H. Akashi et Sw. Schaeffer, NATURAL-SELECTION AND THE FREQUENCY-DISTRIBUTIONS OF SILENT DNA POLYMORPHISM IN DROSOPHILA, Genetics, 146(1), 1997, pp. 295-307
In Escherichia coli, Saccharomyces cerevisiae, and Drosophila melanoga
ster, codon bias may be maintained by a balance among mutation pressur
e, genetic drift, and natural selection favoring translationally super
ior codons. Under such an evolutionary model, silent mutations fall in
to two fitness categories: preferred mutations that increase codon bia
s and unpreferred changes in the opposite direction. This prediction c
an be tested by comparing the frequency spectra of synonymous changes
segregating within populations; natural selection will elevate the fre
quencies of advantageous mutations relative to that of deleterious cha
nges. The frequency distributions of preferred and unpreferred mutatio
ns differ in the predicted direction among 99 alleles of two D. pseudo
obscura genes and five alleles of eight D. simulans genes. This result
confirms the existence of fitness classes of silent mutations. Maximu
m likelihood estimates suggest that selection intensity at silent site
s is, on average, very weak in both D. pseudoobscura and D. simulans (
\N(c)s\ approximate to 1). Inference of evolutionary processes from wi
thin-species sequence variation is often hindered by the assumption of
a stationary frequency distribution. This assumption can be avoided w
hen identifying the action of selection and tested when estimating sel
ection intensity.