Update to observations about putative APOBEC3 deaminase editing in the light of new genomes from USA

A brief update to this post: Initial observations about putative APOBEC3 deaminase editing driving short-term evolution of MPXV since 2017

Áine O’Toole & Andrew Rambaut
Institute of Ecology and Evolution
University of Edinburgh

Three genome sequences from the USA (two from 2022, one from 2021) have produced evidence of a new lineage clustering amongst the 2017 genomes. And another one from USA from 2021 splitting the long branch to the global 2022 lineage.

Figure 1 | Orange dots denote GAAA mutations, blue dots denote TCTT mutations (both predicted APOBEC3 dinucleotide mutations), cyan dots are other GA or CT mutations, and grey dots are other mutations.

All of these genomes exhibit the same pattern of having a predominance of likely APOBEC3 deaminase induced mutations.

A substantial number of the 2022 genomes have unique or shared APOBEC3 mutations confirming this mechanism as being the likely source of most genetic single nucleotide variation in humans within this lineage of MPXV.

If these APOBEC3 edits are specifically indicative of replication in humans as opposed to another host species then this would confirm this entire clade to be representative of the emergence of a human epidemic by 2017.

New USA genomes:

accession name reference
ON676708 MPXV_USA_2021_MD Gigante et al, 2022, CDC
ON674051 MPXV_USA_2022_FL001 Gigante et al, 2022, CDC
ON676707 MPXV_USA_2021_TX Gigante et al, 2022, CDC
ON675438 MPXV_USA_2022_VA001 Gigante et al, 2022, CDC