Epistatic interactions between ancestral genotype and beneficial mutations shape evolvability in Pseudomonas aeruginosa
Epistatic interactions between ancestral genotype and beneficial mutations shape evolvability in Pseudomonas aeruginosa
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DOI：
10.1111/evo.12958
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发表时间：
2016-07-01
期刊：
影响因子：
3.3
通讯作者：
MacLean, R. Craig
中科院分区：
文献类型：
--
作者：
Gifford, Danna R.;Toll-Riera, Macarena;MacLean, R. Craig
突变之间的相互作用通过推动种群在适应环境中达到低适应度和高适应度高峰来影响适应的想法在进化理论中根深蒂固。在这里，我们研究了上位性对进化的影响，通过挑战两个携带不同初始突变(rpoB中的导致利福平耐药性的rpoB和IV型菌毛基因网络)的铜绿假单胞菌克隆的种群来适应以L-丝氨酸为唯一碳源的培养基。尽管最初在适应度上无法区分，但由这两种祖先基因建立的种群在经过300代进化后达到了不同的适应度。基因组测序显示，这种差异不能用获得不同选择目标的突变来解释；来自两个祖先的大多数克隆都集中在以下两种策略之一：(1)获得PA2449(gcsR，L丝氨酸代谢RpoN增强子结合蛋白)的突变或(2)蛋白酶基因的突变。此外，来自两个祖先的种群聚集在IV型菌毛基因网络中的功能丧失突变上，这可能是由于祖先或后天突变造成的。没有在RNA聚合酶(RNAP)基因中观察到补偿性或逆转突变，尽管通常与rpoB突变相关的适应成本很高。尽管目前的理论指出上位性是对进化性的主要制约，但这些结果表明，大小上位性在限制进化性方面的作用可能被低估了。在生物相关的突变供应率下，幅度上位性的贡献可能最大，这使得返回突变的可能性不大。
The idea that interactions between mutations influence adaptation by driving populations to low and high fitness peaks on adaptive landscapes is deeply ingrained in evolutionary theory. Here, we investigate the impact of epistasis on evolvability by challenging populations of two Pseudomonas aeruginosa clones bearing different initial mutations (in rpoB conferring rifampicin resistance, and the type IV pili gene network) to adaptation to a medium containing L-serine as the sole carbon source. Despite being initially indistinguishable in fitness, populations founded by the two ancestral genotypes reached different fitness following 300 generations of evolution. Genome sequencing revealed that the difference could not be explained by acquiring mutations in different targets of selection; the majority of clones from both ancestors converged on one of the following two strategies: (1) acquiring mutations in either PA2449 (gcsR, an L-serine-metabolism RpoN enhancer binding protein) or (2) protease genes. Additionally, populations from both ancestors converged on loss-of-function mutations in the type IV pili gene network, either due to ancestral or acquired mutations. No compensatory or reversion mutations were observed in RNA polymerase (RNAP) genes, in spite of the large fitness costs typically associated with mutations in rpoB. Although current theory points to sign epistasis as the dominant constraint on evolvability, these results suggest that the role of magnitude epistasis in constraining evolvability may be underappreciated. The contribution of magnitude epistasis is likely to be greatest under the biologically relevant mutation supply rates that make back mutations probabilistically unlikely.