Metabolic functions of duplicate genes in Saccharomyces cerevisiae
Metabolic functions of duplicate genes in Saccharomyces cerevisiae
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DOI：
10.1101/gr.3992505
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发表时间：
2005-10-01
期刊：
影响因子：
7
通讯作者：
Blank, LM
中科院分区：
文献类型：
--
作者：
Kuepfer, L;Sauer, U;Blank, LM
重复基因的作用及其对酶可分配性现象的贡献是分子和基因组进化中的一个中心问题。然而，目前还缺乏对可能导致其保存的机制的全面分类。在系统生物学方法中，我们对酿酒酵母代谢的105个重复基因家族的Back-Lip、调节和基因剂量功能进行了分类。关键工具是协调的基因组规模代谢模型iLL672，该模型基于较旧的iFF708。所有代谢基因敲除的计算预测与实验确定的整个46S8突变体单态酵母文库在五个环境条件下的表型进行了验证。ILL672分别正确识别了96%-98%和73%-80%的存活和致死单胞体表型。通过整合在电子重复基因敲除表型中预测的iLL672、基因组规模的碳流分布、单态突变表型和网络拓扑分析来确定每个重复家族的功能角色。这些结果没有提供证据证明基因组中存在维持重复基因的特定显性功能。特别是，Back-Lip功能并不受进化选择的青睐，因为在必要的反应中，重复基因并不比单一基因更频繁地出现。多基因编码的酶涵盖不同的功能，而不是占主导地位的作用。因此，至少对于新陈代谢来说，基因组中副对数部分的持久性可以用一系列不同的、经常重叠的功能角色来更好地解释。
The roles of duplicate genes and their contribution to the phenomenon of enzyme dispensability are a central issue in molecular and genome evolution. A comprehensive classification of the mechanisms that may have led to their preservation, however, is currently lacking. In a systems biology approach, we classify here back-Lip, regulatory, and gene dosage functions for the 105 duplicate gene families of Saccharomyces cerevisiae metabolism. The key tool was the reconciled genome-scale metabolic model iLL672, which was based oil the older iFF708. Computational predictions of all metabolic gene knockouts were validated with the experimentally determined phenotypes of the entire singleton yeast library of 46S8 Mutants under five environmental conditions. iLL672 correctly identified 96%-98% and 73%-80% of the viable and lethal singleton phenotypes, respectively. Functional roles for each duplicate family were identified by integrating the iLL672-predicted in silico duplicate knockout phenotypes, genome-scale carbon-flux distributions, singleton Mutant phenotypes, and network topology analysis. The results provide no evidence for a particular dominant function that maintains duplicate genes in the genome. In particular, the back-Lip function is not favored by evolutionary selection because duplicates do not Occur more frequently in essential reactions than singleton genes. Instead of a prevailing role, multigene-encoded enzymes cover different functions. Thus, at least for metabolism, persistence of the paralog fraction in the genome can be better explained with ail array of different, often overlapping functional roles.