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Measuring the evolutionary rate of protein-protein interaction.

ABSTRACT: Despite our extensive knowledge about the rate of protein sequence evolution for thousands of genes in hundreds of species, the corresponding rate of protein function evolution is virtually unknown, especially at the genomic scale. This lack of knowledge is primarily because of the huge diversity in protein function and the consequent difficulty in gauging and comparing rates of protein function evolution. Nevertheless, most proteins function through interacting with other proteins, and protein-protein interaction (PPI) can be tested by standard assays. Thus, the rate of protein function evolution may be measured by the rate of PPI evolution. Here, we experimentally examine 87 potential interactions between Kluyveromyces waltii proteins, whose one to one orthologs in the related budding yeast Saccharomyces cerevisiae have been reported to interact. Combining our results with available data from other eukaryotes, we estimate that the evolutionary rate of protein interaction is (2.6 ± 1.6) × 10(-10) per PPI per year, which is three orders of magnitude lower than the rate of protein sequence evolution measured by the number of amino acid substitutions per protein per year. The extremely slow evolution of protein molecular function may account for the remarkable conservation of life at molecular and cellular levels and allow for studying the mechanistic basis of human disease in much simpler organisms.

SUBMITTER: Qian W

PROVIDER: S-EPMC3102417 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Measuring the evolutionary rate of protein-protein interaction.

Qian Wenfeng W He Xionglei X Chan Edwin E Xu Huailiang H Zhang Jianzhi J

Proceedings of the National Academy of Sciences of the United States of America 20110509 21

Despite our extensive knowledge about the rate of protein sequence evolution for thousands of genes in hundreds of species, the corresponding rate of protein function evolution is virtually unknown, especially at the genomic scale. This lack of knowledge is primarily because of the huge diversity in protein function and the consequent difficulty in gauging and comparing rates of protein function evolution. Nevertheless, most proteins function through interacting with other proteins, and protein- ...[more]

PMID: 21555556

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Project description:Rates of evolution differ widely among proteins, but the causes and consequences of such differences remain under debate. With the advent of high-throughput functional genomics, it is now possible to rigorously assess the genomic correlates of protein evolutionary rate. However, dissecting the correlations among evolutionary rate and these genomic features remains a major challenge. Here, we use an integrated probabilistic modeling approach to study genomic correlates of protein evolutionary rate in Saccharomyces cerevisiae. We measure and rank degrees of association between (i) an approximate measure of protein evolutionary rate with high genome coverage, and (ii) a diverse list of protein properties (sequence, structural, functional, network, and phenotypic). We observe, among many statistically significant correlations, that slowly evolving proteins tend to be regulated by more transcription factors, deficient in predicted structural disorder, involved in characteristic biological functions (such as translation), biased in amino acid composition, and are generally more abundant, more essential, and enriched for interaction partners. Many of these results are in agreement with recent studies. In addition, we assess information contribution of different subsets of these protein properties in the task of predicting slowly evolving proteins. We employ a logistic regression model on binned data that is able to account for intercorrelation, non-linearity, and heterogeneity within features. Our model considers features both individually and in natural ensembles ("meta-features") in order to assess joint information contribution and degree of contribution independence. Meta-features based on protein abundance and amino acid composition make strong, partially independent contributions to the task of predicting slowly evolving proteins; other meta-features make additional minor contributions. The combination of all meta-features yields predictions comparable to those based on paired species comparisons, and approaching the predictive limit of optimal lineage-insensitive features. Our integrated assessment framework can be readily extended to other correlational analyses at the genome scale.

Project description:BackgroundThe recently emerged protein interaction network paradigm can provide novel and important insights into the innerworkings of a cell. Yet, the heavy burden of both false positive and false negative protein-protein interaction data casts doubt on the broader usefulness of these interaction sets. Approaches focusing on one-protein-at-a-time have been powerfully employed to demonstrate the high degree of conservation of proteins participating in numerous interactions; here, we expand his 'node' focused paradigm to investigate the relative persistence of 'link' based evolutionary signals in a protein interaction network of S. cerevisiae and point out the value of this relatively untapped source of information.ResultsThe trend for highly connected proteins to be preferably conserved in evolution is stable, even in the context of tremendous noise in the underlying protein interactions as well as in the assignment of orthology among five higher eukaryotes. We find that local clustering around interactions correlates with preferred evolutionary conservation of the participating proteins; furthermore the correlation between high local clustering and evolutionary conservation is accompanied by a stable elevated degree of coexpression of the interacting proteins. We use this conserved interaction data, combined with P. falciparum/Yeast orthologs, as proof-of-principle that high-order network topology can be used comparatively to deduce local network structure in non-model organisms.ConclusionHigh local clustering is a criterion for the reliability of an interaction and coincides with preferred evolutionary conservation and significant coexpression. These strong and stable correlations indicate that evolutionary units go beyond a single protein to include the interactions among them. In particular, the stability of these signals in the face of extreme noise suggests that empirical protein interaction data can be integrated with orthologous clustering around these protein interactions to reliably infer local network structures in non-model organisms.

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Measuring the evolutionary rate of protein-protein interaction.

Publications

Measuring the evolutionary rate of protein-protein interaction.

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