Emergence and maintenance of functional modules in signaling pathways

Background: While detection and analysis of functional modules in biological systems have received great attention in recent years, we still lack a complete understanding of how such modules emerge. One theory is that systems must encounter a varying selection (i.e. environment) in order for modularity to emerge. Here, we provide an alternative and simpler explanation using a realistic model of biological signaling pathways and simulating their evolution. Results: These evolutionary simulations start with a homogenous population of a minimal pathway containing two effectors coupled to two signals via a single receptor. This population is allowed to evolve under a constant selection pressure for mediating two separate responses. Results of these evolutionary simulations show that under such a selective pressure, mutational processes easily lead to the emergence of pathways with two separate sub-pathways (i.e. modules) each mediating a distinct response only to one of the signals. Such functional modules are maintained as long as mutations leading to new interactions among existing proteins in the pathway are rare. Conclusion: While supporting a neutralistic view for the emergence of modularity in biological systems, these findings highlight the relevant rate of different mutational processes and the distribution of functional pathways in the topology space as key factors for its maintenance.