Systems Biology of Phenotypic Robustness and Plasticity.
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SYNOPSIS: Gene regulatory networks, cellular biochemistry, tissue function, and whole body physiology are imbued with myriad overlapping and interacting homeostatic mechanisms that ensure that many phenotypes are robust to genetic and environmental variation. Animals also often have plastic responses to environmental variables, which means that many different phenotypes can correspond to a single genotype. Since natural selection acts on phenotypes, this raises the question of how selection can act on the genome if genotypes are decoupled from phenotypes by robustness and plasticity mechanisms. The answer can be found in the systems biology of the homeostatic mechanisms themselves. First, all such mechanisms operate over a limited range and outside that range the controlled variable changes rapidly allowing natural selection to act. Second, mutations and environmental stressors can disrupt homeostatic mechanisms, exposing cryptic genetic variation and allowing natural selection to act. We illustrate these ideas by examining the systems biology of four specific examples. We show how it is possible to analyze and visualize the roles of specific genes and specific polymorphisms in robustness in the context of large and realistic nonlinear systems. We also describe a new method, system population models, that allows one to connect causal dynamics to the variable outcomes that one sees in biological populations with large variation.
Published Version (Please cite this version)10.1093/icb/icx076
Publication InfoBest, J; Nijhout, HF; Reed, Michael C; & Sadre-Marandi, F (2017). Systems Biology of Phenotypic Robustness and Plasticity. Integr Comp Biol, 57(2). pp. 171-184. 10.1093/icb/icx076. Retrieved from http://hdl.handle.net/10161/15899.
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Professor of Mathematics
Professor Reed is engaged in a large number of research projects that involve the application of mathematics to questions in physiology and medicine. He also works on questions in analysis that are stimulated by biological questions. For recent work on cell metabolism and public health, go to firstname.lastname@example.org/metabolism. Since 2003, Professor Reed has worked with Professor Fred Nijhout (Duke Biology) to use mathematical methods to understan