Dynamics of gene circuits shapes evolvability

Jiménez, Alba; Cotterell, James; Munteanu, Andreea; Sharpe, James

doi:http://dx.doi.org/10.1073/pnas.1411065112

Dynamics of gene circuits shapes evolvability

Citation

Jiménez A, Cotterell J, Munteanu A, Sharpe J. Dynamics of gene circuits shapes evolvability. Proceedings of the National Academy of Sciences of the United States of America. 2015;112(7): 2103-8. DOI: 10.1073/pnas.1411065112

Abstract

To what extent does the dynamical mechanism producing a specific biological phenotype bias the ability to evolve into novel phenotypes? We use the interpretation of a morphogen gradient into a single stripe of gene expression as a model phenotype. Although there are thousands of three-gene circuit topologies that can robustly develop a stripe of gene expression, the vast majority of these circuits use one of just six fundamentally different dynamical mechanisms. Here we explore the potential for gene circuits that use each of these six mechanisms to evolve novel phenotypes such as multiple stripes, inverted stripes, and gradients of gene expression. Through a comprehensive and systematic analysis, we find that circuits that use alternative mechanisms differ in the likelihood of reaching novel phenotypes through mutation. We characterize the phenotypic transitions and identify key ingredients of the evolutionary potential, such as sensitive interactions and phenotypic hubs. Finally, we provide an intuitive understanding on how the modular design of a particular mechanism favors the access to novel phenotypes. Our work illustrates how the dynamical mechanism by which an organism develops constrains how it can evolve. It is striking that these dynamical mechanisms and their impact on evolvability can be observed even for such an apparently simple patterning task, performed by just three-node circuits.