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Unformatted text preview: ce interval of the average number of substitutions becomes d + 2 SE = 0.304-l .200. Therefore, the 95%-confidence upper and lower bounds of the average rate of substitution per site per year per lineage (h) are 2.5 X lop8 and 1.5 X 10m7, respectively. On the other hand, if we use a divergence time of 5 Myr between humans and chimpanzees, without considering the SE of 2, . the rate becomes 7.5 X 10 -‘ We call this the “modal rate” in the following. In table 4, we have seen that the $ for the deepest root of human mtDNA sequences is 0.024. Therefore, the 95%-confidence upper and lower bounds of the age of the common ancestral mtDNA (d/2X) become 80,000 and 480,000 years, respectively, whereas the age when the modal rate is used is 160,000 years. (Here we have ignored the SE of a for the deepest root, because the error for the substitution rate h has already been considered, and this error is not independent of the error of 2.) The 95% confidence interval of the age is similar to that obtained by Nei ( 1992) by a different method, but the range of the estimate is considerably wider than that given by Vigilant et al. ( 199 1) . This is because Vigilant et al. did not consider the SEs of their estimates. The mtDNAs in common chimpanzees are known to be more variable than those in humans (Ferris et al. 198 1; Kocher and Wilson 199 1 ), but no one seems to have estimated the age of the common ancestral mtDNA. Although there are only three sequences for the mtDNA control region, it is interesting to estimate this age, because it is apparently much older than that of humans. For this purpose, we constructed a neighbor-joining tree for the three sequences, using the pygmy chimpanzee as an outgroup. The results obtained are presented in figure 2. From this figure, we can compute the d for the common ancestor of the three sequences by taking the average of d’ for C 1 versus C2 and Cl versus C3. It becomes 0.136. Therefore, if we s use the modal rate, the age of the common ancestral mtDNA becomes 0.9 Myr. If we consider the 95% confidence interval, the age is estimated to be 0.57-2.72 Myr. These values are approximately six times higher than those for humans. These are minimum estimates, because only three sequences are used. r I -%c3 c2 ICl
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FIG. 2.-Phylogenetic tree for three common (C) and one pygmy (P) chimpanzee sequences of the mtDNA control region. This tree was constructed by the neighbor-joining method, from the distances computed by equation ( 15) . Nucleotide Substitution in mtDNA 523 Discussion It is well known that the rate of nucleotide (or amino acid) substitution generally varies extensively with nucleotide (or amino acid) site (Fitch and Margoliash 1967; Uzzell and Corbin 197 1; Shoemaker and Fitch 1989). A simple method to estimate the total number of nucleotide substitutions in this case is to assume that there are two classes of sites and that the sites in the first class are invariable whereas those in the second class are subject to substitution with the same rate (Fitch and Margoliash 1967; Hasegawa et al. 1985 ) . In practice, however, this model is less realistic than the one developed in the present paper, because variation in substitution rate is usually continuous (Uzzell and Corbin 197 1; Kocher and Wilson 199 1) . This is clearly the case with the mtDNA control region (table 2). Actually, Wakeley (submitted) showed that, in the 250-bp 5’ -side hypervariable segment of this region, even a model of two different rate classes does not fit the data, while the negative binomial distribution fits very well. Hasegawa and Horai ( 199 1) fitted the above two-class model to human and chimpanze...
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This note was uploaded on 01/06/2010 for the course NS 2750 taught by Professor Haas&gu during the Spring '08 term at Cornell.
- Spring '08