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In gene regulatory circuits, the expression of individual genes is commonly modulated by a set of regulating gene products, which bind to a gene's cis-regulatory region. This region encodes an input-output function, referred to as signal-integration logic, that maps a specific combination of regulatory signals (inputs) to a particular expression state (output) of a gene. The space of all possible signal-integration functions is vast and the mapping from input to output is many-to-one: For the same set of inputs, many functions (genotypes) yield the same expression output (phenotype). Here, we exhaustively enumerate the set of signal-integration functions that yield identical gene expression patterns within a computational model of gene regulatory circuits. Our goal is to characterize the relationship between robustness and evolvability in the signal-integration space of regulatory circuits, and to understand how these properties vary between the genotypic and phenotypic scales. Among other results, we find that the distributions of genotypic robustness are skewed, so that the majority of signal-integration functions are robust to perturbation. We show that the connected set of genotypes that make up a given phenotype are constrained to specific regions of the space of all possible signal-integration functions, but that as the distance between genotypes increases, so does their capacity for unique innovations. In addition, we find that robust phenotypes are (i) evolvable, (ii) easily identified by random mutation, and (iii) mutationally biased toward other robust phenotypes. We explore the implications of these latter observations for mutation-based evolution by conducting random walks between randomly chosen source and target phenotypes. We demonstrate that the time required to identify the target phenotype is independent of the properties of the source phenotype. [ABSTRACT FROM AUTHOR]

In complex adaptive systems, the topological properties of the interaction network are strong governing influences on the rate of flow of information throughout the system. For example, in epidemiological models, the structure of the underlying contact network has a pronounced impact on the rate of spread of infectious disease throughout a population. Similarly, in evolutionary systems, the topology of potential mating interactions (i.e., population structure) affects the rate of flow of genetic information and therefore affects selective pressure. One commonly employed method for quantifying selective pressure in evolutionary algorithms is through the analysis of the dynamics with which a single favorable mutation spreads throughout the population (a.k.a. takeover time analysis). While models of takeover dynamics have been previously derived for several specific regular population structures, these models lack generality. In contrast, so-called pair approximations have been touted as a general technique for rapidly approximating the flow of information in spatially structured populations with a constant (or nearly constant) degree of nodal connectivities, such as in epidemiological and ecological studies. In this work, we reformulate takeover time analysis in terms of the well-known Susceptible-Infectious-Susceptible model of disease spread and adapt the pair approximation for takeover dynamics. Our results show that the pair approximation, as originally formulated, is insufficient for approximating pre-equibilibrium dynamics, since it does not properly account for the interaction between the size and shape of the local neighborhood and the population size. After parameterizing the pair approximation to account for these influences, we demonstrate that the resulting pair approximation can serve as a general and rapid approximator for takeover dynamics on a variety of spatially-explicit regular interaction topologies with varying population sizes and varying uptake and reversion probabilities. Strengths, limitations, and potential applications of the pair approximation to evolutionary computation are discussed. [ABSTRACT FROM AUTHOR]