Multicopy suppression underpins metabolic evolvability
Multicopy suppression underpins metabolic evolvability
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DOI：
10.1093/molbev/msm204
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发表时间：
2007-12-01
影响因子：
10.7
通讯作者：
Matsumura, Ichiro
中科院分区：
文献类型：
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作者：
Patrick, Wayne M.;Quandt, Erik M.;Matsumura, Ichiro
我们对新代谢功能起源的理解是基于遗传和生物化学证据。一些营养缺陷型可以通过过表达底物不明确的酶（即，在不同底物上催化相同化学转化的那些）。其他酶在体外表现出弱但可检测的催化混杂性（即，它们在相似的底物上催化不同的转化）。细胞通过这些次级活动的进化来适应新的环境，但它们的化学性质和发生频率都没有被整体表征。在这里，我们系统地确定了大肠杆菌基因组中的多功能基因。我们筛选了104个单基因敲除菌株，发现这些营养缺陷型中的许多（20%）被至少一个非同源E. coli基因。被删除的基因和它的抑制基因通常是无关的，这表明滥交是偶然性的产物。这项全基因组调查表明，多功能基因是常见的，并说明了其产品增强代谢的鲁棒性和进化的机制多样性。
Our understanding of the origins of new metabolic functions is based upon anecdotal genetic and biochemical evidence. Some auxotrophies can be suppressed by overexpressing substrate-ambiguous enzymes (i.e., those that catalyze the same chemical transformation on different substrates). Other enzymes exhibit weak but detectable catalytic promiscuity in vitro (i.e., they catalyze different transformations on similar substrates). Cells adapt to novel environments through the evolution of these secondary activities, but neither their chemical natures nor their frequencies of occurrence have been characterized en bloc. Here, we systematically identified multifunctional genes within the Escherichia coli genome. We screened 104 single-gene knockout strains and discovered that many (20%) of these auxotrophs were rescued by the overexpression of at least one noncognate E. coli gene. The deleted gene and its suppressor were generally unrelated, suggesting that promiscuity is a product of contingency. This genome-wide survey demonstrates that multifunctional genes are common and illustrates the mechanistic diversity by which their products enhance metabolic robustness and evolvability.