Structural mapping of protein interactions reveals differences in evolutionary pressures correlated to mRNA level and protein abundance.

Genome-wide studies in Saccharomyces cerevisiae concluded that the dominant determinant of protein evolutionary rates is expression level: highly expressed proteins generally evolve most slowly. To determine how this constraint affects the evolution of protein interactions, we directly measure evolutionary rates of protein interface, surface, and core residues by structurally mapping domain interactions to yeast genomes. We find that mRNA level and protein abundance, though correlated, report on pressures affecting regions of proteins differently. Pressures proportional to mRNA level slow evolutionary rates of all structural regions and reduce the variability in rate differences between interfaces and other surfaces. In contrast, the evolutionary rate variation within a domain is much less correlated to protein abundance. Distinct pressures may be associated primarily with the cost (mRNA level) and functional (protein abundance) benefit of protein production. Interfaces of proteins with low mRNA levels may have higher evolutionary flexibility and could constitute the raw material for new functions.

[1]  E. O’Shea,et al.  Global analysis of protein expression in yeast , 2003, Nature.

[2]  Wei-Lun Hsu,et al.  Proportion of solvent-exposed amino acids in a protein and rate of protein evolution. , 2007, Molecular biology and evolution.

[3]  M. Gerstein,et al.  Annotation transfer between genomes: protein-protein interologs and protein-DNA regulogs. , 2004, Genome research.

[4]  R. Nussinov,et al.  Conservation of polar residues as hot spots at protein interfaces , 2000, Proteins.

[5]  C. Wilke,et al.  A single determinant dominates the rate of yeast protein evolution. , 2006, Molecular biology and evolution.

[6]  J. L. King,et al.  Non-Darwinian evolution. , 1969, Science.

[7]  C. Pál,et al.  An integrated view of protein evolution , 2006, Nature Reviews Genetics.

[8]  C. Pál,et al.  Highly expressed genes in yeast evolve slowly. , 2001, Genetics.

[9]  Philip M. Kim,et al.  Relating Three-Dimensional Structures to Protein Networks Provides Evolutionary Insights , 2006, Science.

[10]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[11]  Robert B. Russell,et al.  3did: interacting protein domains of known three-dimensional structure , 2004, Nucleic Acids Res..

[12]  C. Wilke,et al.  Why highly expressed proteins evolve slowly. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[13]  S. Vajda,et al.  Anchor residues in protein-protein interactions. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[14]  A. E. Hirsh,et al.  Evolutionary Rate in the Protein Interaction Network , 2002, Science.

[15]  T. Ohta.  Slightly Deleterious Mutant Substitutions in Evolution , 1973, Nature.

[16]  Ross Ihaka,et al.  Gentleman R: R: A language for data analysis and graphics , 1996 .

[17]  Frances H Arnold,et al.  Structural determinants of the rate of protein evolution in yeast. , 2006, Molecular biology and evolution.

[18]  Daniel R. Caffrey,et al.  Are protein–protein interfaces more conserved in sequence than the rest of the protein surface? , 2004, Protein science : a publication of the Protein Society.

[19]  Dennis P Wall,et al.  A simple dependence between protein evolution rate and the number of protein-protein interactions , 2003, BMC Evolutionary Biology.

[20]  M. Gerstein,et al.  Comparing protein abundance and mRNA expression levels on a genomic scale , 2003, Genome Biology.

[21]  M. Kimura.  Evolutionary Rate at the Molecular Level , 1968, Nature.

[22]  J. Thornton,et al.  Structural characterisation and functional significance of transient protein-protein interactions. , 2003, Journal of molecular biology.

[23]  E. Vallender,et al.  Systematically assessing the influence of 3-dimensional structural context on the molecular evolution of mammalian proteomes. , 2006, Molecular biology and evolution.

[24]  Robert D. Finn,et al.  Pfam: clans, web tools and services , 2005, Nucleic Acids Res..

[25]  C. Adami,et al.  Apparent dependence of protein evolutionary rate on number of interactions is linked to biases in protein–protein interactions data sets , 2003, BMC Evolutionary Biology.

[26]  Z. Weng,et al.  Structure, function, and evolution of transient and obligate protein-protein interactions. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[27]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[28]  Christoph Adami,et al.  Evolutionary rate depends on number of protein-protein interactions independently of gene expression level: Response , 2004, BMC Evolutionary Biology.

[29]  S. Teichmann.  The constraints protein-protein interactions place on sequence divergence. , 2002, Journal of molecular biology.

[30]  Ziheng Yang,et al.  PAML: a program package for phylogenetic analysis by maximum likelihood , 1997, Comput. Appl. Biosci..

[31]  R. Russell,et al.  The relationship between sequence and interaction divergence in proteins. , 2003, Journal of molecular biology.

[32]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.