Genic Incompatibilities in Two Hybrid Bacteriophages
Genic Incompatibilities in Two Hybrid Bacteriophages
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DOI：
10.1093/molbev/msp199
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发表时间：
2009-12-01
影响因子：
10.7
通讯作者：
Wichman, Holly A.
中科院分区：
文献类型：
--
作者：
Rokyta, Darin R.;Wichman, Holly A.
水平基因转移和重组在微生物进化中发挥着重要作用，并在不同的群体中被发现，包括许多与医学相关的群体，如艾滋病毒和登革热病毒。在缺乏机制障碍的情况下，特定重组事件的进化成功取决于重组基因型是否因基因组内有利的上位相互作用的破坏而遭受适应性成本，如果是这样，这种适应性成本可能在多大程度上被随后的补偿性进化所减轻。为了研究基因之间上位性相互作用的重要性以及不同祖先基因型之间同源重组事件的进化可行性，我们通过交换编码外壳蛋白基因的等位基因构建了两个重组微病毒噬菌体。该基因的编码序列在氨基酸水平上相差约8%，并且在两个与phi X174相关的祖先噬菌体之间互换，并且很好地适应了它们的培养条件。由于重组噬菌体的适应度大大降低，我们通过对每个噬菌体的复制系进行选择，进一步探索了它们的进化能力。我们发现，所有四个谱系在短短60代内就实现了与祖先适应度相称的适应度，平均而言，第一次替换占总适应度恢复的一半以上。适应性恢复需要在每个谱系中进行3到5次替换，总共涉及9个基本噬菌体基因中的8个，这表明整个基因组中存在广泛的上位性相互作用。有趣的是，与病毒衣壳中交换的蛋白质有最广泛和最明显的物理相互作用的蛋白质似乎在适应性恢复中没有多大作用。这一结果似乎是相互作用中氨基酸残基守恒的结果。这表明，在产生基因不相容方面，强上位性相互作用不如弱的、短暂的相互作用重要，因为它们排除了蛋白质相互作用区域的变异性。
Horizontal gene transfer and recombination play a major role in microbial evolution and have been detected in diverse groups, including many of medical relevance such as HIV and dengue virus. In the absence of mechanistic barriers, the evolutionary success of a particular recombination event is determined by whether the recombinant genotype suffers a fitness cost through the disruption of favorable epistatic interactions within the genome, and if so, the extent to which this fitness cost might be mitigated by subsequent compensatory evolution. To investigate the importance of epistatic interactions between genes and the evolutionary viability of a homologous recombination event between diverged ancestral genotypes, we constructed two recombinant microvirid bacteriophages by exchanging their alleles of the gene encoding the coat protein. The coding sequences for this gene differ by approximately 8% at the amino acid level and were interchanged between two ancestral phages related to phi X174 and well adapted to their culture conditions. Because the recombinant phages showed drastically reduced fitnesses, we further explored their evolutionary viability by subjecting replicate lines of each of them to selection. We found that all four lineages achieved fitnesses commensurate with ancestral fitnesses in as few as 60 generations, and on average, the first substitution accounted for more than half of the total fitness recovery. Fitness recovery required three to five substitutions in each lineage, and overall eight of the nine essential phage genes were involved, suggesting extensive epistatic interactions throughout the genome. Interestingly, the proteins with the most extensive and apparent physical interactions with the exchanged protein in the viral capsid did not appear to have much of a role in fitness recovery. This result appears to be a consequence of the conservation of the amino acid residues involved in the interactions. It suggests that strong epistatic interactions are less important than weaker, transient ones in producing genic incompatibilities because they preclude variability in the interacting regions of the proteins.