Backward evolution from gene network dynamics

Abstract

Gene expression is controlled by regulator genes that together with effector genes form gene regulatory networks. How mutation in the genes comprising gene regulatory networks influences cell population dynamics has not been adequately investigated. In this study, we develop mathematical models to study how a mutation in a regulator gene that reaches the effector gene with a time delay affects short-term and long-term population growth. Using theory and experiment, we find a paradoxical outcome of evolution where a mutation in a regulator gene leads to an interaction between gene regulatory network and population dynamics, causing in certain cases a permanent decrease in population fitness in a constant environment.\n\nSignificance StatementThe properties of a cell are largely the products of its proteins, synthesized at rates depending on the regulation of protein coding genes. Single-cell measurements show that genetically identical cells can differ radically in their protein levels, partially due to the random production and degradation of proteins. It is currently unknown how mutants arise and spread in populations affected by such biological variability. We use computer simulations and evolution experiments to study how a mutant spreads in a population that carries a synthetic drug resistance gene network. Our results show for the first time a paradoxical outcome of evolution, where an initially beneficial mutation can interact with gene regulatory network dynamics and cause a permanent decrease in population fitness in the same environment.