Abstract
BackgroundCellular 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.ResultsWe 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.ConclusionsOur 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.
Highlights
Cellular ATP levels are generated by glucose-stimulated mitochondrial metabolism and determine metabolic responses, such as glucose-stimulated insulin secretion (GSIS) from the b-cells of pancreatic islets
Glucose-stimulated insulin secretion (GSIS) from the b-cells of pancreatic islets is a metabolic response that is critically dependent on cellular ATP levels generated by glucose-stimulated mitochondrial metabolism
The soluble enzymes carrying out core metabolic processes, glycolysis and the TCA cycle, evolve slowly at the sequence level but undergo a relatively high rate of gene duplication compared to the respiratory chain and glutathione pathway proteins, which evolve more rapidly but undergo relatively little gene duplication
Summary
Cellular ATP levels are generated by glucose-stimulated mitochondrial metabolism and determine metabolic responses, such as glucose-stimulated insulin secretion (GSIS) from the b-cells of pancreatic islets. Eukaryotic organisms make use of complex biochemical pathways to maintain homeostatic processes in response to changes in their environment. These responses can be broadly divided into gene regulatory responses, whereby changes in an environmental condition give rise to changes in gene expression, and metabolic responses, which result from the responses of metabolic networks to environmental changes. Many of the components in this biochemical network are ancient enzymes with evolutionary origins in bacteria and predate the invention of pancreatic b-cells. We consider the evolution of the components of this system as an example of an element of core cellular biochemistry that is used for a cell-typespecific function
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