Protein coalitions in a core mammalian biochemical network linked by rapidly evolving proteins
1 Centre for Bioinformatics, Department of Informatics, School of Natural and Mathematical Sciences, King's College London, Strand, London WC2R 2LS, UK
2 Bioinformatics Group, MRC Harwell, Harwell Science and Innovation Campus, Oxfordshire OX11 0RD, UK
3 The Blavatnik School of Computer Sciences & Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel
4 Department of Biochemistry, University of Oxford, UK, South Parks Road, Oxford, OX1 3QU, UK
5 Institute of Cancer Research, Chester Beattie Laboratories, London SW3 6JB, UK
6 Computational Genomics Unit, Institute of Agrobiotechnology, Centre for Research & Technology Hellas (CERTH), GR-57001 Thessalonica, Greece
Citation and License
BMC Evolutionary Biology 2011, 11:142 doi:10.1186/1471-2148-11-142Published: 25 May 2011
Cellular ATP levels are generated by glucose-stimulated mitochondrial metabolism and determine metabolic responses, such as glucose-stimulated insulin secretion (GSIS) from the β-cells of pancreatic islets. We describe an analysis of the evolutionary processes affecting the core enzymes involved in glucose-stimulated insulin secretion in mammals. The proteins involved in this system belong to ancient enzymatic pathways: glycolysis, the TCA cycle and oxidative phosphorylation.
We identify two sets of proteins, or protein coalitions, in this group of 77 enzymes with distinct evolutionary patterns. Members of the glycolysis, TCA cycle, metabolite transport, pyruvate and NADH shuttles have low rates of protein sequence evolution, as inferred from a human-mouse comparison, and relatively high rates of evolutionary gene duplication. Respiratory chain and glutathione pathway proteins evolve faster, exhibiting lower rates of gene duplication. A small number of proteins in the system evolve significantly faster than co-pathway members and may serve as rapidly evolving adapters, linking groups of co-evolving genes.
Our results provide insights into the evolution of the involved proteins. We find evidence for two coalitions of proteins and the role of co-adaptation in protein evolution is identified and could be used in future research within a functional context.