FUNCTIONAL MAP OF THE YEAST GENOME

1996年4月酵母基因组序列的完成开启了全基因组基因功能探索的时代。该项目的目标是制作一张详细的酵母菌基因组“功能图”。许多功能属性可以自然地映射到基因组序列提供的框架上。首要目标是将任何可能有助于理解基因组和了解基因组序列中的静态信息如何在活着的有机体中产生生命的信息映射到这个框架上。大多数拟议的工作依赖于该实验室几年前开发的DNA微阵列技术，该技术为在全基因组基础上研究基因和DNA序列的各种性质提供了一种方便、通用和经济的工具。设想了三个主要项目：1.全球基因表达计划的全面调查。将确定数千种条件对每个酵母基因表达的影响，包括不同的环境和遗传扰动以及内源遗传程序。将进行一项系统的调查，旨在确定酵母基因组中每个假定的调控基因所调控的目标基因。已经在开发中的计算工具将被用于从每个基因的表达模式中推断功能，并识别解释所观察到的表达模式的候选顺式调控元件。2.将绘制蛋白质与酵母基因组结合的体内模式的详细图谱。3.将开发一种基于微阵列的新方法，用于在基因组范围内分析显性突变的后果。这一程序最初将用于确定在不同的选择条件下，每个酵母基因的过度表达对适合度的影响。在整个工作过程中，我们将继续努力发明和发现使用DNA微阵列技术和其他实验方法来探索基因组的新方法。

The completion of the yeast genome sequence in April 1996 inaugurated the era of genome-wide exploration of gene function. The goal of this project is to produce a detailed "functional map" of the yeast genome. A great many functional attributes can naturally be mapped onto the framework that the genome sequence provides. The overarching goal is to map onto this framework any kind of information that might be useful in understanding the genome, and understanding how the static information in the genome sequence comes to life in the living organism. Most of the proposed work relies on the DNA microarray technology that was developed in this laboratory a few years ago, which provides a convenient, versatile and economical tool for investigating diverse properties of genes and DNA sequences on a genome-wide basis. Three principal projects are envisioned: 1. A comprehensive survey of global gene expression programs. The effects on expression of every yeast gene of thousands of conditions, including diverse environmental and genetic perturbations as well as endogenous genetic programs, will be determined. A systematic survey will be conducted, aimed at identifying the target genes regulated by each putative regulatory gene in the yeast genome. Computational tools, already under development, will be used to draw inferences of function from the patterns of expression of each gene, and to identify candidate cis-regulatory elements that account for the observed expression patterns. 2. A detailed map of the in vivo pattern of protein binding to the yeast genome will be developed. 3. A new microarray-based method for analyzing the consequences of dominant mutations on a genomic scale will be developed. This procedure will be applied initially to define the consequences of overexpression of each yeast gene on fitness under a diverse set of selective conditions. Throughout the course of this work, we will continue our ongoing efforts to invent and discover new ways to use DNA microarray technology and other experimental approaches to explore the genome.