Xia Xuhua
Department of Biology, University of Ottawa, 150 Louis, P.O. Box 450, Station A, Ottawa, Ontario, Canada K1N 6N5.
Gene. 2005 Jan 17;345(1):13-20. doi: 10.1016/j.gene.2004.11.019. Epub 2004 Dec 19.
The H-strand of vertebrate mitochondrial DNA is left single-stranded for hours during the slow DNA replication. This facilitates C-->U mutations on the H-strand (and consequently G-->A mutations on the L-strand) via spontaneous deamination which occurs much more frequently on single-stranded than on double-stranded DNA. For the 12 coding sequences (CDS) collinear with the L-strand, NNY synonymous codon families (where N stands for any of the four nucleotides and Y stands for either C or U) end mostly with C, and NNR and NNN codon families (where R stands for either A or G) end mostly with A. For the lone ND6 gene on the other strand, the codon bias is the opposite, with NNY codon families ending mostly with U and NNR and NNN codon families ending mostly with G. These patterns are consistent with the strand-specific mutation bias. The codon usage biased towards C-ending and A-ending in the 12 CDS sequences affects the codon-anticodon adaptation. The wobble site of the anticodon is always G for NNY codon families dominated by C-ending codons and U for NNR and NNN codon families dominated by A-ending codons. The only, but consistent, exception is the anticodon of tRNA-Met which consistently has a 5'-CAU-3' anticodon base-pairing with the AUG codon (the translation initiation codon) instead of the more frequent AUA. The observed CAU anticodon (matching AUG) would increase the rate of translation initiation but would reduce the rate of peptide elongation because most methionine codons are AUA, whereas the unobserved UAU anticodon (matching AUA) would increase the elongation rate at the cost of translation initiation rate. The consistent CAU anticodon in tRNA-Met suggests the importance of maximizing the rate of translation initiation.
在缓慢的DNA复制过程中，脊椎动物线粒体DNA的H链会单链暴露数小时。这通过自发脱氨作用促进了H链上的C→U突变（进而导致L链上的G→A突变），自发脱氨在单链DNA上发生的频率远高于双链DNA。对于与L链共线的12个编码序列（CDS），NNY同义密码子家族（其中N代表四种核苷酸中的任何一种，Y代表C或U）大多以C结尾，而NNR和NNN密码子家族（其中R代表A或G）大多以A结尾。对于另一条链上唯一的ND6基因，密码子偏好则相反，NNY密码子家族大多以U结尾，NNR和NNN密码子家族大多以G结尾。这些模式与链特异性突变偏好一致。12个CDS序列中偏向于以C结尾和以A结尾的密码子使用情况影响了密码子-反密码子的适配。对于以C结尾的密码子主导的NNY密码子家族，反密码子的摆动位点总是G，而对于以A结尾的密码子主导的NNR和NNN密码子家族，反密码子的摆动位点总是U。唯一但一致的例外是tRNA-Met的反密码子，它始终具有5'-CAU-3'反密码子，与AUG密码子（翻译起始密码子）碱基配对，而不是更常见的AUA。观察到的CAU反密码子（与AUG匹配）会提高翻译起始速率，但会降低肽链延伸速率，因为大多数甲硫氨酸密码子是AUA，而未观察到的UAU反密码子（与AUA匹配）会以翻译起始速率为代价提高延伸速率。tRNA-Met中一致的CAU反密码子表明最大化翻译起始速率的重要性。
