title: From complete genomes to measures of substitution rate variability within and between proteins.
abstract: Accumulation of complete genome sequences of diverse organisms creates new possibilities for evolutionary inferences from whole-genome comparisons. In the present study, we analyze the distributions of substitution rates among proteins encoded in 19 complete genomes (the interprotein rate distribution). To estimate these rates, it is necessary to employ another fundamental distribution, that of the substitution rates among sites in proteins (the intraprotein distribution). Using two independent approaches, we show that intraprotein substitution rate variability appears to be significantly greater than generally accepted. This yields more realistic estimates of evolutionary distances from amino-acid sequences, which is critical for evolutionary-tree construction. We demonstrate that the interprotein rate distributions inferred from the genome-to-genome comparisons are similar to each other and can be approximated by a single distribution with a long exponential shoulder. This suggests that a generalized version of the molecular clock hypothesis may be valid on genome scale. We also use the scaling parameter of the obtained interprotein rate distribution to construct a rooted whole-genome phylogeny. The topology of the resulting tree is largely compatible with those of global rRNA-based trees and trees produced by other approaches to genome-wide comparison.
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894 USA. grishin@chop.swmed.edu
authors.forename: N V
authors.initials: NV
authors.lastname: Grishin
authors.forename: Y I
authors.initials: YI
authors.lastname: Wolf
authors.forename: E V
authors.initials: EV
authors.lastname: Koonin
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics*; D019295:Computational Biology; D019143:Evolution, Molecular; D014644:Genetic Variation / Q000235:genetics*; D016678:Genome; D008957:Models, Genetic; D015233:Models, Statistical; D010802:Phylogeny; D011506:Proteins / Q000235:genetics*; D016415:Sequence Alignment / Q000379:methods; D020539:Sequence Analysis, Protein / Q000379:methods
chemical_list: D011506:Proteins