The influence of selection on the evolutionary distance estimated from thebase changes observed between homologous nucleotide sequences

Otsuka, J Kawai, Y Sugaya, N

J. Otsuka et al., The influence of selection on the evolutionary distance estimated from thebase changes observed between homologous nucleotide sequences, J THEOR BIO, 213(2), 2001, pp. 129-144

53

INGLESE

Article

Multidisciplinary

JOURNAL OF THEORETICAL BIOLOGY

0022-5193 → ACNP

213

2

2001

129 - 144

ISI

0022-5193(20011121)213:2<129:TIOSOT>2.0.ZU;2-K

In most studies of molecular evolution, the nucleotide base at a site is as sumed to change with the apparent rate under functional constraint, and the comparison of base changes between homologous genes is thought to yield th e evolutionary distance corresponding to the site-average change rate multi plied by the divergence time. However, this view is not sufficiently succes sful in estimating the divergence time of species, but mostly results in th e construction of tree topology without a time-scale. In the present paper, this problem is investigated theoretically by considering that observed ba se changes are the results of comparing the survivals through selection of mutated bases. In the case of weak selection, the time course of base chang es due to mutation and selection can be obtained analytically, leading to a theoretical equation showing how the selection has influence on the evolut ionary distance estimated from the enumeration of base changes. This result provides a new method for estimating the divergence time more accurately f rom the observed base changes by evaluating both the strength of selection and the mutation rate. The validity of this method is verified by analysing the base changes observed at the third codon positions of amino acid resid ues with four-fold codon degeneracy in the protein genes of mammalian mitoc hondria; i.e. the ratios of estimated divergence times are fairly well cons istent with a series of fossil records of mammals. Throughout this analysis , it is also suggested that the mutation rates in mitochondrial genomes are almost the same in different lineages of mammals and that the lineage-spec ific base-change rates indicated previously are due to the selection probab ly arising from the preference of transfer RNAs to codons. (C) 2001 Academi c Press.