title: Evolutionary switches between two serine codon sets are driven by selection.
abstract: Serine is the only amino acid that is encoded by two disjoint codon sets so that a tandem substitution of two nucleotides is required to switch between the two sets. Previously published evidence suggests that, for the most evolutionarily conserved serines, the codon set switch occurs by simultaneous substitution of two nucleotides. Here we report a genome-wide reconstruction of the evolution of serine codons in triplets of closely related species from diverse prokaryotes and eukaryotes. The results indicate that the great majority of codon set switches proceed by two consecutive nucleotide substitutions, via a threonine or cysteine intermediate, and are driven by selection. These findings imply a strong pressure of purifying selection in protein evolution, which in the case of serine codon set switches occurs via an initial deleterious substitution quickly followed by a second, compensatory substitution. The result is frequent reversal of amino acid replacements and, at short evolutionary distances, pervasive homoplasy.
authors: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894.
authors: Igor B
authors: IB
authors: Rogozin
authors: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894.
authors: Frida
authors: F
authors: Belinky
authors: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894.
authors: Vladimir
authors: V
authors: Pavlenko
authors: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894.
authors: Svetlana A
authors: SA
authors: Shabalina
authors: Biomedical Engineering Department, University of Iowa, Iowa City, IA 52242.
authors: David M
authors: DM
authors: Kristensen
authors: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894; koonin@ncbi.nlm.nih.gov.
authors: Eugene V
authors: EV
authors: Koonin
mesh_terms: D000818:Animals; D001105:Archaea / Q000235:genetics; D001419:Bacteria / Q000235:genetics; D003062:Codon / Q000235:genetics*; D019143:Evolution, Molecular; D006801:Humans; D009154:Mutation; D012440:Saccharomyces / Q000235:genetics; D012641:Selection, Genetic; D012694:Serine / Q000235:genetics*
chemical_list: D003062:Codon; D012694:Serine
keywords: homoplasy; positive selection; purifying selection; serine codon sets; tandem nucleotide substitutions