Estimation of DNA sequence context-dependent mutation rates using primate genomic sequences.
Estimation of DNA sequence context-dependent mutation rates using primate genomic sequences.
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使用灵长类基因组序列估计 DNA 序列上下文相关的突变率。
DOI：
10.1007/s00239-007-9000-5
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发表时间：
2007
影响因子：
3.9
通讯作者：
NISCComparativeSequencingProgram
中科院分区：
文献类型：
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作者：
Zhang,Wei;Bouffard,GerardG;Wallace,SusanS;Bond,JeffreyP;NISCComparativeSequencingProgram
应当理解，DNA和氨基酸取代率是高度序列上下文依赖性的，例如，脊椎动物中的C→T置换可能更频繁地发生在CpG位点，并且半胱氨酸置换率可能取决于参与二硫键的背景支持。此外，许多应用依赖于核苷酸或氨基酸取代的定量模型，包括系统发育推断和鉴定涉及功能特异性的氨基酸序列位置。我们描述了使用NISC比较测序计划生成的狒狒、黑猩猩和人类基因组序列数据对核苷酸取代率的上下文依赖性进行量化。基于最大似然计算，报告了96类5′αβγ3′ → 5′αδγ3′突变的相对突变率，其中α、β、γ和δ为核苷酸，β为δ。我们的研究结果证实，C→T取代增强CpG位点相比，其他转换，相对独立的身份前面的核苷酸。虽然，正如预期的那样，转换通常比颠换更频繁地发生，我们发现，最常见的颠换涉及在CpG位点的C（CpG颠换），其速率是在非CpG位点的转换速率相当。灵长类DNA序列的上下文依赖性进化速率的四类模型，CpG转换>非CpG转换→ CpG颠换>非CpG颠换，捕获突变谱的定性特征。我们发现，尽管不同的基因组区域之间的突变率定性相似，有统计学上的显着差异。
It is understood that DNA and amino acid substitution rates are highly sequence context-dependent, e.g., C→T substitutions in vertebrates may occur much more frequently at CpG sites and that cysteine substitution rates may depend on support of the context for participation in a disulfide bond. Furthermore, many applications rely on quantitative models of nucleotide or amino acid substitution, including phylogenetic inference and identification of amino acid sequence positions involved in functional specificity. We describe quantification of the context dependence of nucleotide substitution rates using baboon, chimpanzee, and human genomic sequence data generated by the NISC Comparative Sequencing Program. Relative mutation rates are reported for the 96 classes of mutations of the form 5′αβγ3′ → 5′αδγ3′, where α, β, γ, and δ are nucleotides and β ≠ δ, based on maximum likelihood calculations. Our results confirm that C→T substitutions are enhanced at CpG sites compared with other transitions, relatively independent of the identity of the preceding nucleotide. While, as expected, transitions generally occur more frequently than transversions, we find that the most frequent transversions involve the C at CpG sites (CpG transversions) and that their rate is comparable to the rate of transitions at non-CpG sites. A four-class model of the rates of context-dependent evolution of primate DNA sequences, CpG transitions > non-CpG transitions ≈ CpG transversions > non-CpG transversions, captures qualitative features of the mutation spectrum. We find that despite qualitative similarity of mutation rates among different genomic regions, there are statistically significant differences.