Abstract
BackgroundGene duplication followed by the functional divergence of the resulting pair of paralogous proteins is a major force shaping molecular networks in living organisms. Recent species-wide data for protein-protein interactions and transcriptional regulations allow us to assess the effect of gene duplication on robustness and plasticity of these molecular networks.ResultsWe demonstrate that the transcriptional regulation of duplicated genes in baker's yeast Saccharomyces cerevisiae diverges fast so that on average they lose 3% of common transcription factors for every 1% divergence of their amino acid sequences. The set of protein-protein interaction partners of their protein products changes at a slower rate exhibiting a broad plateau for amino acid sequence similarity above 70%. The stability of functional roles of duplicated genes at such relatively low sequence similarity is further corroborated by their ability to substitute for each other in single gene knockout experiments in yeast and RNAi experiments in a nematode worm Caenorhabditis elegans. We also quantified the divergence rate of physical interaction neighborhoods of paralogous proteins in a bacterium Helicobacter pylori and a fly Drosophila melanogaster. However, in the absence of system-wide data on transcription factors' binding in these organisms we could not compare this rate to that of transcriptional regulation of duplicated genes.ConclusionsFor all molecular networks studied in this work we found that even the most distantly related paralogous proteins with amino acid sequence identities around 20% on average have more similar positions within a network than a randomly selected pair of proteins. For yeast we also found that the upstream regulation of genes evolves more rapidly than downstream functions of their protein products. This is in accordance with a view which puts regulatory changes as one of the main driving forces of the evolution. In this context a very important open question is to what extent our results obtained for homologous genes within a single species (paralogs) carries over to homologous proteins in different species (orthologs).
Highlights
Gene duplication followed by the functional divergence of the resulting pair of paralogous proteins is a major force shaping molecular networks in living organisms
While its manifestations both on the level of protein sequences and phenotypes are reasonably well documented, the data needed to quantify evolutionary changes taking place on the level of molecular networks have appeared only very recently. Systematic experiments such as high-throughput two hybrid assays of protein-protein interactions [3,4,6,7], chip-on-chip studies of wholegenome binding of a large number of transcription factors [2], and whole-genome assays of inactivations of single genes [5] or proteins [8] allowed us to go beyond describing particular cases of evolution of molecular networks and look at its large scale dynamics
For all molecular networks studied in this work we found that even the most distantly related paralogous proteins with amino acid sequence identities around 20% on average have more similar positions within a network than a randomly selected pair of proteins
Summary
Gene duplication followed by the functional divergence of the resulting pair of paralogous proteins is a major force shaping molecular networks in living organisms. We quantify this divergence in the baker's yeast Saccharomyces cerevisiae using several recent system-wide data sets To this end we measure: 1) The similarity of positions of duplicated genes in the transcription regulatory network [2] given by the number of transcription regulators that regulate both of them; 2) The similarity of the set of binding partners [3,4] of their protein products, and their ability to substitute for each other in knock-out experiments [5]. These measures reflect, correspondingly, the upstream and downstream properties of molecular networks around duplicated genes. We repeat this analysis using species-wide data on protein interaction networks in a bacterium Helicobacter pylori [6] and a fruit fly Drosophila melanogaster [7], as well as a systematic RNAi gene inactivation assay [8] in a nematode worm Caenorhabditis elegans
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