Polymorphic sites and the mechanism of evolution in human mitochondrial DNA.
Polymorphic sites and the mechanism of evolution in human mitochondrial DNA.
复制标题
DOI：
10.1093/genetics/106.3.479
复制
发表时间：
1984-03
期刊：
影响因子：
3.3
通讯作者：
R. Cann;W. Brown;A. Wilson
中科院分区：
文献类型：
--
作者：
R. Cann;W. Brown;A. Wilson
12种限制性内切酶被用于筛选来自四大洲的112个人的线粒体DNA中441个位点上是否存在切割位点。通过比较DNA片段大小与从一个人mtDNA的公布序列中预期的DNA片段大小，构建切割图。163个位点是多态的，即，存在于一些个体中，但不存在于其他个体中，278个位点不变。这些多态性可能是由单碱基取代引起的，并发生在基因组的所有功能区域。在77例病例中，可以确定突变的确切性质和位置（在限制性位点内），该突变导致已知人类mtDNA序列中缺乏限制性位点，而在另一个人类mtDNA中存在。在这77个增益突变中，有52个发生在编码蛋白质的基因中，34个是沉默的，18个引起氨基酸替换;此外，其中9个替换是激进的。值得注意的是，在已知的人类mtDNA序列和其他人类mtDNA之间，需要解释这77个限制性位点的差异，转换与颠换的异常比率也是如此。这一比例是低的限制性位点的大多数群体比已报道的序列比较有限的部分mtDNA基因组在密切相关的哺乳动物，也许表明一个特殊的功能作用或敏感性突变回文区含有高水平的鸟嘌呤和胞嘧啶。从163个多态性位点的基因组分布，可以推断，tRNA和rRNA基因的点突变变异水平几乎与蛋白质编码基因一样高，但低于非编码mtDNA。因此，对蛋白质合成装置的组件进行操作的功能约束对于线粒体可能比对于其他系统更低。此外，识别四个密码子的tRNA的线粒体基因比仅识别两个密码子的tRNA的线粒体基因更可变。在人类线粒体基因中，编码蛋白质的基因变异较大，其中之一是细胞色素氧化酶亚基2的基因;这种多肽在灵长类动物中的进化速度似乎比其他哺乳动物快5倍。细胞色素c是一种在电子传递中直接与氧化酶2亚基相互作用的细胞核编码蛋白质，在灵长类动物中的进化速度也比啮齿类动物或有蹄类动物快。这个例子，沿着线粒体rRNA基因和编码线粒体核糖体蛋白的核基因，为特定核基因和线粒体基因之间的协同进化提供了证据。
Twelve restriction enzymes were used to screen for the presence or absence of cleavage sites at 441 locations in the mitochondrial DNA of 112 humans from four continents. Cleavage maps were constructed by comparison of DNA fragment sizes with those expected from the published sequence for one human mtDNA. One hundred and sixty-three of the sites were polymorphic, i.e., present in some individuals but absent from others, 278 sites being invariant. These polymorphisms probably result from single base substitutions and occur in all functional regions of the genome.--In 77 cases, it was possible to specify the exact nature and location (within a restriction site) of the mutation responsible for the absence of a restriction site in a known human mtDNA sequence and its presence in another human mtDNA. Fifty-two of these 77 gain mutations occur in genes coding for proteins, 34 being silent and 18 causing amino acid replacements; moreover, nine of the replacements are radical.--Notable also is the anomalous ratio of transitions to transversions required to account for these 77 restriction site differences between the known human mtDNA sequences and other human mtDNAs. This ratio is lower for most groups of restriction sites than has been reported from sequence comparisons of limited parts of the mtDNA genome in closely related mammals, perhaps indicating a special functional role or sensitivity to mutagenesis for palindromic regions containing high levels of guanine and cytosine.--From the genomic distribution of the 163 polymorphic sites, it is inferred that the level of point mutational variability in tRNA and rRNA genes is nearly as high as in protein-coding genes but lower than in noncoding mtDNA. Thus, the functional constraints operating on components of the protein-synthetic apparatus may be lower for mitochondria than for other systems. Furthermore, the mitochondrial genes for tRNAs that recognize four codons are more variable than those recognizing only two codons.--Among the more variable of the human mitochondrial genes coding for proteins is that for subunit 2 of cytochrome oxidase; this polypeptide appears to have been evolving about five times faster in primates than in other mammals. Cytochrome c, a nuclearly encoded protein that interacts directly with the oxidase 2 subunit in electron transport, has also evolved faster in primates than in rodents or ungulates. This example, along with that for the mitochondrial rRNA genes and the nuclear genes coding for mitochondrial ribosomal proteins, provides evidence for coevolution between specific nuclear and mitochondrial genes.