Cann R L, Brown W M, Wilson A C
Genetics. 1984 Mar;106(3):479-99. doi: 10.1093/genetics/106.3.479.
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.
使用12种限制性内切酶来筛查来自四大洲的112名人类线粒体DNA中441个位点是否存在切割位点。通过将DNA片段大小与已发表的一种人类线粒体DNA序列预期的片段大小进行比较，构建了切割图谱。其中163个位点是多态性的，即某些个体中存在而其他个体中不存在，278个位点是不变的。这些多态性可能是由单碱基替换导致的，并且出现在基因组的所有功能区域。——在77个案例中，有可能确定已知人类线粒体DNA序列中导致一个限制性内切酶位点缺失以及在另一个人类线粒体DNA中存在该位点的突变的确切性质和位置（在一个限制性位点内）。这77个获得性突变中有52个发生在编码蛋白质的基因中，34个是沉默突变，18个导致氨基酸替换；此外，其中9个替换是根本性的。——同样值得注意的是，为了解释已知人类线粒体DNA序列与其他人类线粒体DNA之间这77个限制性内切酶位点差异所需的转换与颠换的异常比例。对于大多数限制性内切酶位点组来说，这个比例低于从密切相关哺乳动物线粒体DNA基因组有限部分的序列比较中所报道的比例，这可能表明含有高水平鸟嘌呤和胞嘧啶的回文区域具有特殊的功能作用或对诱变的敏感性。——从163个多态性位点的基因组分布推断，tRNA和rRNA基因中的点突变变异性水平几乎与蛋白质编码基因中的一样高，但低于非编码线粒体DNA中的水平。因此，作用于线粒体蛋白质合成装置组件的功能限制可能比其他系统更低。此外，识别四个密码子的线粒体tRNA基因比只识别两个密码子的更具变异性。——在编码蛋白质的人类线粒体基因中，细胞色素氧化酶亚基2的基因变异性较高；在灵长类动物中，这条多肽的进化速度似乎比其他哺乳动物快约五倍。细胞色素c是一种由核基因编码的蛋白质，在电子传递中直接与氧化酶2亚基相互作用，在灵长类动物中的进化速度也比啮齿动物或有蹄类动物快。这个例子，连同线粒体rRNA基因和编码线粒体核糖体蛋白的核基因的例子，为特定核基因和线粒体基因之间的共同进化提供了证据。
