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An APOBEC3 molecular clock to estimate the date of emergence of hMPXV - Virological

Mary Wilson

Well-known member
August 6 2022

Áine O’Toole & Andrew Rambaut
Institute of Ecology and Evolution
University of Edinburgh
2022-06-05

We gratefully acknowledge the groups that have been publicly sharing MPXV genome sequence data which makes analyses such as this possible. These data are listed and cited in Table 1.

In a previous post we hypothesised that the current monkeypox virus (MPXV) epidemic had arisen from a non-human animal to human jump prior to 2017. This was based on the observation of a preponderance of a specific mode of mutation that is characteristic of cytosine deamination by molecules in the APOBEC3 family.

Here we show a linear accumulation of these mutation with time of collection of genome sequences, estimate the rate of accumulation and extrapolate back to estimate the time that these mutation started to accumulate. If we assume that APOBEC3-type mutations are indicative of replication within human cells and that all such mutations reconstructed in the phylogenetic tree of hMPXV1 genomes are the result of APOBEC3, then a simple extrapolation provides an estimate for the date of jump into the human population (Figure 1).

We estimate that APOBEC3-type mutations accumulate during human to human transmission at the rate of about 9 per year (8.74 with a 95% interval 7.34 – 10.15) which corresponds to an evolutionary rate of 4.43 × 10[SUP]-5[/SUP] substitutions per site per year (3.72 – 5.15 × 10[SUP]-5[/SUP]) for a genome length of 197,210 nucleotides. This rate is approximately 20-fold greater than the long term evolutionary rate estimated for MPXV in the non-human animal reservoir of 1.93 × 10[SUP]-6[/SUP] (95% highest posterior density interval 1.21–2.66 × 10[SUP]-6[/SUP]) (Patrono et al. 2020). ...

https://virological.org/t/an-apobec3...of-hmpxv/885/1
 
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