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内容記述 |
This dissertation addresses the 4.9 kb (kilobases) nucleotide sequences of<br /> mitochondrial (mt) DNAs from five hominoid species (common and pygmy<br />chimpanzees, gorilla, orangutan and simang), and presents their detailed analyses,<br /> together with the known human whole sequence, to assess the tempo and mode of<br /> hominoid mtDNA evolution. Particular attention was paid to the rate of<br /> synonymous substitutions in protein coding region as well as of silent substitutions<br /> in other regions. This work was further extended to the whole mitochondrial<br /> genomes of four hominoid species (human, common chimpanzee,′ gorilla and<br /> orangutan) with additionally determined l0 to 12 kb mtDNAs from common<br /> chimpanzee, goriIIa and orangutan. These hominoid mtDNAs revealed several<br /> functionally and evolutionarily characteristic features and provided useful<br /> information on the history of hominoid species. <br /> Most significant observations drawn from the present data are summarized as<br /> follows. First, comparsion of the base compositions in any specified region of<br /> hominoid mtDNAs showed a strong base composition bias, as observed in other<br /> vertebrate mtDNAs. The L-stand of hominoid mtDNAs is rich in A (adenine) and<br /> C (cytosine) contents, but low in G (guanine) content. Base composition biases are<br /> strongest at the third codon positions and are evident along the whole genome,<br />independent of the genomic regions. Both codon usage and amino acid preference<br /> of mitochondrial protein genes are in agreement with the base composition biases.<br /> These observations suggested that there is a biased mutation pressure in mtDNA.<br /> A possible cause may be differential diaminations of C residues owing to the<br /> asymmetric replication of both L- and H-strands of mtDNA. It is possible that<br /> diffferential deamination has resulted in the reduced number of C residues in the H-<br />strand,although there has been no clear evidence for this possibility in hominoid<br /> mtDNAs.<br /> Second, there exist functionally important nucleotide sites over the genome.<br />Together with information on tertiary structures of proteins, as Well as on<br /> secondary structures of transfer (t) RNAs, ribosomal (r) RNA genes and noncoding<br /> regions, the distributjon of variable sites among hominoid mtDNAs suggested that<br /> some nucleotide sites have been playing important roles in peptide folding,<br /> assembly of proteins, or interaction to some other proteins and regulatory elements.<br /> Noteworthy are two functionally distinct regions in the maior noncoding region (D-<br />loop). One is concerned with promoter sequences for transcripdon and the other is<br /> with three conserved blocks. Oranguan mtDNA sequence revealed unusual<br /> substitutions at both of these regions. This suggested that the replication and<br /> transcription machinery in orangutan mtDNA may differ from that of other<br /> hominoid mtDNAs.<br /> Third, comparsion of nucleotide differences observed among closely related<br /> hominoids revealed a remarkably biased mode of changes. Between human and<br /> chimpanzee, 70% of the observed nuculeotide differences are silent changes that<br /> occur mostly in the small noncoding regions or at the third codon positions of<br /> protein genes. Extensive deletions and additions are observed, but they are found<br /> only in the noncoding regions. Such observations suggested a conserved mode of<br /> the evolution of hominoid mtDNA genomes. There is also a strong preference to<br /> transitions over transversions. Out of 852 variable third positions of codons<br /> between the human and common chimpanzee mtDNAs, 93% account for<br /> transitions of which 66% are TC transitions (in the L-strand). Within the<br /> remaming 7% transversions, CA differences are most frequent while GT are least.<br /> These substitution biases correlate well with biased base compositions, particularly<br /> the low G content of the L-strand. <br /> Fourth, owing to the outnumbered transitions and strong biases in the base<br /> compositions, synonymous substitutions reach rapidly a rather low saturation<br /> level. AG transitions attain a saturation level lower than TC transitions (in the L-<br />strand), and such a low ceiling is observed even between the human and<br /> chimpanzee pair that diverged around five million years ago. At present,it seems<br /> inevitable to select appropriate regions that have experienced theoretically tractable<br /> numbers of substitutions.In the case of hominoid mtDNAs, candidates are all types<br /> of changes in the tRNA and rRNA regions, transversions in the noncoding regions,<br /> and nonsynonymous changes and synonymous transversions in the protein coding<br /> regions.<br /> Fifth, rapidly evolving mtDNAs are potentially useful for addressing classical<br /> issues in taxonomy, provided that each nucletide site has not undergone extensive<br /> multiple-hit substitutions. From the Whole 16209 sites of mtDNAS compared<br /> among the four hominoid specles, it appears that 12137 such sites are suitable to<br /> phylogenetic use. The analysis strengthened the pattern and dating in hominoid<br /> diversifjcation infened from the Previous analysis of 4.9 kb reglon in six homjnoid<br /> species(among African apes,gorilla diverged first about 7.7 million years ago and<br /> then chimpanzee and human became distinct about 4.7 million years ago).<br /> Finally, the synonymous and nonsynonymous substitution rates were<br /> examined under the assumption of the gorilla divergence being 7.7 miIIion years<br />ago. The extent of the compositional biases differs from gene to gene. Such<br /> differences in base compositions, even if small, can bring about considerable<br />variations in observed synonymous differences, and may result in the region-<br />dependent estimate of the synonymous substitution rate. A care should be taken<br /> for heterogeneous transition and base composition biases as Well as different<br /> saturation levels of transition changes. The synonymous substitution rate<br />estimated with this caution showed the uniformity over genes (2.37 ± 0.11 x 10<sup>-8</sup> per<br /> site per year) and the high transition rate, about 17 times faster than the<br /> transversion rate. These synonymous and transition rates are comparable to the<br /> silent substitution rate in the noncoding segments dispersed between genes. On the<br /> other hand, the rate of nonsynonymous substitutions differs considerably from<br /> gene to gene as expected under the neutral theory of molecular evolution. The<br /> average differences in the gorilla - human and gorilla - chimpanzee comparisons<br /> indicated that the lowest rate is 0.7 x 10<sup>-9</sup> per site per year for <i>COI</i> and that the<br /> highest rate is 5.7 x 10<sup>-9</sup> for ATP<i>ase 8</i>. The degree of functional constraints<br /> (measured by the ratio of the nonsynonymous to the synonymous substitution rate)<br /> is 0.03 for COI and 0.24 for ATP<i>ase 8</i>. tRNA genes also showed variability in the<br /> base content and thus in the extent of nucleotide differences as well. The<br /> substitution rate averaged over 22 tRNAS is 5.6 x 10<sup>-9</sup> per site per year. The rate for<br /> 12<i>S</i> <i>r</i>RNA and 16<i>S</i> <i>r</i>RNA is 4.1 x 10<sup>-9</sup> and 6.9 x 10<sup>-9</sup> per site per year. respectively.<br /> All of these observations strongly suggested that mutations themselves occur more<br /> or less with the same rate and compositional biases. |
要旨・審査要旨 / Abstract, Screening Result (380.3 kB)
