The role of APOBEC3-induced mutations in the differential evolution of monkeypox virus

TL;DR

This paper investigates how APOBEC3-induced mutations influence the evolution of monkeypox virus, developing a new statistical method to distinguish these mutations from genetic drift.

Contribution

It introduces a generalized GTR model-based method to identify APOBEC3 editing signatures and infer evolutionary lineage and events in MPXV.

Findings

APOBEC3-induced mutations are likely responsible for observed SNPs

The method can distinguish editing from genetic drift

Lineage information and evolutionary events can be estimated

Abstract

Recent studies show that newly sampled monkeypox virus (MPXV) genomes exhibit mutations consistent with Apolipoprotein B mRNA Editing Catalytic Polypeptide-like3 (APOBEC3)-mediated editing, compared to MPXV genomes collected earlier. It is unclear whether these single nucleotide polymorphisms (SNPs) result from APOBEC3-induced editing or are a consequence of genetic drift within one or more MPXV animal reservoirs. We develop a simple method based on a generalization of the General-Time-Reversible (GTR) model to show that the observed SNPs are likely the result of APOBEC3-induced editing. The statistical features allow us to extract lineage information and estimate evolutionary events.