{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:51:44Z","timestamp":1791327104301,"version":"4.3.1"},"reference-count":72,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2015,3,10]],"date-time":"2015-03-10T00:00:00Z","timestamp":1425945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The question of the origin of smallpox, one of the major menaces to humankind, is a constant concern for the scientific community. Smallpox is caused by the agent referred to as the variola virus (VARV), which belongs to the genus Orthopoxvirus. In the last century, smallpox was declared eradicated from the human community; however, the mechanisms responsible for the emergence of new dangerous pathogens have yet to be unraveled. Evolutionary analyses of the molecular biological genomic data of various orthopoxviruses, involving a wide range of epidemiological and historical information about smallpox, have made it possible to date the emergence of VARV. Comparisons of the VARV genome to the genomes of the most closely related orthopoxviruses and the examination of the distribution their natural hosts\u2019 ranges suggest that VARV emerged 3000 to 4000 years ago in the east of the African continent. The VARV evolution rate has been estimated to be approximately 2 \u00d7 10\u22126 substitutions\/site\/year for the central conserved genomic region and 4 \u00d7 10\u22126 substitutions\/site\/year for the synonymous substitutions in the genome. Presumably, the introduction of camels to Africa and the concurrent changes to the climate were the particular factors that triggered the divergent evolution of a cowpox-like ancestral virus and thereby led to the emergence of VARV.<\/jats:p>","DOI":"10.3390\/v7031100","type":"journal-article","created":{"date-parts":[[2015,3,10]],"date-time":"2015-03-10T10:59:09Z","timestamp":1425985149000},"page":"1100-1112","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":91,"title":["The Origin of the Variola Virus"],"prefix":"10.3390","volume":"7","author":[{"given":"Igor","family":"Babkin","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Microbiology, Institute of Chemical Biology and Fundamental Medicine, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Babkina","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Microbiology, Institute of Chemical Biology and Fundamental Medicine, Novosibirsk 630090, Russia"},{"name":"JSC VECTOR-BEST, Novosibirsk 630559, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1056\/NEJMra020025","article-title":"Diagnosis and management of smallpox","volume":"346","author":"Breman","year":"2002","journal-title":"N. 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