{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T11:05:03Z","timestamp":1789297503336,"version":"build-2803163510"},"posted":{"date-parts":[[2026,9,10]]},"group-title":"Genetics","reference-count":48,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["HL152163"],"award-info":[{"award-number":["HL152163"]}],"id":[{"id":"https:\/\/ror.org\/023ny1p48","id-type":"ROR","asserted-by":"publisher"}]},{"name":"The Gatorade Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The\n                  <jats:italic>STING<\/jats:italic>\n                  allele R71H-G230A-R293Q (\n                  <jats:italic>HAQ<\/jats:italic>\n                  ) was positively selected in Anatomically Modern Humans (AMH) during the Out of Africa (OoA) migration. Here, we show that 51.61% of Native Americans (NAM) are\n                  <jats:italic>HAQ\/HAQ<\/jats:italic>\n                  , while only 6.45% are\n                  <jats:italic>WT\/WT. HAQ<\/jats:italic>\n                  individuals are defective in DNA-induced type I IFNs responses, such as smallpox-induced IFN\u03b1 production. 82.3% of NAM carry the\n                  <jats:italic>HAQ<\/jats:italic>\n                  allele, which helps explain the post-Columbus NAM population collapse from the smallpox epidemic. Similarly, in 12 sub-groups of Sub-Saharan Africans, we found 0%\n                  <jats:italic>HAQ\/HAQ<\/jats:italic>\n                  , indicating ongoing negative selection reflecting Sub-Saharan Africa as the world\u2019s heaviest infectious-disease regions. To understand the positive selection of\n                  <jats:italic>HAQ<\/jats:italic>\n                  in non-Africans, we dephased\n                  <jats:italic>HAQ<\/jats:italic>\n                  haplotypes in 74 sub-populations worldwide, over ~4,000 individuals. We found that the\n                  <jats:italic>HAQ<\/jats:italic>\n                  allele evolved faster than the neutral\n                  <jats:italic>H232 STING<\/jats:italic>\n                  allele and had more generations during the OoA migration, increasing its frequency in non-Africans. A mouse model of\n                  <jats:italic>HAQ<\/jats:italic>\n                  housed in a Specific Pathogen-Free mouse facility generates more surviving pups than the\n                  <jats:italic>H232<\/jats:italic>\n                  mice. In summary, the\n                  <jats:italic>HAQ<\/jats:italic>\n                  allele was positively selected during OoA migration but is negatively selected in Sub-Saharan Africa, underscoring its essential role in AMH adaptation to diverse environments.\n                <\/jats:p>","DOI":"10.64898\/2026.09.04.749500","type":"posted-content","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T13:05:17Z","timestamp":1789045517000},"source":"Crossref","is-referenced-by-count":0,"title":["Natural Selection of the Common\n                  <i>STING<\/i>\n                  Allele\n                  <i>HAQ<\/i>\n                  in Anatomically Modern Humans"],"prefix":"10.64898","author":[{"given":"Alexandra","family":"Aybar-Torres","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Florida, Gainesville, FL 32610, U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6836-1142","authenticated-orcid":false,"given":"Lei","family":"Jin","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Florida, Gainesville, FL 32610, U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026091303100516000_2026.09.04.749500v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nature18964"},{"key":"2026091303100516000_2026.09.04.749500v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nature19792"},{"key":"2026091303100516000_2026.09.04.749500v1.3","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20921"},{"key":"2026091303100516000_2026.09.04.749500v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3559"},{"key":"2026091303100516000_2026.09.04.749500v1.5","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.gde.2020.06.003","article-title":"Human adaptation over the past 40,000 years","volume":"62","year":"2020","journal-title":"Curr Opin Genet Dev"},{"key":"2026091303100516000_2026.09.04.749500v1.6","doi-asserted-by":"publisher","DOI":"10.1126\/science.1198878"},{"key":"2026091303100516000_2026.09.04.749500v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/nri3921"},{"key":"2026091303100516000_2026.09.04.749500v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2010.12.015"},{"key":"2026091303100516000_2026.09.04.749500v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/gene.2010.75"},{"key":"2026091303100516000_2026.09.04.749500v1.10","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601585"},{"key":"2026091303100516000_2026.09.04.749500v1.11","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.4049\/jimmunol.2200158","article-title":"MPYS Modulates Fatty Acid Metabolism and Immune Tolerance at Homeostasis Independent of Type I IFNs","volume":"209","year":"2022","journal-title":"J Immunol"},{"key":"2026091303100516000_2026.09.04.749500v1.12","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00640-08"},{"key":"2026091303100516000_2026.09.04.749500v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/s41435-018-0029-9"},{"key":"2026091303100516000_2026.09.04.749500v1.14","doi-asserted-by":"crossref","unstructured":"A. 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