Rate of sequence divergence under constant selection.
BACKGROUND
Divergence of two independently evolving sequences that originated from a common ancestor can be described by two parameters, the asymptotic level of divergence E and the rate r at which this level of divergence is approached. Constant negative selection impedes allele replacements and, therefore, is routinely assumed to decelerate sequence divergence. However, its impact on E and on r has not been formally investigated.


RESULTS
Strong selection that favors only one allele can make E arbitrarily small and r arbitrarily large. In contrast, in the case of 4 possible alleles and equal mutation rates, the lowest value of r, attained when two alleles confer equal fitnesses and the other two are strongly deleterious, is only two times lower than its value under selective neutrality.


CONCLUSIONS
Constant selection can strongly constrain the level of sequence divergence, but cannot reduce substantially the rate at which this level is approached. In particular, under any constant selection the divergence of sequences that accumulated one substitution per neutral site since their origin from the common ancestor must already constitute at least one half of the asymptotic divergence at sites under such selection.


METHODS
This article was reviewed by Drs. Nicolas Galtier, Sergei Maslov, and Nick Grishin.
Kondrashov
Alexey S
AS
Bioinformatics and Genomics Programme, Centre for Genomic Regulation, C/Dr Aiguader 88, Barcelona Biomedical Research Park Building, 08003 Barcelona, Spain.
Povolotskaya
Inna S
IS
Ivankov
Dmitry N
DN
Kondrashov
Fyodor A
FA
D000483:Alleles; D001483:Base Sequence; D056426:Genetic Loci / Q000235:genetics; D014644:Genetic Variation; D009154:Mutation / Q000235:genetics; D012641:Selection, Genetic