Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
BMC Evol Biol. 2010 Jun 18;10:187. doi: 10.1186/1471-2148-10-187.
The interplay between transcription and mutational processes can lead to particular mutation patterns in transcribed regions of the genome. Transcription introduces several biases in mutational patterns; in particular it invokes strand specific mutations. In order to understand the forces that have shaped transcripts during evolution, one has to study mutation patterns associated with transcription across animals.
Using multiple alignments of related species we estimated the regional single-nucleotide substitution patterns along genes in four vertebrate taxa: primates, rodents, laurasiatheria and bony fishes. Our analysis is focused on intronic and intergenic regions and reveals differences in the patterns of substitution asymmetries between mammals and fishes. In mammals, the levels of asymmetries are stronger for genes starting within CpG islands than in genes lacking this property. In contrast to all other species analyzed, we found a mutational pressure in dog and stickleback, promoting an increase of GC-contents in the proximity to transcriptional start sites.
We propose that the asymmetric patterns in transcribed regions are results of transcription associated mutagenic processes and transcription coupled repair, which both seem to evolve in a taxon related manner. We also discuss alternative mechanisms that can generate strand biases and involves error prone DNA polymerases and reverse transcription. A localized increase of the GC content near the transcription start site is a signature of biased gene conversion (BGC) that occurs during recombination and heteroduplex formation. Since dog and stickleback are known to be subject to rapid adaptations due to population bottlenecks and breeding, we further hypothesize that an increase in recombination rates near gene starts has been part of an adaptive process.
转录和突变过程之间的相互作用会导致基因组转录区域出现特定的突变模式。转录会在突变模式中引入多种偏向性，尤其是会引起链特异性突变。为了了解在进化过程中是什么力量塑造了转录本，我们必须研究跨越动物的转录相关的突变模式。
我们使用相关物种的多重比对，估计了四个脊椎动物类群（灵长类动物、啮齿动物、劳亚兽和硬骨鱼）中基因的区域单核苷酸取代模式。我们的分析集中在内含子和基因间区，并揭示了哺乳动物和鱼类之间取代不对称模式的差异。在哺乳动物中，起始于 CpG 岛的基因的不对称水平要强于缺乏这种特性的基因。与分析的所有其他物种不同，我们在狗和刺鱼中发现了一种促进转录起始位点附近 GC 含量增加的突变压力。
我们提出，转录区域中的不对称模式是与转录相关的诱变过程和转录偶联修复的结果，这两者似乎都以与分类群相关的方式进化。我们还讨论了其他可以产生链偏向性的替代机制，涉及易错 DNA 聚合酶和逆转录。在转录起始位点附近 GC 含量的局部增加是偏向基因转换（BGC）的特征，它发生在重组和异源双链体形成过程中。由于狗和刺鱼由于种群瓶颈和繁殖而迅速适应，我们进一步假设基因起始附近重组率的增加是适应过程的一部分。
