Bacterial adaptation through loss of function.
Bacterial adaptation through loss of function.
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DOI：
10.1371/journal.pgen.1003617
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发表时间：
2013
期刊：
影响因子：
4.5
通讯作者：
Tavazoie S
中科院分区：
文献类型：
--
作者：
Hottes AK;Freddolino PL;Khare A;Donnell ZN;Liu JC;Tavazoie S
细菌的代谢能力和调节网络已经通过进化来优化，以响应每个物种的原生生态位中存在的选择压力。然而，在新的环境中，同样的细菌可能由于调控限制或生化缺陷而生长不良。对这些条件的适应可以通过由于功能突变的获得或通过细胞网络的调制而获得新的细胞功能来进行。通过对转座子诱变的细菌文库进行选择实验，我们表明，即使在极端营养限制的条件下，也可以通过丧失功能突变来实现实质性的适应，这些突变可以重新连接细胞的代谢，而不会获得酶或感觉功能。对100多种条件下类似实验的系统分析表明，在许多环境挑战下存在适应性功能突变损失。利用已发表文章中的大量例子，我们详细介绍了一系列机制，通过这些机制，功能丧失突变可以产生这种有益的调节变化，而不需要罕见的、特定的突变来微调酶活性或网络连接。功能丧失突变的高发生率表明，零突变在细菌群体适应新环境的早期阶段发挥了未被充分认识的作用。当细菌在其生存环境中遇到新的挑战时，例如抗生素治疗或营养来源不良，它们的种群面临着巨大的选择压力，为了在新的条件下更好地生长。我们通常认为细菌进化是根据获得的东西：例如，细菌可能获得抗生素抗性基因，或者修改现有的酶以更好地利用营养源。通过分析细菌种群在100多种不同条件下的适应性，我们表明，事实上，它们失去的东西可能同样重要：通过重新连接细胞的代谢，功能突变的丧失可以在许多具有挑战性的条件下提供大量的适应性益处，甚至在某些情况下，例如外来的营养组合，可能需要一些新的酶功能。由于可用的突变靶区更大，功能突变的丧失比特定功能的获得发生的频率要高得多。功能丧失突变的快速获取和广泛功能的结合表明，它们在细菌群体对新挑战的早期适应中发挥了重要作用。
The metabolic capabilities and regulatory networks of bacteria have been optimized by evolution in response to selective pressures present in each species' native ecological niche. In a new environment, however, the same bacteria may grow poorly due to regulatory constraints or biochemical deficiencies. Adaptation to such conditions can proceed through the acquisition of new cellular functionality due to gain of function mutations or via modulation of cellular networks. Using selection experiments on transposon-mutagenized libraries of bacteria, we illustrate that even under conditions of extreme nutrient limitation, substantial adaptation can be achieved solely through loss of function mutations, which rewire the metabolism of the cell without gain of enzymatic or sensory function. A systematic analysis of similar experiments under more than 100 conditions reveals that adaptive loss of function mutations exist for many environmental challenges. Drawing on a wealth of examples from published articles, we detail the range of mechanisms through which loss-of-function mutations can generate such beneficial regulatory changes, without the need for rare, specific mutations to fine-tune enzymatic activities or network connections. The high rate at which loss-of-function mutations occur suggests that null mutations play an underappreciated role in the early stages of adaption of bacterial populations to new environments. When bacteria encounter a new challenge in their environment, such as treatment with an antibiotic or a poor nutrient source, their population faces tremendous selective pressure to evolve in order to grow better under the new conditions. We typically think of bacterial evolution in terms of what is gained: a bacterium might, for example, acquire an antibiotic resistance gene, or modify an existing enzyme to make better use of a nutrient source. By analyzing the fitness of bacterial populations under more than 100 different conditions, we show that in fact what they lose can be equally important: by rewiring the cell's metabolism, loss of function mutations can provide substantial fitness benefits under many challenging conditions, even cases such as exotic nutrient combinations where some new enzymatic function might seem to be required. Loss of function mutations occur at a much higher frequency than gains of specific functionality due to the larger mutational target area available. The combination of the rapid acquisition and broad functionality of loss-of-function mutations suggests that they play a major role in the early adaptation of bacterial populations to new challenges.
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影响因子：
4.5
作者：
Girgis, Hany S.;Liu, Yirchung;Ryu, William S.;Tavazoie, Saeed
通讯作者：
Tavazoie, Saeed
影响因子：
14.8
作者：
Becker, Scott A.;Feist, Adam M.;Herrgard, Markus J.
通讯作者：
Herrgard, Markus J.
影响因子：
3.1
作者：
Boucher, JC;Mudd, HYMH;Deretic, V
通讯作者：
Deretic, V
影响因子：
64.5
作者：
Bollenbach T;Quan S;Chait R;Kishony R
通讯作者：
Kishony R
影响因子：
16
作者：
Goodarzi H;Elemento O;Tavazoie S
通讯作者：
Tavazoie S