Abstract
The recent global outbreak of mpox, caused by monkeypox virus (MPV) emerged in Europe in 2022 and rapidly spread to over 40 countries. The Americas are currently facing the highest impact, reporting over 50,000 cases by early 2023. In this study, we analyzed 880 MPV isolates worldwide to gain insights into the evolutionary patterns and initial introduction events of the virus in Mexico. We found that MPV entered Mexico on multiple occasions, from the United Kingdom, Portugal, and Canada, and subsequently spread locally in different regions of Mexico. Additionally, we show that MPV has an open pangenome, highlighting the role of gene turnover in shaping its genomic diversity, rather than single-nucleotide polymorphisms (SNPs), which do not contribute significantly to genome diversity. Although the genome contains multiple SNPs in coding regions, these remain under purifying selection, suggesting their evolutionary conservation. One notable exception is amino acid position 63 of the protein encoded by the Cop-A4L gene, which is intricately related to viral maturity, which we found to be under strong positive selection. Ancestral state reconstruction indicated that the ancestral state at position 63 corresponds to the amino acid valine, which is present only in isolates of clade I. However, the isolates from the current outbreak contained threonine at position 63. Our findings contribute new information about the evolution of monkeypox virus.
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Gamaliel López-Leal thanks Paola Rojas-Estévez for her useful comments on the manuscript.
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705_2023_5936_MOESM2_ESM.pdf
Supporting information 2 Maximum-likelihood phylogenetic tree based on 880 MPV genome sequences. Clade I, clade IIa, and clade IIb are indicated by yellow, green, and blue branches, respectively. The lineage of each isolate is highlighted in different colors (ribbon color). Mexican isolates are indicated by red stars. The tree scale is based on the number of substitutions per site, and SH-aLRT support values ≥ 95 are depicted by strong red circles at the internal nodes of the phylogeny. (PDF 139 KB)
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Supporting information 4 Reconstruction of the ancestry of MPV. This figure shows a compressed visualization produced by PastML using a marginal posterior probability approximation (MPPA) with a model similar to F81. Different colors correspond to different geographic regions, namely, the ancestral node in red (United Kingdom) and the Mexican node in green. The numbers inside or next to the circles indicate the number of branches associated with specific nodes. The number of times that a branch appears in the same place indicates the number of times a particular substructure of the tree was found in the original phylogenetic tree. This indicates the number of independent introductions for that country, and dark gray indicates more than one branch at that position. This compression includes vertical and horizontal merging with optional relaxed merging and pruning to simplify complex tree representations, helping to highlight essential evolutionary patterns and reduce complexity. (PDF 31 KB)
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Supporting information 5 Table showing the number of shared genes (core genome) and total genes (pangenome) (DOCX 47 KB)
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Supporting information 7 Total number of sites under natural selection. The table shows the number of sites potentially under negative and positive selection in the MPV genome according to inference by the FEL method (see Materials and methods) (XLSX 37 KB)
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Gómez-Sánchez, I., Castelán-Sánchez, H.G., Martínez-Castilla, L.P. et al. Genetic insights into the microevolutionary dynamics and early introductions of human monkeypox virus in Mexico. Arch Virol 169, 2 (2024). https://doi.org/10.1007/s00705-023-05936-x
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DOI: https://doi.org/10.1007/s00705-023-05936-x