Yeast as a model for understanding gene expression adaptation

描述（由申请人提供）：基因表达调控的变化在多大程度上推动了生命的进化创新是一个重要的未解决的问题。特别是，顺式监管的作用一直存在争议。虽然一些人认为顺式调节的变化是大多数形态适应的原因，但另一些人指出，只有少数这样的例子得到了证明。适应性调控差异（顺式或其他）的例子的缺乏可能在很大程度上是由于尚未开发出从基因组规模数据中识别此类案例的方法。我们最近开发了第一个这样的方法，它基于对任何一对菌株或物种之间调节差异的基因组规模目录的分析。我们已经证明了它能够检测基因，甚至是整个功能群/途径，这些功能群/途径受到基因表达变化的正选择的影响。现在最需要的是额外的数据来检测阳性选择的特征，以及精确定位和功能表征导致这些适应的单个核苷酸变化的方法。芽殖酵母是研究这些问题的理想模型。这项工作的最终结果，除了大大增加了对调控进化如何在分子水平上发生的理解之外，将是酵母顺式调控变化的全面目录，以及仅因单一适应性突变而不同的菌株（来自任何物种）的第一次收集。我们相信这些结果和资源将使酵母成为研究基因表达适应的主要模式生物。

DESCRIPTION (provided by applicant): To what extent changes in gene expression regulation drive the evolutionary innovations of life is an important unresolved question. In particular, the role of cis-regulation has been contentious. While some contend that changes in cis-regulation are responsible for the majority of morphological adaptations, others point out that only a few such cases have been demonstrated. The paucity of examples of adaptive regulatory divergence (cis-acting or otherwise) may be due in large part to the fact that no method for identifying such cases from genome-scale data has yet been developed. We have recently developed the first such method, which is based on analysis of genome-scale catalogs of regulatory differences between any pair of strains or species. We have demonstrated its ability to detect genes and even entire functional groups/pathways that have been subject to positive selection for changes in gene expression. What is now most needed is additional data from which to detect the signature of positive selection, as well as methods to pinpoint and functionally characterize the individual nucleotide changes responsible for these adaptations. Saccharomyces budding yeast represents an ideal model in which to study these questions. The end result of this work, in addition to a greatly increased understanding of how regulatory evolution occurs at the molecular level, will be a comprehensive catalog of cis-regulatory changes in yeast, as well as the first collection of strains (from any species) differing only by single adaptive mutations. We believe that this collection of results and resources will transform yeast into the leading model organism for studying gene expression adaptation.