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Much of our understanding of the molecular basis of endocrinology has been the product of highly productive studies that have focused on specific molecules (e.g., hormones) and their specific immediate interacting partners. However, biomolecules are not isolated particles, but instead they are elements of highly integrated interaction networks, and specific interactions among them drive virtually all cellular functions and underlie phenotypic complexity and diversity. Many hormones, and their specific receptors and other interacting proteins, are known to be evolutionarily related, which raises intriguing questions concerning how specificity originated within these systems. Our previous studies have illustrated that biochemical entities are developmentally and evolutionarily fluid, with capabilities to be altered both in composition and behavior. Gene birth and death are widespread phenomena in genome evolution and accounts for the great diversity of gene families involved in endocrinology. While concordance of evolutionary histories both in pattern and process of hormones, receptors and interacting proteins might be expected for integrated systems, studies have shown that the evolutionary history of receptors need not mirror that of their ligands. Simultaneous emergence, or loss, of multiple interacting partners by multiple gene duplication or gene loss is unlikely in evolution. Gene duplication is essential in the development of complex endocrinology. It is creative in producing elements that allow evolutionary tinkering and thus plays a major role in gene co-option (i.e., recruitment for novel functions) facilitating the evolution of greater biological complexity. Alternatively, if an interacting partner is lost, the retained partner may either be subsequently lost or, more interestingly, serve as raw material in evolution and become recruited into a new interaction yielding a new function. Thus, a stepwise process of elaboration through mutation and optimization ensues, adapting genes (and their encoded proteins) into the physiology of an organism. Here we review several recent advances in our understanding of the evolution of hormone signalling pathways that illustrate the power of an evolutionary perspective. Among our

The Power of an Evolutionary Perspective in Studies of Endocrinology