S6.3-1 Sunday, Jan. 5 13:30 Homeostasis and dynamic stability of the phenotype: Implications for understanding the nature and evolution of robustness and plasticity NIJHOUT, H.F.*; REED, M.C.; Duke University; Duke University email@example.com
Metabolic networks have evolved diverse and unusual homeostatic mechanisms that stabilize critical reactions against genetic and environmental variation. These mechanisms achieve stability dynamically, by continually altering some reaction rates in order to keep critical reactions stable. Thus phenotypic stability occurs far from the steady-state of the system. Robustness exists in only restricted regions of genotype space, and we show that natural standing genetic variation in human populations is concentrated in these regions. Thus homeostatic mechanisms allow the accumulation of small-effect and largely cryptic genetic variation that has a low correlation with the phenotype. The region of genotype space where the phenotype is stable is not a property of the topology of the network but is a function of both genotype and environment. Therefore, genetic perturbations and/or environmental shifts that disrupt the homeostatic regime can increase phenotypic variation and the correlation between standing genetic variation and phenotypic variation. We illustrate these various effects by means of well-validated mathematical models for one-carbon, dopamine, and serotonin metabolism. Robustness and stability are never perfect and, because they are maintained dynamically, can be readily perturbed. Falling off the tightrope between stability and change is easy and, through the release of genetic variation, may be an important enabler of rapid phenotypic evolution. Although we use examples from metabolic systems, where quantification of mechanism is particularly accessible, we note that the same principles obtain in other homeostatic systems in physiology and development.