77. RECONSIDERING THE VALIDITY OF TRANSCRIPTOME-WIDE ASSOCIATION STUDIES

Abstract

Fitness is an important parameter that quantifies the relative replicating capacity of a virus in a given environment. Fitness values depend on the environment in which the virus replicates, thus complicating fitness measurements in vivo because of the mosaic of changing environments in most infected hosts. Fitness landscapes, a pictorial representation of fitness values as a function of viral genomic sequences or environmental factors, is rugged for viruses, as supported by the effect of individual mutations and environmental modifications on virus replicative performance. One of the consequences of quasispecies dynamics is the presence of a molecular memory in virus populations consisting of genomes that were dominant at an earlier stage of the same evolutionary lineage. Memory levels are fitness-dependent and confer viral population preparedness to confront intermittent selective constraints. Epidemiological fitness recapitulates several factors that permit a virus type or variant to become dominant in the field. Fitness measurements are informative per se and to plan experiments to identify the molecular basis of an altered virus behavior.