Intrahost viral quasispecies, and their impact in epidemic and pandemic spread. (A) Schematic representation of mutant spectra. On the upper left, an infected individual is viewed as including multitudes of compartmentalized mutant distributions; in reality, they are of far larger population sizes than drawn in the picture for simplicity. On the right, genomes or subgenomic stretches are drawn as horizontal lines, and mutations are depicted as symbols on the lines. Assuming an average of five mutations per a 10,000 nt genome, the number of genomes without mutations is minimal; the number increases when shorter, subgenomic RNA stretches (length in nucleotides [nt] indicated in the upper boxes) are considered (lines not drawn to scale). The graphs below indicate the probability of occurrence of viral genomes with k mutations [p(k)] per genome or subgenomic RNA stretch (color code for RNA length in the inserted box), according to the Poisson distribution, assuming an average of five mutations per genome. A numerical example and the importance of the virus population size for exploration of the space of functionally relevant sequences are explained in the text. (B) Representation of the pandemic spread of a virus from infected to susceptible individuals. Mutant distributions, captured in population bottlenecks of different intensity (arrows), are the transmitted entities. The complexity of mutant spectra adds to the uncertainties inherent to modifications of virus behavior following expansions among susceptible individuals. For simplicity, in A and B we display only point mutations, but for some RNA viruses (particularly SARS-CoV-2), insertions, and more often deletions, also contribute to genomic and subgenomic RNA variations.
