Natural selection is a fundamental force shaping organismal evolution, as it both maintains function and enables adaptation and innovation. Viruses, with their typically short and largely coding genomes, experience strong and diverse selective forces, sometimes acting on timescales that can be directly measured. These selection pressures emerge from an antagonistic interplay between rapidly changing fitness requirements (immune and antiviral responses from hosts, transmission between hosts, or colonization of new host species) and functional imperatives (the ability to infect hosts or host cells and replicate within hosts). Indeed, computational methods to quantify these evolutionary forces using molecular sequence data were initially, dating back to the 1980s, applied to the study of viral pathogens. This preference largely emerged because the strong selective forces are easiest to detect in viruses, and, of course, viruses have clear biomedical relevance. Recent commoditization of affordable high-throughput sequencing has made it possible to generate truly massive genomic data sets, on which powerful and accurate methods can yield a very detailed depiction of when, where, and (sometimes) how viral pathogens respond to various selective forces.Here, we present recent statistical developments and state-of-the-art methods to identify and characterize these selection pressures from protein-coding sequence alignments and phylogenies. Methods described here can reveal critical information about various evolutionary regimes, including whole-gene selection, lineage-specific selection, and site-specific selection acting upon viral genomes, while accounting for confounding biological processes, such as recombination and variation in mutation rates.
Keywords: Codon models; Molecular evolution; Phylogenetics; Positive selection; Recombination; Relaxed selection; Virus evolution.