Selection analysis identifies significant mutational changes in Omicron

CIDRI-Africa investigators have contributed to a post on the discussion forum "Virological" titled "Selection analysis identifies significant mutational changes in Omicron that are likely to influence both antibody neutralization and Spike function". 

"The Omicron (B.1.1.529) SARS-CoV-2 variant of concern (VOC) identified in Southern Africa in late November 2021 is the product of extensive evolution within an infection context that has so far left no obvious traces of intermediate forms since it diverged from the B.1.1 lineage (presumably at some time in mid to late 2020). Three possible explanations for the missing intermediates are: (1) SARS-CoV-2 sampling in Southern Africa between May and September 2021 might have been too sparse or biased to detect low frequency variants amongst high numbers of Delta variant infections during this time period; (2) long-term evolution in one or more chronically infected people - similar to the proposed origin of lineages such as Alpha and C.1.2 (1) 5 (2) 2 (3) 1 - where intermediate forms would have remained unsampled within the individual(s); and (3) a reverse zoonosis to a non-human host, followed by undetected spread therein, and a spillover back into humans. At present there is no direct evidence to support or reject any of these hypotheses on the origin of Omicron, but as new data are collected, its origin may be more precisely identified.

Regardless of the route that Omicron took to eventual community transmission, its genome accumulated 53 mutations relative to the Wuhan-Hu-1 reference strain, with 30 non-synonymous substitutions in the Spike encoding S gene alone. Here, we characterize the selective pressures that may have acted during the genesis of the Omicron variant and curate available phenotypic and genomic variation data associated with Omicron mutations. We are particularly interested in comparing evolutionary patterns at sites where Omicron has differences from the Wuhan-Hu-1 reference genome, most other SARS-CoV-2 lineages (including variation of SARS-CoV-2 in individual hosts), and closely related non-human sarbecoviruses. We use these comparisons to identify which Omicron mutations might contribute to transmission advantages, immune escape, or novel spike functionality. Our analysis identifies three clustered sets of mutations in the Spike protein, involving 13 amino acids that have previously been highly conserved across SARS-CoV-2 and other Sarbecoviruses. This dramatic about-face in evolutionary dynamics at these 13 sites suggests that Omicron’s Spike protein structure has accommodated significant sequence change, likely in response to selective pressures favoring increased transmission,immune evasion, or viral replication—either at the population level or in a single or group of chronically infected individuals—and has potentially acquired new functionality." (Source: Selection analysis identifies significant mutational changes in Omicron that are likely to influence both antibody neutralization and Spike function (Part 1 of 2) - SARS-CoV-2 coronavirus - Virological. https://virological.org/t/selection-analysis-identifies-significant-mutational-changes-in-omicron-that-are-likely-to-influence-both-antibody-neutralization-and-spike-function-part-1-of-2/771 (accessed Dec 6, 2021)). Join the discussion here.