Host heterogeneity and epistasis explain punctuated evolution of SARS-CoV-2

Abstract

Identifying drivers of viral diversity is key to understanding the evolutionary as well as epidemiological dynamics of the COVID-19 pandemic. Using rich viral genomic data sets, we show that periods of steadily rising diversity have been punctuated by sudden, enormous increases followed by similarly abrupt collapses of diversity. We introduce a mechanistic model of saltational evolution with epistasis and demonstrate that these features parsimoniously account for the observed temporal dynamics of inter-genomic diversity. Our results provide support for recent proposals that saltational evolution may be a signature feature of SARS-CoV-2, allowing the pathogen to more readily evolve highly transmissible variants. These findings lend theoretical support to a heightened awareness of biological contexts where increased diversification may occur. They also underline the power of pathogen genomics and other surveillance streams in clarifying the phylodynamics of emerging and endemic infections. In public health terms, our results further underline the importance of equitable distribution of up-to-date vaccines.

Some mechanistic underpinnings of molecular adaptations of SARS-COV-2 spike protein by integrating candidate adaptive polymorphisms with protein dynamics

“…Long-ranged interactions between different sites within a given protein is critically important for protein function (Peters and Lively 1999; Bershtein et al 2006; Collins et al 2006; Ekeberg et al 2013; Levy et al 2017; Harrigan et al 2018; Otten et al 2018; Rojas Echenique et al 2019; Shimagaki and Weigt 2019; de la Paz et al 2020; Rizzato et al 2020; Yang et al 2020; Bisardi et al 2022) and for the CoV-2 S protein in particular (Zeng et al 2020; Castiglione et al 2021; Dong et al 2021; Garvin et al 2021; Nielsen et al 2022; Ramarao-Milne et al 2022; Rochman et al 2022; Rodriguez-Rivas et al 2022). By showing dynamic differences between the interactions of CAPs, which have likely played a major role in allowing the virus to infect human hosts, the binding site, and the characteristic mutations of dominant Delta and Omicron strains, we see a “fine-tuning” of protein behavior.…”

A laboratory framework for ongoing optimization of amplification-based genomic surveillance programs

“…The impact of viral divergence on amplicon sequencing performance was clearly demonstrated by a sharp reduction in genome sequencing coverage associated with the emergence of successive SARS-CoV-2 VOCs. The accumulation of genomic differences from wild-type SARS-CoV-2 to Alpha, from Alpha to Delta, and particularly from Delta to Omicron was indicative of saltational evolution within the viral population ( 26 ) and likely driven by persistent infections within susceptible immunocompromised hosts ( 27 ). Saltational events (i.e., large multi-mutational jumps resulting in distinct and distant variants) have been predominantly observed within the N-terminal domain and receptor-binding domain of the spike protein and were also considered a feature of emergent SARS-CoV-2 VOCs ( 28 ).…”

One Hundred Years of Influenza A Evolution

“…In practice, this means that the unrooted Hamming distibution can only be consistently generated using post-2008 data, due to the increased level of sequencing. In comparison, the unrooted Hamming distribution has been feasible for almost the entirety of the SARS-CoV-2 pandemic [32]. This highlights the value of extensive sequencing and how it enables new and qualitatively different analyses to be carried out.…”

“…The second type of visualization that we employ is the unrooted temporal Hamming distribution, as developed in [32]. As the name implies, there is no fixed reference sequence in this case.…”