Divergence of iron metabolism in wild Malaysian yeast.
Divergence of iron metabolism in wild Malaysian yeast.
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DOI：
10.1534/g3.113.008011
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发表时间：
2013-12-09
期刊：
影响因子：
--
通讯作者：
Brem RB
中科院分区：
文献类型：
--
作者：
Lee HN;Mostovoy Y;Hsu TY;Chang AH;Brem RB
比较基因组学研究报告了物种内和物种间基因表达水平的广泛差异。使用这些数据来推断生物体水平的特征差异已被证明是该领域的一个关键挑战。我们使用马来西亚野生酿酒酵母种群作为试验床，根据对调控变异的观察来预测和验证性状差异。马来西亚酵母在标准培养基中培养时，会激活调节程序，保护细胞免受高铁的毒性影响。马来西亚酵母在过量铁存在的培养过程中也表现出过度活跃的调节反应，并且在高铁条件下具有独特的生长缺陷。分子验证实验确定了铁代谢因子AFT1、CCC1和YAP5是这些分子和细胞表型的贡献者；在基因组规模的序列分析中，一套铁毒反应基因显示了马来西亚酵母中蛋白质的快速进化。我们的发现支持这样一个模型，即由于选择压力的变化，马来西亚酵母中的铁代谢发生了变化，马来西亚等位基因将铁反应的动态范围转移到低铁浓度，并削弱了对极端铁毒的抵抗力。通过剖析马来西亚酵母的缺铁专家行为，我们的工作突出了表达差异的力量，它是生物和进化水平上相关变异的标志。解释基因表达变异的表型相关性是现代基因组学的主要挑战之一。
Comparative genomic studies have reported widespread variation in levels of gene expression within and between species. Using these data to infer organism-level trait divergence has proven to be a key challenge in the field. We have used a wild Malaysian population of S. cerevisiae as a test bed in the search to predict and validate trait differences based on observations of regulatory variation. Malaysian yeast, when cultured in standard medium, activated regulatory programs that protect cells from the toxic effects of high iron. Malaysian yeast also showed a hyperactive regulatory response during culture in the presence of excess iron and had a unique growth defect in conditions of high iron. Molecular validation experiments pinpointed the iron metabolism factors AFT1, CCC1, and YAP5 as contributors to these molecular and cellular phenotypes; in genome-scale sequence analyses, a suite of iron toxicity response genes showed evidence for rapid protein evolution in Malaysian yeast. Our findings support a model in which iron metabolism has diverged in Malaysian yeast as a consequence of a change in selective pressure, with Malaysian alleles shifting the dynamic range of iron response to low-iron concentrations and weakening resistance to extreme iron toxicity. By dissecting the iron scarcity specialist behavior of Malaysian yeast, our work highlights the power of expression divergence as a signpost for biologically and evolutionarily relevant variation at the organismal level. Interpreting the phenotypic relevance of gene expression variation is one of the primary challenges of modern genomics.
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