Developing an appropriate evolutionary baseline model for the study of human cytomegalovirus.

Human cytomegalovirus (HCMV) represents a major threat to human health, contributing to both birth defects in neonates as well as organ transplant failure and opportunistic infections in immunocompromised individuals. HCMV exhibits considerable inter- and intra-host diversity, which likely influences the pathogenicity of the virus. Therefore, understanding the relative contributions of various evolutionary forces in shaping patterns of variation is of critical importance both mechanistically as well as clinically. Herein we present the individual components of an evolutionary baseline model for HCMV, with a particular focus on congenital infections for the sake of illustration - including mutation and recombination rates, the distribution of fitness effects, infection dynamics, as well as compartmentalization - and describe the current state of knowledge of each. By building this baseline model, researchers will be able to better describe the range of possible evolutionary scenarios contributing to observed variation, as well as improve power and reduce false-positive rates when scanning for adaptive mutations in the HCMV genome.