The Accelerated Evolution of Lagging Strand Genes Is Independent of Sequence Context.
The Accelerated Evolution of Lagging Strand Genes Is Independent of Sequence Context.
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滞后链基因的加速进化与序列背景无关。
DOI：
10.1093/gbe/evw274
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发表时间：
2016
影响因子：
3.3
通讯作者：
Merrikh,Houra
中科院分区：
文献类型：
--
作者：
Merrikh,ChristopherN;Weiss,Eli;Merrikh,Houra
我们之前发现，枯草芽孢杆菌（以及潜在的其他细菌）的后链基因进化得更快。后链基因在DNA复制方面以正面方向转录，导致两种机器之间的碰撞，从而阻止复制并可能破坏基因组的稳定。我们之前的工作表明，正面基因突变的增加依赖于转录偶联修复和一种容易出错的聚合酶的活性，这种聚合酶可能在这些碰撞的反应中被激活。最近，有人提出，序列上下文是增加突变和进化的迎面基因的主要贡献者。这些模型是基于在b进行的基于实验室的进化实验。细小。然而，野生菌株自然发生的单核苷酸多态性（SNPs）的关键进化分析没有进行。利用9种亲缘关系密切的野生物种的基因组序列。我们分析了超过20万个自然发生的snp，作为所有基因，特别是正面基因的自然突变模式的代表。我们的分析表明（框架无关的）三胞胎序列上下文可以影响突变率：某些三胞胎序列（TAG、CCC、CTA和ACC）以更高的速率积累snp，并从基因组中消失。然而，先前在实验室实验中被鉴定为诱变的三联体序列（CCG、GCG和CAC）并没有增加SNP积累的速率，也没有从基因组中消失。重要的是，dN/dS分析表明，正面基因的加速进化并不依赖于任何特定的三联体序列。因此，与我们之前的结果一致，诱变转录偶联修复，而不是序列背景，足以解释迎面基因的加速进化。
We previously discovered that lagging strand genes evolve faster inBacillus subtilis(and potentially other bacteria). Lagging strand genes are transcribed in the head-on orientation with respect to DNA replication, leading to collisions between the two machineries that stall replication and can destabilize genomes. Our previous work indicated that the increased mutagenesis of head-on genes depends on transcription-coupled repair and the activity of an error prone polymerase which is likely activated in response to these collisions. Recently, it was proposed that sequence context is a major contributor to the increased mutagenesis and evolution of head-on genes. These models are based on laboratory-based evolution experiments performed inB. subtilis. However, critical evolutionary analyses of naturally occurring single nucleotide polymorphisms (SNPs) in wild strains were not performed. Using the genomic sequences from nine closely related wildB. subtilisstrains, we analyzed over 200,000 naturally occurring SNPs as a proxy for natural mutation patterns for all genes and in particular, head-on genes. Our analysis suggests that (frame-independent) triplet sequence context can impact mutation rates: certain triplet sequences (TAG, CCC, CTA, and ACC) accumulate SNPs at a higher rate and are depleted from the genome. However, the triplet sequences previously identified as mutagenic in laboratory experiments (CCG, GCG, and CAC) do not have an elevated rate of SNP accumulation and are not depleted from the genome. Importantly, dN/dS analyses indicate that the accelerated evolution of head-on genes is not dependent on any particular triplet sequence. Thus, in agreement with our previous results, mutagenic transcription-coupled repair, rather than sequence context, is sufficient to explain the accelerated evolution of head-on genes.