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

ABSTRACT: 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.

SUBMITTER: Eames M

PROVIDER: S-EPMC2600897 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature

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

Eames Matt M Kortemme Tanja T

Structure (London, England : 1993) 20071101 11

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 ...[more]

PMID: 17997970

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Project description:BACKGROUND: Members of the forkhead gene family act as transcription regulators in biological processes including development and metabolism. The evolution of forkhead genes has not been widely examined and selection pressures at the molecular level influencing subfamily evolution and differentiation have not been explored. Here, in silico methods were used to examine selection pressures acting on the coding sequence of five multi-species FOX protein subfamily clusters; FoxA, FoxD, FoxI, FoxO and FoxP. RESULTS: Application of site models, which estimate overall selection pressures on individual codons throughout the phylogeny, showed that the amino acid changes observed were either neutral or under negative selection. Branch-site models, which allow estimated selection pressures along specified lineages to vary as compared to the remaining phylogeny, identified positive selection along branches leading to the FoxA3 and Protostomia clades in the FoxA cluster and the branch leading to the FoxO3 clade in the FoxO cluster. Residues that may differentiate paralogs were identified in the FoxA and FoxO clusters and residues that differentiate orthologs were identified in the FoxA cluster. Neutral amino acid changes were identified in the forkhead domain of the FoxA, FoxD and FoxP clusters while positive selection was identified in the forkhead domain of the Protostomia lineage of the FoxA cluster. A series of residues under strong negative selection adjacent to the N- and C-termini of the forkhead domain were identified in all clusters analyzed suggesting a new method for refinement of domain boundaries. Extrapolation of domains among cluster members in conjunction with selection pressure information allowed prediction of residue function in the FoxA, FoxO and FoxP clusters and exclusion of known domain function in residues of the FoxA and FoxI clusters. CONCLUSION: Consideration of selection pressures observed in conjunction with known functional information allowed prediction of residue function and refinement of domain boundaries. Identification of residues that differentiate orthologs and paralogs provided insight into the development and functional consequences of paralogs and forkhead subfamily composition differences among species. Overall we found that after gene duplication of forkhead family members, rapid differentiation and subsequent fixation of amino acid changes through negative selection has occurred.

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

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

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