Evolutionary accessibility of mutational pathways.
Evolutionary accessibility of mutational pathways.
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DOI：
10.1371/journal.pcbi.1002134
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发表时间：
2011-08
影响因子：
4.3
通讯作者：
Krug J
中科院分区：
文献类型：
--
作者：
Franke J;Klözer A;de Visser JA;Krug J
已知不同突变的功能影响以非常重要的方式结合到总影响中。对于进化选择下的性状（“适应度”），一组突变的所有可能组合的测量值产生了适应度景观，该景观决定了从给定的初始基因型可以达到哪些突变状态。理解适应性景观的可达性属性对于回答关于进化适应的可预测性和可重复性的问题具有重要的概念意义。在这里，我们从理论上研究了各种模型景观的全局最优状态的可达性，包括具有可调崎岖度的景观以及中性的“空洞”景观。我们定义一个突变途径，如果它包含达到目标基因型所需的最小数量的突变，并且如果适应度在每个突变步骤中增加。在这个定义下，可达性是高的，也就是说，随着适应度景观的维数（由突变位点的数量设定）变大，至少有一条可达路径以相当大的概率接近于1。与此同时，可供选择的可访问路径的数量无限制地增长。我们对丝状真菌黑曲霉获得的经验8位点适应度景观进行了模型预测。通过分析包含不同突变子集的完整景观子图，我们能够探索经验数据中的突变距离尺度。高可达性的预测效果得到了经验数据的支持，并且非常稳健，我们认为这反映了序列空间的一般拓扑结构。再加上我们对可及性定义中的限制性假设，这意味着全基因组进化应该可以获得全局最优配置，但由于存在大量可选突变途径，进化轨迹的可重复性受到限制。适应度景观描述了特定环境下相关基因型的适应度，并可用于确定在特定进化情景下哪些突变步骤导致更高的适应度。适应度景观的结构是由突变在决定适应度时相互作用的方式决定的，当突变具有乘法效应时，它可以是平滑的，当相互作用强且符号相反时，它可以是崎岖的。人们对真正的健身景观的结构知之甚少。在此，我们利用不同的景观模型研究了适应度景观的进化可达性，并将结果与真菌黑曲霉（Aspergillus niger） 8个标记突变的适应度景观进行了比较。我们的问题是，在每一步都增加适应度的意义上，有多少从低适应度到全局最优基因型的突变途径可以通过自然选择获得。我们发现，对于所有低于最大崎岖度的景观，尽管每个路径的可达性都有所下降，但可达路径的数量随着所涉及的位点数量的增加而增加。我们还发现，具有中等坚固度的模型最能描述黑桫树的数据。
Functional effects of different mutations are known to combine to the total effect in highly nontrivial ways. For the trait under evolutionary selection (‘fitness’), measured values over all possible combinations of a set of mutations yield a fitness landscape that determines which mutational states can be reached from a given initial genotype. Understanding the accessibility properties of fitness landscapes is conceptually important in answering questions about the predictability and repeatability of evolutionary adaptation. Here we theoretically investigate accessibility of the globally optimal state on a wide variety of model landscapes, including landscapes with tunable ruggedness as well as neutral ‘holey’ landscapes. We define a mutational pathway to be accessible if it contains the minimal number of mutations required to reach the target genotype, and if fitness increases in each mutational step. Under this definition accessibility is high, in the sense that at least one accessible pathway exists with a substantial probability that approaches unity as the dimensionality of the fitness landscape (set by the number of mutational loci) becomes large. At the same time the number of alternative accessible pathways grows without bounds. We test the model predictions against an empirical 8-locus fitness landscape obtained for the filamentous fungus Aspergillus niger. By analyzing subgraphs of the full landscape containing different subsets of mutations, we are able to probe the mutational distance scale in the empirical data. The predicted effect of high accessibility is supported by the empirical data and is very robust, which we argue reflects the generic topology of sequence spaces. Together with the restrictive assumptions that lie in our definition of accessibility, this implies that the globally optimal configuration should be accessible to genome wide evolution, but the repeatability of evolutionary trajectories is limited owing to the presence of a large number of alternative mutational pathways. Fitness landscapes describe the fitness of related genotypes in a given environment, and can be used to identify which mutational steps lead towards higher fitness under particular evolutionary scenarios. The structure of a fitness landscape results from the way mutations interact in determining fitness, and can be smooth when mutations have multiplicative effect or rugged when interactions are strong and of opposite sign. Little is known about the structure of real fitness landscapes. Here, we study the evolutionary accessibility of fitness landscapes by using various landscape models with tunable ruggedness, and compare the results with an empirical fitness landscape involving eight marker mutations in the fungus Aspergillus niger. We ask how many mutational pathways from a low-fitness to the globally optimal genotype are accessible by natural selection in the sense that each step increases fitness. We find that for all landscapes with lower than maximal ruggedness the number of accessible pathways increases with increases of the number of loci involved, despite decreases in the accessibility for each pathway individually. We also find that models with intermediate ruggedness describe the A. niger data best.
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影响因子：
3.3
作者：
Jain, Kavita;Krug, Joachim
通讯作者：
Krug, Joachim
DOI：
10.1073/pnas.0906192106
发表时间：
2010-01-26
影响因子：
11.1
作者：
Carneiro, Mauricio;Hartl, Daniel L.
通讯作者：
Hartl, Daniel L.
影响因子：
3.3
作者：
da Silva, Jack;Coetzer, Mia;Mosier, Donald E.
通讯作者：
Mosier, Donald E.
影响因子：
2.9
作者：
Dawid, Alexandre;Kiviet, Daniel J.;Tans, Sander J.
通讯作者：
Tans, Sander J.
影响因子：
2
作者：
Gokhale, Chaitanya S.;Iwasa, Yoh;Nowak, Martin A.;Traulsen, Arne
通讯作者：
Traulsen, Arne