在编码推定的环境电容器的基因中具有缺失的实验室酵母菌株与野生分离菌株杂交以产生遗传变异。将使用一系列定量表型测定比较含缺失和野生型F1单倍体分离体的表型变异性。目标2.为了鉴定可能充当表型电容器的数量性状基因座，将对遗传上不同的实验室菌株和野生分离株之间的杂交的现有基因分型品系进行高和低表型方差的连锁分析。新型表型电容器的鉴定和表征将增强对表型稳健性、癌细胞进展以及包括微生物病原体在内的生物体进化变化机制的理解。 相关性：我计划确定影响进化变化速度的关键基因。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，癌细胞经历了从正常细胞到恶性细胞的进化形式。因此，这里确定的基因可能对理解癌症如何发展和治疗很重要。