Selection acts on DNA secondary structures to decrease transcriptional mutagenesis.

Selection acts on DNA secondary structures to decrease transcriptional mutagenesis.
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DOI:
10.1371/journal.pgen.0020176
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发表时间:
2006-11-03
期刊:
影响因子:
4.5
通讯作者:
Tenaillon O
Tenaillon O
中科院分区:
生物学2区
文献类型:
--
作者:
Hoede C;Denamur E;Tenaillon O

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单链DNA比双链DNA更容易发生突变。在转录过程中,DNA是瞬时单链的,因此受到更高的诱变。然而,如果形成局部链内二级结构,则一些碱基将配对,因此对突变的敏感性低于未配对的碱基。使用完整的基因组序列的大肠杆菌,我们表明,当地的链内二级结构,因此,可以用来定义一个指数的转录驱动的突变性。在基因水平上,我们表明,自然选择有利于减少转录驱动的诱变通过比预期的频率发生的链内二级结构。这种选择在高表达基因中更强,并表明控制突变率的序列依赖性方式和影响同义突变进化的新形式的选择。基因组序列进化是诱变和自然选择相互作用的结果。突变的发生是由于DNA的生物化学或物理改变和/或聚合酶在复制DNA时产生的错误。由于许多突变往往对生物体的适应性有害,自然选择有利于降低突变率。因此,许多机制已经进化来控制突变率。迄今为止描述的机制依赖于(i)修复受损DNA或校正错配碱基的酶的存在,这是对全基因组突变率有影响的机制,以及(ii)避免可能被聚合酶误读的重复序列,这是突变率的序列依赖性局部控制。在这篇论文中,作者认为存在另一种依赖于序列的突变控制,并塑造了基因组的整体进化。通过对大肠杆菌基因组的比较分析,他们表明,在基因转录成RNA过程中形成的局部二级结构可以调节碱基到碱基的突变率。此外,作者表明,自然选择似乎有利于这种结构的出现,以最大限度地减少突变性,特别是在大多数表达的基因中。本文提出了一种新的方式,基因序列可以限制自然选择。
Single-stranded DNA is more subject to mutation than double stranded. During transcription, DNA is transiently single stranded and therefore subject to higher mutagenesis. However, if local intra-strand secondary structures are formed, some bases will be paired and therefore less sensitive to mutation than unpaired bases. Using complete genome sequences of Escherichia coli, we show that local intra-strand secondary structures can, as a consequence, be used to define an index of transcription-driven mutability. At gene level, we show that natural selection has favoured a reduced transcription-driven mutagenesis via the higher than expected frequency of occurrence of intra-strand secondary structures. Such selection is stronger in highly expressed genes and suggests a sequence-dependent way to control mutation rates and a novel form of selection affecting the evolution of synonymous mutations. Genome sequence evolution results from the interplay between mutagenesis and natural selection. Mutations occur as the result of biochemical or physical alteration of DNA and/or from the errors made by polymerases while replicating DNA. As many mutations tend to be detrimental to the organism's fitness, natural selection favours a decrease in mutation rate. Hence, many mechanisms have evolved to control mutation rate. The mechanisms described to date have relied on (i) the existence of enzymes repairing the damaged DNA or correcting mismatched bases, which are mechanisms having an effect on whole genome mutation rate, and (ii) the avoidance in the sequence of repetition that could be misread by the polymerases, which is a sequence-dependent local control of mutation rate. In the present paper, the authors suggest that another sequence-dependent control of mutation exists and shapes the overall evolution of the genome. Using a comparative analysis of Escherichia coli genomes, they show that local secondary structures that are formed during the transcription of genes into RNA can modulate the base-to-base mutation rate. Moreover, the authors show that natural selection seems to have favoured the occurrence of such structures to minimise mutability, especially in the most expressed genes. This paper proposes a new way in which gene sequences can be constrained by natural selection.
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