title: Constraint and contingency in multifunctional gene regulatory circuits.
abstract: Gene regulatory circuits drive the development, physiology, and behavior of organisms from bacteria to humans. The phenotypes or functions of such circuits are embodied in the gene expression patterns they form. Regulatory circuits are typically multifunctional, forming distinct gene expression patterns in different embryonic stages, tissues, or physiological states. Any one circuit with a single function can be realized by many different regulatory genotypes. Multifunctionality presumably constrains this number, but we do not know to what extent. We here exhaustively characterize a genotype space harboring millions of model regulatory circuits and all their possible functions. As a circuit's number of functions increases, the number of genotypes with a given number of functions decreases exponentially but can remain very large for a modest number of functions. However, the sets of circuits that can form any one set of functions becomes increasingly fragmented. As a result, historical contingency becomes widespread in circuits with many functions. Whether a circuit can acquire an additional function in the course of its evolution becomes increasingly dependent on the function it already has. Circuits with many functions also become increasingly brittle and sensitive to mutation. These observations are generic properties of a broad class of circuits and independent of any one circuit genotype or phenotype.
authors.affiliation: University of Zurich, Institute of Evolutionary Biology and Environmental Studies, Zurich, Switzerland.
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Payne
authors.forename: Andreas
authors.initials: A
authors.lastname: Wagner
mesh_terms: D015870:Gene Expression; D053263:Gene Regulatory Networks; D005838:Genotype; D006801:Humans; D008957:Models, Genetic