Systematic asymmetric nucleotide exchanges produce human mitochondrial RNAs cryptically encoding for overlapping protein coding genes
Systematic asymmetric nucleotide exchanges produce human mitochondrial RNAs cryptically encoding for overlapping protein coding genes
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DOI：
10.1016/j.jtbi.2013.01.024
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发表时间：
2013-05-07
影响因子：
2
通讯作者：
Seligmann, Herve
中科院分区：
文献类型：
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作者：
Seligmann, Herve
GenBank的EST数据库包括与人类线粒体序列完全匹配的RNA，假设系统性不对称核苷酸交换-转录沿着交换规则：A -> G -> C -> U/T -> A（12个EST）、A -> U/T -> C -> G -> A（4个EST）、C -> G -> U/T -> C（3个EST）和A -> C -> G -> U/T -> A（1个EST），no RNA对应于其他潜在的不对称交换规则。从核苷酸交换的人线粒体蛋白编码基因翻译的假设多肽与许多GenBank蛋白比对，预测的二级结构类似于其推定的GenBank同源物。两个独立的方法，旨在检测重叠的基因（一个基于核苷酸含量分析的复制脱氨基梯度在第三密码子的位置，和循环密码分析的密码子内容的基础上的框架冗余），确认核苷酸交换加密的重叠基因。方法集中在哪些基因最可能是活跃的，哪些不是，这是各种交换规则。由不同核苷酸交换产生的平均EST长度与（a）各种生物信息学分析证实推定的重叠基因的蛋白质编码状态的程度;（B）通过人线粒体DNA聚合酶γ的相应核苷酸取代的已知动力学化学参数成比例（核苷酸DNA错误插入率）;（c）预测的重叠基因中的终止密码子密度（终止密码子通读和交换聚合通过相互平衡来调节基因表达）。许多很少表达的蛋白质似乎通过不对称核苷酸交换在常规线粒体基因中编码，避免延长基因组。几种独立方法之间的交叉证据证实了系统核苷酸交换基因加密的工作假设状态。(C)2013爱思唯尔有限公司保留所有权利。
GenBank's EST database includes RNAs matching exactly human mitochondrial sequences assuming systematic asymmetric nucleotide exchange-transcription along exchange rules: A -> G -> C -> U/T -> A (12 ESTs), A -> U/T -> C -> G -> A (4 ESTs), C -> G -> U/T -> C (3 ESTs), and A -> C -> G -> U/T -> A (1 EST), no RNAs correspond to other potential asymmetric exchange rules. Hypothetical polypeptides translated from nucleotide-exchanged human mitochondrial protein coding genes align with numerous GenBank proteins, predicted secondary structures resemble their putative GenBank homologue's. Two independent methods designed to detect overlapping genes (one based on nucleotide contents analyses in relation to replicative deamination gradients at third codon positions, and circular code analyses of codon contents based on frame redundancy), confirm nucleotide-exchange-encrypted overlapping genes. Methods converge on which genes are most probably active, and which not, and this for the various exchange rules. Mean EST lengths produced by different nucleotide exchanges are proportional to (a) extents that various bioinformatics analyses confirm the protein coding status of putative overlapping genes; (b) known kinetic chemistry parameters of the corresponding nucleotide substitutions by the human mitochondrial DNA polymerase gamma (nucleotide DNA misinsertion rates); (c) stop codon densities in predicted overlapping genes (stop codon readthrough and exchanging polymerization regulate gene expression by counterbalancing each other). Numerous rarely expressed proteins seem encoded within regular mitochondrial genes through asymmetric nucleotide exchange, avoiding lengthening genomes. Intersecting evidence between several independent approaches confirms the working hypothesis status of gene encryption by systematic nucleotide exchanges. (C) 2013 Elsevier Ltd. All rights reserved.