512 - Estimation of the Number of Nucleotide Substitutions...

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Estimation of the Number of Nucleotide Substitutions in the Control Region of Mitochondrial DNA in Humans and Chimpanzees Koichiro Tamura and Masatoshi Nei Department of Biology and Institute of Molecular Evolutionary Genetics, The Pennsylvania State University Examining the pattern of nucleotide substitution for the control region of mito- chondrial DNA ( mtDNA ) in humans and chimpanzees, we developed a new math- ematical method for estimating the number of transitional and transversional sub- stitutions per site, as well as the total number of nucleotide substitutions. In this method, excess transitions, unequal nucleotide frequencies, and variation of sub- stitution rate among different sites are all taken into account. Application of this method to human and chimpanzee data suggested that the transition / transversion ratio for the entire control region was - 15 and nearly the same for the two species. The 95% confidence interval of the age of the common ancestral mtDNA was estimated to be 80,000-480,000 years in humans and 0.57-2.72 Myr in common chimpanzees. Introduction The control region of mitochondrial DNA (mtDNA) in humans and apes is known to evolve very rapidly, and for this reason a number of authors (e.g., Horai and Hayasaka 1990; Vigilant et al. 199 1; Ward et al. 199 1) have used this region to study various problems of human evolution. However, the pattern of nucleotide sub- stitution in this region is quite complicated; the ratio of transitional to transversional nucleotide substitutions is very high (Brown et al. 1982; Aquadro and Greenberg 1983)) and the rate of nucleotide substitution (h) varies extensively among different sites ( Kocher and Wilson 199 1) . Furthermore, the transitional changes between purines and between pyrimidines do not occur with equal frequency, as will be seen later. Therefore, it is necessary to develop an appropriate mathematical method to use this region of mtDNA for the study of human evolution. The main purpose of this paper is to develop a mathematical method to estimate the number of nucleotide substitutions between sequences. However, before developing the mathematical method, we first investigate the pattern of nucleotide substitution in the control region of mtDNA in humans. We shall also apply the mathematical formula developed for estimating the number of nucleotide substitutions between humans and chimpanzees, as well as for the age of the common ancestral mtDNA in humans and chimpanzees. 1. Key words: mtDNA evolution, chimpanzees. control region, nucleotide substitutions, transition / transversion bias, human Address for correspondence and reprints: Masatoshi Nei, Institute of Molecular Evolutionary Genetics and Department of Biology, The Pennsylvania State University, 328 Mueller Laboratory, University Park, Pennsylvania 16802. Mol. Biol. Evol. 10(3):5 12-526. 1993.
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512 - Estimation of the Number of Nucleotide Substitutions...

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