Plasmid fitness costs are caused by specific genetic conflicts enabling resolution by compensatory mutation.
Plasmid fitness costs are caused by specific genetic conflicts enabling resolution by compensatory mutation.
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DOI：
10.1371/journal.pbio.3001225
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发表时间：
2021-10
期刊：
影响因子：
9.8
通讯作者：
Brockhurst MA
中科院分区：
文献类型：
--
作者：
Hall JPJ;Wright RCT;Harrison E;Muddiman KJ;Wood AJ;Paterson S;Brockhurst MA
质粒在细菌基因组进化中起着重要的作用，它通过基因在谱系之间转移。与携带质粒相关的适合度成本被认为是基因交换的障碍，但质粒适合度成本的原因却知之甚少。单个补偿性突变通常足以完全改善质粒适合性成本，这表明这种成本是由特定的遗传冲突引起的，而不是由质粒的一般属性引起的，如它们的大小、代谢负担或基因表达水平。通过将实验进化的结果与遗传学和转录组学相结合，我们证明荧光假单胞菌中两个不同的大质粒的适合性成本是由于诱导染色体尾黄素毒素操纵子的不适应表达造成的。单个基因的突变与毒素操纵子无关，位于染色体或质粒上，改善了与携带质粒相关的中断。我们发现其中一个补偿基因，染色体基因PFLU4242，是两个质粒适应成本的关键调节因子，另一个补偿基因要么降低该基因的表达，要么通过上调假定的质粒携带的Parab操纵子来减轻其有害影响。染色体可移动遗传元件Tn6291使用质粒进行传递，即使在补偿菌株中也保持上调，这表明可移动遗传元件通过独立于一般生理干扰的途径进行通信。由特定遗传冲突引起的质粒适应成本不太可能成为水平基因转移(HGT)的长期障碍，因为它们倾向于通过单一补偿突变来改善，这有助于解释为什么质粒在细菌基因组中如此常见。质粒给宿主带来了健康成本，但其潜在的机制尚不清楚。这项研究表明，特定的基因相互作用，而不是一般的性质，如其大小，是主要负责的负担，质粒施加。这种冲突的倾向可以通过单一的代偿性突变来改善，这可能有助于解释为什么质粒如此普遍。
Plasmids play an important role in bacterial genome evolution by transferring genes between lineages. Fitness costs associated with plasmid carriage are expected to be a barrier to gene exchange, but the causes of plasmid fitness costs are poorly understood. Single compensatory mutations are often sufficient to completely ameliorate plasmid fitness costs, suggesting that such costs are caused by specific genetic conflicts rather than generic properties of plasmids, such as their size, metabolic burden, or gene expression level. By combining the results of experimental evolution with genetics and transcriptomics, we show here that fitness costs of 2 divergent large plasmids in Pseudomonas fluorescens are caused by inducing maladaptive expression of a chromosomal tailocin toxin operon. Mutations in single genes unrelated to the toxin operon, and located on either the chromosome or the plasmid, ameliorated the disruption associated with plasmid carriage. We identify one of these compensatory loci, the chromosomal gene PFLU4242, as the key mediator of the fitness costs of both plasmids, with the other compensatory loci either reducing expression of this gene or mitigating its deleterious effects by up-regulating a putative plasmid-borne ParAB operon. The chromosomal mobile genetic element Tn6291, which uses plasmids for transmission, remained up-regulated even in compensated strains, suggesting that mobile genetic elements communicate through pathways independent of general physiological disruption. Plasmid fitness costs caused by specific genetic conflicts are unlikely to act as a long-term barrier to horizontal gene transfer (HGT) due to their propensity for amelioration by single compensatory mutations, helping to explain why plasmids are so common in bacterial genomes. Plasmids impose fitness costs on their hosts, but the underlying mechanisms have been unclear. This study shows that specific gene interactions, rather than general properties of plasmids such as their size, are principally responsible for the burden plasmids impose. The propensity of such conflicts to be ameliorated by single compensatory mutations may help to explain why plasmids are so widespread.
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