Statistical Mechanics and Thermodynamics of Viral Evolution

This paper uses methods drawn from physics to study the life cycle of viruses. The paper analyzes a model of viral infection and evolution using the "grand canonical ensemble" and formalisms from statistical mechanics and thermodynamics. Using this approach we enumerate all possible genetic states of a model virus and host as a function of two independent pressures–immune response and system temperature. We prove the system has a real thermodynamic temperature, and discover a new phase transition between a positive temperature regime of normal replication and a negative temperature “disordered” phase of the virus. We distinguish this from previous observations of a phase transition that arises as a function of mutation rate. From an evolutionary biology point of view, at steady state the viruses naturally evolve to distinct quasispecies. This paper also reveals a universal relationship that relates the order parameter (as a measure of mutational robustness) to evolvability in agreement with recent experimental and theoretical work. Given that real viruses have finite length RNA segments that encode proteins which determine virus fitness, the approach used here could be refined to apply to real biological systems, perhaps providing insight into immune escape, the emergence of novel pathogens and other results of viral evolution.