Research Interests

An important goal in molecular evolution is to illucidate how proteins evolved to perform their current biological functions, and to determine the mechanisms by which proteins diversify and co-evolve following gene duplication or speciation events. I study the evolution of endocrine signaling in metazoans using phylogenetics, ancestral protein reconstruction and tissue culture assays to explore the evolution of endocrine receptor/ hormone specificity. By combining gene family evolution with functional and manipulative experiments, I hope to reveal the mechanisms by which endocrine signaling complexes evolved, and learn more broadly about how new protein interactions are formed and maintained.

Selected Publications

Storz JF, Bridgham JT, Kelly SA, Garland T Jr. (2015) Genetic Approaches in Comparative and Evolutionary Physiology. Am J Physiol Regul Integr Comp Physiol, 309(3):R197-214.

McKeown AN*, Bridgham JT*, Anderson DW, Murphy MN, Ortlund EA, Thornton JW. (2014) Evolution of novel DNA specificity in steroid receptors: mechanisms for the emergence of a new regulatory module. Cell,159(1):58-68.

Bridgham JT, Keay J, Ortlund EA, Thornton JW. (2014) Vestigialization of an Allosteric Switch: Genetic and Structural Mechanisms for the Evolution of Constitutive Activity in a Steroid Receptor. PLoS Genetics, 10(1): e1004058.

Bridgham JT, Eick GN, Larroux C, Deshpande K, Harms, MJ, Gauthier MEA, Ortlund EA, Degnan BM, Thornton JW. (2010) Protein evolution by molecular tinkering: diversification of the nuclear receptor superfamily from a ligand-dependent ancestor. PLoS Biology, Oct 5;8(10). pii: e1000497.

Bridgham JT, Ortlund EA, Thornton JW. (2009) An epistatic ratchet constrains the direction of glucocorticoid receptor evolution. Nature, 461(7263): 515-519.

Bridgham JT, Brown JE, Rodriguez-Mari A, Catchen JM, Thornton JW. (2008) Evolution of a new function by degenerative mutation in cephalochordate steroid receptors. PloS Genet. 4(9): e1000191.

Ortlund EA*, Brigham JT*, Redinbo MR, Thorton JW. (2007) Crystal structure of an ancient protein: evolution by conformational epistasis. Science. 317(5844): 1544-1548.

Bridgham JT, Carroll SM, Thornton JW. (2006) Evolution of hormone-receptor complexity by molecular exploitation. Science. 312(5770): 97-101.