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bioRxiv · 10.1101/2025.01.17.633662

A phylogenetic method identifies candidate drivers of the evolution of the SARS-CoV-2 mutation spectrum

Corbett-Detig, R.
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Abstract

The molecular processes that generate new mutations evolve, but the causal mechanisms are largely unknown. In particular, the relative rates of mutation types (e.g., C>T), the mutation spectrum, sometimes vary among closely related species and populations. I present an algorithm for subdividing a phylogeny into distinct mutation spectra. By applying this approach to a SARS-CoV-2 phylogeny comprising approximately eight million genome sequences, I identify 10 shifts in the mutation spectrum. I find strong enrichment consistent with candidate causal amino-acid substitutions in the SARS-CoV-2 polymerase, and strikingly three appearances of the same homoplasious substitution are each associated with decreased C>T relative mutation rates. With rapidly growing genomic datasets, this approach and future extensions promises new insights into the mechanisms of evolution of mutational processes.

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Corbett-Detig, R.. 2025-01-20. A phylogenetic method identifies candidate drivers of the evolution of the SARS-CoV-2 mutation spectrum. https://doi.org/10.1101/2025.01.17.633662

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