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An improved method for determining codon variability in a gene and its application to the rate of fixation of mutations in evolution

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If one has the amino acid sequences of a set of homologous proteins as well as their phylogenetic relationships, one can easily determine the minimum number of mutations (nucleotide replacements) which must have been fixed in each codon since their common ancestor. It is found that for 29 species of cytochrome c the data fit the assumption that there is a group of approximately 32 invariant codons and that the remainder compose two Poisson-distributed groups of size 65 and 16 codons, the latter smaller group fixing mutations at about 3.2 times the rate of the larger. It is further found that the size of the invariant group increases as the range of species is narrowed. Extrapolation suggests that less than 10% of the codons in a given mammalian cytochrome c gene are capable of accepting a mutation. This is consistent with the view that at any one point in time only a very restricted number of positions can fix mutations but that as mutations are fixed the positions capable of accepting mutations also change so that examination of a wide range of species reveals a wide range of altered positions. We define this restricted group as the concomitantly variable codons. Given this restriction, the fixation rates for mutations in concomitantly variable codons in cytochrome c and fibrinopeptide A are not very different, a result which should be the case if most of these mutations are in fact selectively neutral as Kimura suggests.

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Paper number 1382 from the Laboratory of Genetics. Work performed in part at the University of Iowa, Department of Preventive Medicine and Environmental Health and Department of Statistics, Iowa City, Iowa. Computing supported by the Graduate College, University of Iowa.

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Fitch, W.M., Markowitz, E. An improved method for determining codon variability in a gene and its application to the rate of fixation of mutations in evolution. Biochem Genet 4, 579–593 (1970).

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