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• W2011732085 abstract "Genetic and biochemical studies have revealed that the diversity of cell types and developmental patterns evident within the animal kingdom is generated by a handful of conserved, core modules. Core biological modules must be robust, able to maintain functionality despite perturbations, and yet sufficiently adaptable for random mutations to generate phenotypic variation during evolution. Understanding how robust, adaptable modules have influenced the evolution of eukaryotes will inform both evolutionary and synthetic biology. One such system is the MAP kinase module, which consists of a 3-tiered kinase circuit configuration that has been evolutionarily conserved from yeast to man. MAP kinase signal transduction pathways are used across eukaryotic phyla to drive biological functions that are crucial for life. Here we ask the fundamental question, why do MAPK modules follow a conserved 3-tiered topology rather than some other number? Using computational simulations, we identify a fundamental 2-tiered circuit topology that can be readily reconfigured by feedback loops and scaffolds to generate diverse signal outputs. When this 2-kinase circuit is connected to proximal input kinases, a 3-tiered modular configuration is created that is both robust and adaptable, providing a biological circuit that can regulate multiple phenotypes and maintain functionality in an uncertain world. We propose that the 3-tiered signal transduction module has been conserved through positive selection, because it facilitated the generation of phenotypic variation during eukaryotic evolution." @default.
• W2011732085 created "2016-06-24" @default.
• W2011732085 creator A5039097797 @default.
• W2011732085 creator A5077272790 @default.
• W2011732085 date "2014-06-19" @default.
• W2011732085 modified "2023-10-17" @default.
• W2011732085 title "How MAP kinase modules function as robust, yet adaptable, circuits" @default.
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• W2011732085 doi "https://doi.org/10.4161/cc.29349" @default.
• W2011732085 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4128883" @default.
• W2011732085 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25483189" @default.
• W2011732085 hasPublicationYear "2014" @default.
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