Gene inversion potentiates bacterial evolvability and virulence.
Gene inversion potentiates bacterial evolvability and virulence.
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DOI：
10.1038/s41467-018-07110-3
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发表时间：
2018-11-07
影响因子：
16.6
通讯作者：
Merrikh H
中科院分区：
文献类型：
--
作者：
Merrikh CN;Merrikh H
大多数细菌基因编码在前导链上，与RNA聚合酶共同定向复制机器的运动。这种偏差减少了两台机器之间有害的正面碰撞的频率。这些碰撞的负面结果应该会导致对迎面等位基因的选择，最大限度地提高基因组的共同取向。我们的发现挑战了这一模式。使用GC偏斜计算，我们揭示了多种不同细菌病原体中所有染色体编码基因的进化反转记录。与预期相反，我们发现大量的共定向基因已经反转为正面定向，这可能增加了正面复制-转录冲突的频率。此外，我们发现，头对基因（包括关键的抗生素抗性和毒力基因）具有更高的非同义突变率，并且更频繁地处于正选择（dN/dS > 1）下。基于这些结果，我们提出，自发基因倒位可以通过迎面复制-转录碰撞来增加细菌的进化能力和致病能力。迎面而来的复制-转录碰撞发生在落后DNA链上编码的基因内。在这里，作者表明，大量最初的共同取向（前导链）基因已经反转为正面取向，增加了基因特异性突变率和几种细菌病原体的整体可进化性。
Most bacterial genes are encoded on the leading strand, co-orienting the movement of the replication machinery with RNA polymerases. This bias reduces the frequency of detrimental head-on collisions between the two machineries. The negative outcomes of these collisions should lead to selection against head-on alleles, maximizing genome co-orientation. Our findings challenge this model. Using the GC skew calculation, we reveal the evolutionary inversion record of all chromosomally encoded genes in multiple divergent bacterial pathogens. Against expectations, we find that a large number of co-oriented genes have inverted to the head-on orientation, presumably increasing the frequency of head-on replication-transcription conflicts. Furthermore, we find that head-on genes, (including key antibiotic resistance and virulence genes) have higher rates of non-synonymous mutations and are more frequently under positive selection (dN/dS > 1). Based on these results, we propose that spontaneous gene inversions can increase the evolvability and pathogenic capacity of bacteria through head-on replication-transcription collisions. Head-on replication-transcription collisions occur within genes encoded on the lagging DNA strand. Here, the authors show that a large number of originally co-oriented (leading strand) genes have inverted to the head-on orientation, increasing both gene-specific mutation rates, and the overall evolvability of several bacterial pathogens.
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影响因子：
56.9
作者：
de Visser, JAGM;Zeyl, CW;Lenski, RE
通讯作者：
Lenski, RE
影响因子：
10.7
作者：
Fonseca, Miguel M.;Posada, David;Harris, D. James
通讯作者：
Harris, D. James
转录复制冲突取向调节R环水平并激活不同的DNA损伤反应。
影响因子：
64.5
作者：
Hamperl S;Bocek MJ;Saldivar JC;Swigut T;Cimprich KA
通讯作者：
Cimprich KA
分枝杆菌的鉴定和测序。
影响因子：
3.7
作者：
Li Y;Chen W;Wang Y;Luo K;Li Y;Bai L;Luo F
通讯作者：
Luo F
影响因子：
3.9
作者：
Mackiewicz, P;Mackiewicz, D;Cebrat, S
通讯作者：
Cebrat, S