title: Upstream plasticity and downstream robustness in evolution of molecular networks.
abstract: BACKGROUND
  Gene 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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  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. 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).
authors.affiliation: Department of Physics, Brookhaven National Laboratory, Upton, New York 11973, USA. maslov@bnl.gov
authors.forename: Sergei
authors.initials: S
authors.lastname: Maslov
authors.forename: Kim
authors.initials: K
authors.lastname: Sneppen
authors.forename: Kasper Astrup
authors.initials: KA
authors.lastname: Eriksen
authors.forename: Koon-Kiu
authors.initials: KK
authors.lastname: Yan
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D020440:Gene Duplication; D005786:Gene Expression Regulation; D020131:Genes, Duplicate / Q000235:genetics*; D014644:Genetic Variation; D016480:Helicobacter pylori / Q000235:genetics; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D012441:Saccharomyces cerevisiae / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D005656:Fungal Proteins; D015801:Helminth Proteins; D019476:Insect Proteins