Detecting gradients of asymmetry in site-specific substitutions in mitochondrial genomes.
Detecting gradients of asymmetry in site-specific substitutions in mitochondrial genomes.
复制标题
检测线粒体基因组中位点特异性取代的不对称梯度。
DOI：
10.1089/dna.2004.23.707
复制
发表时间：
2004
影响因子：
3.1
通讯作者：
Pollock,DavidD
中科院分区：
文献类型：
--
作者：
Krishnan,NeerajaM;Seligmann,Hervè;Raina,SameerZ;Pollock,DavidD
在线粒体复制过程中，自发突变发生，并在重链（DssH）单链所花费的时间内不对称地积累。主要的突变似乎是从腺嘌呤到次黄嘌呤（A →H，导致A →G取代）和胞嘧啶到胸腺嘧啶（C → T）的脱氨基。以前的研究结果表明，C →T置换迅速积累，然后在高DssH饱和，表明保护或修复，而A →G与DssH线性积累。我们在这里描述了一个简单的隐马尔可夫模型（HMM）的实现，以提供一个几乎连续的配置文件的不对称性，在任何特定的替代类型的替代反应。我们实现了这个模型，使用基于贝叶斯马尔可夫链蒙特卡罗（MCMC）的方法。我们比较和对比所有12种可能的替代类型的相对不对称性，发现使用我们的新方法确定的观察到的过渡替代响应与以前的预测C →T过渡替代的饱和曲线和A →G过渡的线性累积相当吻合。在颠换取代中看到的模式显示出低得多的位点变异，并且是非线性的，比在转换中看到的更复杂。我们还发现，在考虑了主线性效应之后，A →G/G→A响应比率中的一些残余变化可以通过一个位点处的平均预测核酸二级结构倾向来解释，这可能是由于二级结构形成时对突变的保护。
During mitochondrial replication, spontaneous mutations occur and accumulate asymmetrically during the time spent single stranded by the heavy strand (DssH). The predominant mutations appear to be deaminations from adenine to hypoxanthine (A →H, which leads to an A →G substitution) and cytosine to thymine (C → T). Previous findings indicated that C →T substitutions accumulate rapidly and then saturate at high DssH, suggesting protection or repair, whereas A →G accumulates linearly with DssH. We describe here the implementation of a simple hidden Markov model (HMM) of among-site rate correlations to provide an almost continuous profile of the asymmetry in substitution response for any particular substitution type. We implement this model using a phylogeny-based Bayesian Markov chain Monte Carlo (MCMC) approach. We compare and contrast the relative asymmetries in all 12 possible substitution types, and find that the observed transition substitution responses determined using our new method agree quite well with previous predictions of a saturating curve for C →T transition substitutions and a linear accumulation of A →G transitions. The patterns seen in transversion substitutions show much lower among-site variation, and are nonlinear and more complex than those seen in transitions. We also find that, after accounting for the principal linear effect, some of the residual variation in A →G/G→A response ratios is explained by the average predicted nucleic acid secondary structure propensity at a site, possibly due to protection from mutation when secondary structure forms.