Molecular Biology and Evolution, Vol 16, 49-53, Copyright © 1999 by Society for Molecular Biology and Evolution
R Ophir, T Itoh, D Graur and T Gojobori
We propose a method by which the intensity of purifying selection on a
functional protein-coding gene is estimated by using three aligned
homologous sequences: a processed pseudogene (psi), a functional paralog
from the same species (g), and a functional ortholog from a different
species (o). For each such trio, we calculate the numbers of nucleotide
substitutions along the branches leading to psi and g, i.e., K psi and
K(g). If we assume that the mutation rates are the same in the genes and
the pseudogenes and that mutations occurring in a pseudogene do not affect
the fitness of the organism, we can show that the fraction of mutations
that are selectively neutral, fg, is equal to the ratio K(g)/K psi. Since
advantageous mutations occur only very rarely, such that they do not
contribute significantly to the rate of molecular evolution, the fraction
of deleterious mutations that are subject to purifying selection is 1-fg.
Therefore, the K(g)/K psi ratio can be used directly to estimate the
intensity of purifying selection, thereby isolating its effects on the rate
of evolution from those of mutation. We compared the selection intensities
of 12 orthologous protein-coding pairs from humans and murids. As expected,
the fraction of mutations that are subject to purifying selection is
strongest in the second codon position and weakest in the third.
Interestingly, the mean fractions of effectively neutral mutations in the
third codon position were only 41% and 42% for murids and humans,
respectively, indicating that many synonymous mutations are subject to
selective constraint. In several orthologous genes, we found that the
intensity of purifying selection is very different between murid and human
orthologous genes. There was no statistically significant difference in
overall intensity of purifying selection between humans and murids. Thus,
purifying selection does not seem to be an important factor contributing to
the observed differences in the rates of evolution between these two taxa.
ORIGINAL ARTICLE
A simple method for estimating the intensity of purifying selection in protein-coding genes
Department of Zoology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Israel.
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