A new system for comparative functional genomics of Saccharomyces yeasts.

A new system for comparative functional genomics of Saccharomyces yeasts.
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DOI:
10.1534/genetics.113.152918
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发表时间:
2013-09
期刊:
影响因子:
3.3
通讯作者:
Dunham MJ
Dunham MJ
中科院分区:
生物学2区
文献类型:
--
作者:
Caudy AA;Guan Y;Jia Y;Hansen C;DeSevo C;Hayes AP;Agee J;Alvarez-Dominguez JR;Arellano H;Barrett D;Bauerle C;Bisaria N;Bradley PH;Breunig JS;Bush E;Cappel D;Capra E;Chen W;Clore J;Combs PA;Doucette C;Demuren O;Fellowes P;Freeman S;Frenkel E;Gadala-Maria D;Gawande R;Glass D;Grossberg S;Gupta A;Hammonds-Odie L;Hoisos A;Hsi J;Hsu YH;Inukai S;Karczewski KJ;Ke X;Kojima M;Leachman S;Lieber D;Liebowitz A;Liu J;Liu Y;Martin T;Mena J;Mendoza R;Myhrvold C;Millian C;Pfau S;Raj S;Rich M;Rokicki J;Rounds W;Salazar M;Salesi M;Sharma R;Silverman S;Singer C;Sinha S;Staller M;Stern P;Tang H;Weeks S;Weidmann M;Wolf A;Young C;Yuan J;Crutchfield C;McClean M;Murphy CT;Llinás M;Botstein D;Troyanskaya OG;Dunham MJ

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全基因组测序,特别是真菌的全基因组测序,已经取得了巨大的进步。然而,更困难的是对仅从比较序列分析中得出的基因功能推论进行实验测试。我们提出了一种已测序但实验尚未充分研究的芽殖酵母 Saccharomyces bayanus var. 的全基因组功能特征。 uvarum(以下称为 S. bayanus),使我们能够绘制出该生物体与酿酒酵母在 2000 万年中的变化图。我们首先创建了一套遗传工具来促进 S. bayanus 的工作。接下来,我们测量了 S. bayanus 对一组不同扰动的基因表达响应,这些扰动使用计算方法进行了优化,以涵盖多种功能相关的生物反应。由此产生的数据集表明,基因表达模式在很大程度上是保守的,但碳水化合物利用和减数分裂等调控网络可能存在显着变化。除了监管变化之外,我们的方法还发现了基因功能的差异。核心通路中基因的功能高度保守,但我们观察到许多参与渗透应激、过氧化物酶体生物合成和自噬的基因的变化。数量惊人的贝酵母特异基因对氧化应激作出反应,表明该生物体可能在与酿酒酵母不同的选择压力下进化。这项工作将基因组规模进化研究的范围从基于序列的分析扩展到快速实验表征,并且可用于任何感兴趣的谱系的功能作图。此外,我们对 S. bayanus 的详细表征为酵母的比较功能基因组学研究提供了宝贵的资源。
Whole-genome sequencing, particularly in fungi, has progressed at a tremendous rate. More difficult, however, is experimental testing of the inferences about gene function that can be drawn from comparative sequence analysis alone. We present a genome-wide functional characterization of a sequenced but experimentally understudied budding yeast, Saccharomyces bayanus var. uvarum (henceforth referred to as S. bayanus), allowing us to map changes over the 20 million years that separate this organism from S. cerevisiae. We first created a suite of genetic tools to facilitate work in S. bayanus. Next, we measured the gene-expression response of S. bayanus to a diverse set of perturbations optimized using a computational approach to cover a diverse array of functionally relevant biological responses. The resulting data set reveals that gene-expression patterns are largely conserved, but significant changes may exist in regulatory networks such as carbohydrate utilization and meiosis. In addition to regulatory changes, our approach identified gene functions that have diverged. The functions of genes in core pathways are highly conserved, but we observed many changes in which genes are involved in osmotic stress, peroxisome biogenesis, and autophagy. A surprising number of genes specific to S. bayanus respond to oxidative stress, suggesting the organism may have evolved under different selection pressures than S. cerevisiae. This work expands the scope of genome-scale evolutionary studies from sequence-based analysis to rapid experimental characterization and could be adopted for functional mapping in any lineage of interest. Furthermore, our detailed characterization of S. bayanus provides a valuable resource for comparative functional genomics studies in yeast.
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