Yeast as a model for understanding gene expression adaptation

描述(申请人提供)：基因表达调控的变化在多大程度上推动生命的进化创新是一个重要的悬而未决的问题。特别是，顺势监管的作用一直存在争议。虽然一些人认为顺式调控的变化是大多数形态适应的原因，但另一些人指出，只有少数这样的情况被证明。适应性调节分化(顺式作用或其他作用)的例子很少，这在很大程度上可能是因为还没有开发出从基因组规模的数据中识别这种情况的方法。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的调控差异的基因组规模目录的分析。我们已经证明了它有能力检测基因，甚至整个功能基团/通路，这些基因表达的变化受到了正向选择的影响。现在最需要的是检测正选择特征的额外数据，以及确定导致这些适应的单个核苷酸变化并在功能上确定其特征的方法。发芽酵母是研究这些问题的理想模型。这项工作的最终结果，除了大大提高对调控进化如何在分子水平上发生的理解外，还将是酵母中顺式调控变化的全面目录，以及第一批只有单一适应突变不同的菌株(来自任何物种)。我们相信，这些结果和资源的集合将把酵母转变为研究基因表达适应的领先模式生物。

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.