Mutational hotspots lead to robust but suboptimal adaptive outcomes in certain environments
Mutational hotspots lead to robust but suboptimal adaptive outcomes in certain environments
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突变热点在某些环境中会导致稳健但次优的适应性结果
DOI：
10.1101/2023.06.07.543998
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Flanagan L
中科院分区：
文献类型：
--
作者：
Flanagan L
观察到的适应性结果的突变谱可能受到许多因素的限制。例如，突变偏差可以通过增加基因组中孤立位点的突变率来缩小观察范围。相反，复杂的环境可以通过定义突变途径的适应性后果来改变观察到的谱。我们研究了在存在和不存在强突变热点的情况下，不同营养环境对荧光假单胞菌 Pf0-2x（Pf0-1 的工程非运动衍生物）运动进化的影响。先前的研究表明，这种突变热点可以通过六个沉默突变来建立和破坏，这提供了快速获得突变的途径，从而挽救游泳活力并在特定环境中赋予最强的游泳表型。在这里，我们进化了 Pf0-2x 的热点和非热点变种菌株，用于在营养丰富（LB）和营养限制（M9）环境条件下的运动。我们观察到热点菌株在所有环境条件下始终进化得更快，并且其突变谱对环境差异具有鲁棒性。然而，非热点菌株具有独特的突变谱，该突变谱根据营养环境而变化。有趣的是，虽然营养丰富的环境中的替代适应性突变与热点突变的效果相同或较差，但营养有限的条件下的大多数突变都产生了优秀的游泳者。我们的竞争实验反映了这些发现，强调了环境在定义突变谱和相关表型强度方面的作用。这表明，虽然突变热点与自然选择协同作用可以加速获得强大的适应性突变（这可以在进化的种群中提供竞争优势），但它们可以限制对突变景观的探索，限制在特定环境中获得潜在更强的表型。
The observed mutational spectrum of adaptive outcomes can be constrained by many factors. For example, mutational biases can narrow the observed spectrum by increasing the rate of mutation at isolated sites in the genome. In contrast, complex environments can shift the observed spectrum by defining fitness consequences of mutational routes. We investigate the impact of different nutrient environments on the evolution of motility inPseudomonas fluorescensPf0-2x (an engineered non-motile derivative of Pf0-1) in the presence and absence of a strong mutational hotspot. Previous work has shown that this mutational hotspot can be built and broken via six silent mutations, which provide rapid access to a mutation that rescues swimming motility and confers the strongest swimming phenotype in specific environments. Here, we evolved a hotspot and non-hotspot variant strain of Pf0-2x for motility under nutrient-rich (LB) and nutrient-limiting (M9) environmental conditions. We observed the hotspot strain consistently evolved faster across all environmental conditions and its mutational spectrum was robust to environmental differences. However, the non-hotspot strain had a distinct mutational spectrum that changed depending on the nutrient environment. Interestingly, while alternative adaptive mutations in nutrient-rich environments were equal to, or less effective than, the hotspot mutation, the majority of these mutations in nutrient-limited conditions produced superior swimmers. Our competition experiments mirrored these findings, underscoring the role of environment in defining both the mutational spectrum and the associated phenotype strength. This indicates that while mutational hotspots working in concert with natural selection can speed up access to robust adaptive mutations (which can provide a competitive advantage in evolving populations), they can limit exploration of the mutational landscape, restricting access to potentially stronger phenotypes in specific environments.
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影响因子：
3.2
作者：
E. Robleto;I. López-Hernández;M. Silby;S. Levy
通讯作者：
E. Robleto;I. López-Hernández;M. Silby;S. Levy
影响因子：
11.4
作者：
Chandler, Christopher H.;Chari, Sudarshan;Dworkin, Ian
通讯作者：
Dworkin, Ian
DOI：
10.1101/sqb.2009.74.018
发表时间：
2009
期刊：
Cold Spring Harbor symposia on quantitative biology
影响因子：
--
作者：
Barrick JE;Lenski RE
通讯作者：
Lenski RE
影响因子：
7.7
作者：
Chappell CR;Dhami MK;Bitter MC;Czech L;Herrera Paredes S;Barrie FB;Calderón Y;Eritano K;Golden LA;Hekmat-Scafe D;Hsu V;Kieschnick C;Malladi S;Rush N;Fukami T
通讯作者：
Fukami T
影响因子：
16.8
作者：
Laessig, Michael;Mustonen, Ville;Walczak, Aleksandra M.
通讯作者：
Walczak, Aleksandra M.