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1.
Nuclear and mitochondrial genomes have to work in concert to generate a functional oxidative phosphorylation (OXPHOS) system. We have previously shown that we could restore partial OXPHOS function when chimpanzee or gorilla mitochondrial DNA (mtDNA) were introduced into human cells lacking mtDNA. However, we were unable to maintain orangutan mitochondrial DNA in a human cell. We have now produced chimpanzee, gorilla, orangutan, and baboon cells lacking mtDNA and attempted to introduce mtDNA from different apes into them. Surprisingly, we were able to maintain human mtDNA in an orangutan nuclear background, even though these cells showed severe OXPHOS abnormalities, including a complete absence of assembled ATP synthetase. Phylogenetic analysis of complex V mtDNA-encoded subunits showed that they are among the most evolutionarily divergent components of the mitochondrial genome between orangutan and the other apes. Our studies showed that adaptive coevolution of nuclear and mitochondrial components in apes can be fast and accelerate in recent branches of anthropoid primates.  相似文献   

2.
Nonneutral Mitochondrial DNA Variation in Humans and Chimpanzees   总被引:25,自引:4,他引:21       下载免费PDF全文
We sequenced the NADH dehydrogenase subunit 3 (ND3) gene from a sample of 61 humans, five common chimpanzees, and one gorilla to test whether patterns of mitochondrial DNA (mtDNA) variation are consistent with a neutral model of molecular evolution. Within humans and within chimpanzees, the ratio of replacement to silent nucleotide substitutions was higher than observed in comparisons between species, contrary to neutral expectations. To test the generality of this result, we reanalyzed published human RFLP data from the entire mitochondrial genome. Gains of restriction sites relative to a known human mtDNA sequence were used to infer unambiguous nucleotide substitutions. We also compared the complete mtDNA sequences of three humans. Both the RFLP data and the sequence data reveal a higher ratio of replacement to silent nucleotide substitutions within humans than is seen between species. This pattern is observed at most or all human mitochondrial genes and is inconsistent with a strictly neutral model. These data suggest that many mitochondrial protein polymorphisms are slightly deleterious, consistent with studies of human mitochondrial diseases.  相似文献   

3.
Restriction endonuclease fragments produced by EcoRI/AvaI or KpnI digestion and containing the small (12S) ribosomal RNA (rRNA) genes from the mitochondrial DNAs (mtDNAs) of the common chimpanzee, pygmy chimpanzee, gorilla, and orangutan were inserted into the plasmids pBR322 or pADD1. After species verification the inserted fragments were digested with SauIIIA, subcloned into M13mp7 vectors, and sequenced. The small rRNA gene sequences were compared with each other and with the published human sequence (Anderson et al. 1981). Substitutions were detected at 118 of the 955 nucleotide positions compared. Pairwise, the sequence differences ranged from 1% (between the chimpanzee species) to 9% (comparisons involving the orangutan); the proportion that were transitions ranged from 87% to 100%. Deletions and/or additions were noted at seven locations. With respect to evolutionary sequence lability, kinetic analysis indicated the presence of at least two classes of nucleotide positions; the more labile class occurs in sequences thought to form self-complementary duplexes (stems) in the mature rRNA. The high frequency of compensating substitutions, which maintain base-pairing within these sequences, corroborates their inferred structure. Phylogenetic inferences drawn from the sequence comparisons support the notion of an approximately equidistant relationship among chimpanzees, gorilla, and man, with the orangutan much less closely related. However, inference from a shared deletion suggests that the gorilla and the chimpanzees may be more closely related to one another than they are to man.  相似文献   

4.
Man's place in hominoidea revealed by mitochondrial DNA genealogy   总被引:7,自引:0,他引:7  
Summary Molecular biology has resurrected C. Darwin and T.H. Huxley's question about the origin of humans, but the precise branching pattern and dating remain controversial. To settle this issue, a large amount of sequence information is required. We determined mitochondrial (mt) DNA sequences for five hominoids; pygmy and common chimpanzees, gorilla, orangutan, and siamang. The common region compared with the known human sequence is 4759 by long, encompassing genes for 11 transfer RNAs and 6 proteins. Because of the high substitution rates in mammalian mtDNA and an unprecedentedly large region compared, the sequence differences clearly indicate that the closest relatives to human are chimpanzees rather than gorilla. For dating the divergences of human, chimpanzee, and gorilla, we used only unsaturated parts of sequence differences in which the mtDNA genealogy is not obscured by multiple substitutions. The result suggests that gorilla branched off 7.7 ± 0.7 million years (Myr) ago and human 4.7 ± 0.5 Myr ago; the time difference between these divergences being as long as 3 Myr.Offprint requests to: S. Horai  相似文献   

5.
Respiring mitochondria require many interactions between nuclear and mitochondrial genomes. Although mitochondrial DNA (mtDNA) from the gorilla and the chimpanzee are able to restore oxidative phosphorylation in a human cell, mtDNAs from more distant primate species are functionally incompatible with human nuclear genes. Using microcell-mediated chromosome and mitochondria transfer, we introduced and maintained a functional orangutan mtDNA in a human nuclear background. However, partial oxidative phosphorylation function was restored only in the presence of most orangutan chromosomes, suggesting that human oxidative phosphorylation-related nuclear-coded genes are not able to replace many orangutan ones. The respiratory capacity of these hybrids was decreased by 65%-80%, and cytochrome c oxidase (COX) activity was decreased by 85%-95%. The function of other respiratory complexes was not significantly altered. The translation of mtDNA-coded COX subunits was normal, but their steady-state levels were approximately 10% of normal ones. Nuclear-coded COX subunits were loosely associated with mitochondrial membranes, a characteristic of COX assembly-defective mutants. Our results suggest that many human nuclear-coded genes not only cannot replace the orangutan counterparts, but also exert a specific interference at the level of COX assembly. This cellular model underscores the precision of COX assembly in mammals and sheds light on the nature of nuclear-mtDNA coevolutionary constraints.  相似文献   

6.
Two mitochondrial DNA molecules which represent major Ovis aries mtDNA haplogroups were cloned and comparatively sequenced to assess the degree of intraspecific variation. A total of 9623 bp that correspond to 58% of both mitochondrial genomes were determined. The control region, the Cyt b , ND2, ND3, ND4L, COIII and 12 tRNA genes, including the origin of L-strand replication, were completely characterized. Partial sequence information was obtained from the 12S and 16S rRNA and an additional six protein coding and six tRNA genes. The control regions of the two mtDNAs showed a nucleotide divergence of 4·34% while coding regions differed by 0·44%. The number of sheep coding region substitutions was similar to values observed in intraspecific comparisons of mitochondrial DNAs that represent remote points in genealogical trees of mice and humans. However, replacement substitutions were only observed at ∼30% of the rate in mice and ∼20% of the rate in humans. Nucleotide substitutions with a potential for phenotypic effects were found in the 12S and 16S rRNA and in the ND1 and COIII genes.  相似文献   

7.
Hominoid phylogeny was investigated in terms of unique DNA sequence homologies. In comparisons from the human standpoint the ΔTe50 DNA values were Man 0, chimpanzee 0·7, gorilla 1·4, gibbon 2·7, orangutan 2·9, and African green monkey 5·7. In comparisons from the orangutan standpoint the ΔTe50 DNA values were orangutan 0, chimpanzee 1·8, Man 1·9, gorilla 2·3, gibbon 2·4 and African green monkey 4·3. These results indicate that chimpanzee and gorilla are cladistically closer to Man than to orangutan and other primates, and that gorilla DNA may have diverged slightly more from the ancestral state than chimpanzee or human DNA. Comparisons from chimpanzee and gorilla DNA standpoints are needed to achieve a more definitive picture of hominoid phylogeny.  相似文献   

8.
The nucleotide sequences of a segment of mitochondrial DNA (mtDNA) have been determined for nine species or subspecies of the subgenus Drosophila of the genus Drosophila. This segment contains two complete protein-coding genes (i.e., NADH dehydrogenase subunit 1 and cytochrome b) and a transfer RNA gene (tRNA(ser)). The G+C content at third-codon positions for the two protein-coding genes was 1.5 times higher than that in the D. melanogaster species group, which belongs to the subgenus Sophophora. However, there was a substantial difference between the nucleotide frequencies of G and C. The number of nucleotide substitutions per silent site was more than three times higher than that for nuclear DNA, although it was only 60% of that for mammalian mtDNA. Both parametric and nonparametric analyses revealed a strong transition-transversion bias in nucleotide substitution, as was observed in mammalian mtDNA. Moreover, the rate of substitution of A and T for G and C is higher than that for the opposite direction. This bias seems to be responsible for the extremely A+T-rich base composition of Drosophila mtDNA. It is also noted that the rate of transitional change between A and G is higher than that between T and C.  相似文献   

9.
Summary Segments of the Japanese quail mito-chondrial genome encompassing many tRNA and protein genes, the small and part of the large rRNA genes, and the control region have been cloned and sequenced. Analysis of the relative position of these genes confirmed that the tRNAGlu and ND6 genes in galliform mitochondrial DNA are located immediately adjacent to the control region of the molecule instead of between the cytochrome b and ND5 genes as in other vertebrates. Japanese quail and chicken display another distinctive characteristic, that is, they both lack an equivalent to the light-strand replication origin found between the tRNACys and tRNAAsn genes in all vertebrate mitochondrial genomes sequenced thus far. Comparison of the protein-encoding genes revealed that a great proportion of the substitutions are silent and involve mainly transitions. This bias toward transitions also occurs in the tRNA and rRNA genes but is not observed in the control region where transversions account for many of the substitutions. Sequence alignment indicated that the two avian control regions evolve mainly through base substitutions but are also characterized by the occurrence of a 57-bp deletion/addition event at their 5′ end. The overall sequence divergence between the two gallinaceous birds suggests that avian mitochondrial genomes evolve at a similar rate to other vertebrate mitochondrial DNAs.  相似文献   

10.
Numts are nonfunctional mitochondrial sequences that have translocated into nuclear DNA, where they evolve independently from the original mitochondrial DNA (mtDNA) sequence. Numts can be unintentionally amplified in addition to authentic mtDNA, complicating both the analysis and interpretation of mtDNA-based studies. Amplification of numts creates particular issues for studies on the noncoding, hypervariable 1 mtDNA region of gorillas. We provide data on putative numt sequences of the coding mitochondrial gene cytochrome oxidase subunit II (COII). Via polymerase chain reaction (PCR) and cloning, we obtained COII sequences for gorilla, orangutan, and human high-quality DNA and also from a gorilla fecal DNA sample. Both gorilla and orangutan samples yielded putative numt sequences. Phylogenetically more anciently transferred numts were amplified with a greater incidence from the gorilla fecal DNA sample than from the high-quality gorilla sample. Data on phylogenetically more recently transferred numts are equivocal. We further demonstrate the need for additional investigations into the use of mtDNA markers for noninvasively collected samples from gorillas and other primates.  相似文献   

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