Consensus-level substitution rates are distinct from the virion-level rate

Abstract

Estimating viral substitution rates is central to evolutionary epidemiology, and recent interest in within-host evolution has sharpened the question of what such rates measure. I distinguish two classes of evolutionary rate estimand that are rarely separated in phylogenetic analysis: the virion-level substitution rate (VLSR), a molecular quantity counting mutational events along lineages, and consensus-level substitution rates (CLSRs), population-summary quantities counting changes in the consensus sequences. CLSRs are indexed by the consensus-generation rule. The VLSR and CLSRs are both biologically meaningful, but not interchangeable. Because the consensus-generation rule defines a given CLSR, it should be a routine reporting requirement. This reflection should help analysts make more informed methodological choices when working with sets of virus sequences.