Asymmetrical directional mutation pressure in the mitochondrial genome of mammals
Asymmetrical directional mutation pressure in the mitochondrial genome of mammals
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DOI：
10.1093/oxfordjournals.molbev.a026011
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发表时间：
1998-08-01
影响因子：
10.7
通讯作者：
Saccone, C
中科院分区：
文献类型：
--
作者：
Reyes, A;Gissi, C;Saccone, C
考虑到 H 链基因的所有三个密码子位置 (P-123) 和四重简并位点 (P-4FD)，分析了 25 个完整哺乳动物线粒体 (mt) 基因组的碱基组成。在非转录 L 链中，G 是代表性较少的碱基，A 是所有情况下代表性最多的碱基，而 C 和 T 因物种而异。 H 链蛋白质编码基因显示两条链之间四个碱基的不对称分布。 P-4FD上的不对称指数AT和GC偏度远高于P-123，表明存在不对称定向突变压力。为了找到一种可能的机制来解释这种不对称性的起源，人们对组成特征与转录或复制过程之间的关系进行了研究。 AT 和 GC 偏差、四重简并位点的碱基组成以及每个基因的可变位点数量与 H 链基因在复制过程中单链状态的持续时间显着相关。我们测试了不同的复制相关假设，例如是否存在有偏差的 dNTP 池、γ DNA 聚合酶错配以及不对称复制本身。他们中的大多数未能解释观察到的结果，水解脱氨是唯一与我们的数据一致的结果。因此，我们假设哺乳动物线粒体基因组不对称和有偏差的碱基组成起源的关键过程之一是复制过程中 H 链中 C 和 A 的自发脱氨基作用。
The base composition of 25 complete mammalian mitochondrial (mt) genomes has been analyzed taking into account all three codon positions (P-123) and fourfold degenerate sites (P-4FD) of H-strand genes. In the nontranscribed L strand, G is the less represented base and A is the most represented one in all cases, while C and T differ among species. H-strand protein-coding genes show an asymmetric distribution of the four bases between the two strands. The asymmetry indexes AT and GC skews on P-4FD are much higher than those on P-123, suggesting the existence of asymmetrical directional mutation pressure. Relationships between the compositional features and transcription or replication processes have been investigated in order to find a possible mechanism that could explain the origin of this asymmetry. AT and GC skews, the base composition in fourfold degenerate sites, and the number of variable sites for each gene are significantly correlated with the duration of single-stranded state of the H-stranded genes during replication. We tested different replication-related hypotheses, such as the existence of biased dNTP pools, gamma DNA polymerase mispairing, and the asymmetric replication itself. Most of them failed to explain the observed results, hydrolytic deaminations being the only one in agreement with our data. Thus, we hypothesize that one of the crucial processes for the origin of asymmetric and biased base composition of mammalian mitochondrial genomes is the spontaneous deamination of C and A in the H strand during replication.