Shared quasispecies architecture in experimental and natural RNA virus populations

TL;DR

This study reveals that diverse RNA virus populations, including bacteriophage Qβ and SARS-CoV-2, share a common hierarchical genotype network architecture characterized by a central haplotype surrounded by layers of variants.

Contribution

It demonstrates that different RNA viruses exhibit a conserved genotype network structure, highlighting fundamental properties of sequence space influencing viral evolution.

Findings

Both viruses show a central dominant haplotype with surrounding variants.

Networks display hierarchical and topological similarities despite ecological differences.

Shared architecture suggests common principles in RNA virus population organization.

Abstract

RNA viruses form genetically diverse populations structured as mutant spectra, or quasispecies, whose internal organization influences their evolutionary and adaptive dynamics. While genetic diversity has been extensively characterized, the structural organization of viral populations in sequence space remains less explored. Here, we compare genotype network architectures in two RNA viruses with markedly different evolutionary contexts: bacteriophage $Q\beta$ evolving in controlled laboratory conditions and SARS-CoV-2 evolving within infected human hosts. Using deep sequencing data, we reconstruct the genotype network of mutationally coupled variants within viral populations and analyze their topological properties. Despite large differences in genome size, mutation rate, and ecological setting, both viruses exhibit a common organization: a highly abundant central haplotype surrounded by layers of variants of diminishing abundance as Hamming distance to the central haplotype increases. All reconstructed networks share qualitative and quantitative topological features, displaying a hierarchical structure. The robust organization of both populations under multiple conditions suggests that RNA viruses may share a common genotype network architecture governed by fundamental properties of sequence space and the generic mechanisms of replication and mutation. Genotype networks provide a unifying framework to describe viral population structure beyond conventional diversity measures and, by revealing how local constraints shape mutational search, offers insights into the predictability of viral evolution.