{
  "abstract": "The 2022 global mpox outbreak was characterized by an unusual accumulation of more than fifty APOBEC-signature substitutions in MPXV genomes. A previous study suggested that these substitutions preferentially occur within and near hairpins or cruciforms - stem-loop structures formed by inverted repeats. Here, we show that this conclusion resulted from an inappropriate statistical analysis and, using two substantially larger datasets, demonstrate that APOBEC-signature mutations are specifically enriched at TC motifs located at the 3' ends of hairpin loops, but not in other regions of hairpins/cruciforms or in their vicinity. We further identified a preference for stem-loop structures with longer stems and shorter loops, consistent with patterns previously reported for the APOBEC mutagenesis in cancer genomes. Our analysis also revealed a positive association between APOBEC-signature mutation propensity and hairpin stability in single-stranded DNA. Nevertheless, stem-loop structures with long stems and short loops are relatively rare in the MPXV genome, limiting their contribution to the genome-wide distribution of APOBEC-signature mutations to a predominantly local effect. In contrast, extended nucleotide context downstream of the TC motif showed strong genome-wide predictive value, with a marked preference for guanine-rich trinucleotide immediately downstream. Analysis of the upstream nucleotide context was consistent with the mutational specificity of APOBEC3A. Together, these results identify distinct structural and sequence determinants of the APOBEC-associated mutagenesis in MPXV and show that local hairpin/cruciform architecture and extended nucleotide context contribute at different genomic scales.",
  "abstract_shown": true,
  "affiliations": [
    "Vavilov Institute of General Genetics, Moscow, Russia"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "name": "A. V. Madorskaya"
    },
    {
      "affs": [
        0
      ],
      "name": "F. M. Kazanov"
    },
    {
      "name": "D. A. Bogdanov"
    },
    {
      "name": "G. V. Ponomarev"
    },
    {
      "name": "A. E. Smolnikova"
    },
    {
      "name": "D. V. Garshina"
    },
    {
      "name": "E. V. Matveev"
    },
    {
      "name": "R. K. Abasov"
    },
    {
      "name": "C. Azgari"
    },
    {
      "name": "O. D. Adebali"
    },
    {
      "name": "D. N. Ivankov"
    },
    {
      "name": "M. S. Gelfand"
    },
    {
      "affs": [
        0
      ],
      "name": "M. D. Kazanov"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/184zhp98vst6c.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.03.756454",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.03.756454v1.full",
  "id": "184zhp98vst6c",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.03.756454v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "microbiology"
    ],
    [
      "openalex",
      "2406|Poxvirus research and outbreaks"
    ]
  ],
  "openalex": "W7220675914",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.03.756454v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-03",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/184zhp98vst6c.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:16Z",
      "native_id": "10.64898/2026.10.03.756454",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.03.756454v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:microbiology",
      "subfield": "microbiology"
    }
  ],
  "title": "Hairpin Architecture and Extended Sequence Context Shape APOBEC3 Mutagenesis in Monkeypox Virus at Different Genomic Scales",
  "title_text": "Hairpin Architecture and Extended Sequence Context Shape APOBEC3 Mutagenesis in Monkeypox Virus at Different Genomic Scales",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:16Z",
  "url": "https://research.draconitic.com/paper/184zhp98vst6c",
  "venue": "bioRxiv",
  "versions": []
}