{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:42:52Z","timestamp":1791380572207,"version":"4.3.3"},"reference-count":109,"publisher":"National Academy of Sciences","issue":"35","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000925","name":"John Templeton Foundation","doi-asserted-by":"publisher","award":["61129"],"award-info":[{"award-number":["61129"]}],"id":[{"id":"10.13039\/100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000925","name":"John Templeton Foundation","doi-asserted-by":"publisher","award":["62220"],"award-info":[{"award-number":["62220"]}],"id":[{"id":"10.13039\/100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["3757\/20"],"award-info":[{"award-number":["3757\/20"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,9,2]]},"abstract":"<jats:p>\n                    Mutation rates have long been measured as averages across many genomic positions. Recently, a method to measure the rates of individual mutations was applied to a narrow region in the human hemoglobin subunit beta (\n                    <jats:italic toggle=\"yes\">HBB<\/jats:italic>\n                    ) gene containing the site of the hemoglobin S (HbS) mutation as well as to a paralogous hemoglobin subunit delta (\n                    <jats:italic toggle=\"yes\">HBD<\/jats:italic>\n                    ) region, in sperm samples from sub-Saharan African and northern European donors [Melamed\n                    <jats:italic toggle=\"yes\">et al<\/jats:italic>\n                    .,\n                    <jats:italic toggle=\"yes\">Genome Res.<\/jats:italic>\n                    <jats:bold>32<\/jats:bold>\n                    , 488\u2013498 (2022)]. The HbS mutation, which protects against malaria while causing sickle-cell anemia in homozygotes, originated de novo significantly more frequently in the\n                    <jats:italic toggle=\"yes\">HBB<\/jats:italic>\n                    gene in Africans compared to the other three test cases combined (the European\n                    <jats:italic toggle=\"yes\">HBB<\/jats:italic>\n                    gene and the European and African\n                    <jats:italic toggle=\"yes\">HBD<\/jats:italic>\n                    gene). Here, we apply this approach to the human apolipoprotein L1 (\n                    <jats:italic toggle=\"yes\">APOL1<\/jats:italic>\n                    ) gene containing the site of the G1 1024A\u2192G mutation, which protects against African sleeping sickness caused by\n                    <jats:italic toggle=\"yes\">Trypanosoma brucei gambiense<\/jats:italic>\n                    while causing a substantially increased risk of chronic kidney disease in homozygotes. We find that the 1024A\u2192G mutation is the mutation of highest de novo origination rate and deviates most from the genome-wide average rate for its type (A\u2192G) compared to all other observable mutations in the region and that it originates de novo significantly more frequently in Africans than in Europeans\u2014i.e., in the population where it is of adaptive significance. The results are unexpected given the notion that the probability of a specific mutational event is independent of its value to the organism and underscore the importance of studying mutation rates at the individual-mutation resolution.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2424538122","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T19:06:57Z","timestamp":1756148817000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":4,"title":["De novo rates of a\n                    <i>Trypanosoma<\/i>\n                    -resistant mutation in two human populations"],"prefix":"10.1073","volume":"122","author":[{"given":"Daniel","family":"Melamed","sequence":"first","affiliation":[{"name":"Department of Evolutionary and Environmental Biology","place":["Haifa, Israel"]},{"name":"University of Haifa","place":["Haifa, Israel"]},{"name":"Institute of Evolution, Faculty of Natural Sciences","place":["Haifa, Israel"]},{"name":"University of Haifa","place":["Haifa, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2242-7968","authenticated-orcid":false,"given":"Revital","family":"Shemer","sequence":"additional","affiliation":[{"name":"The Ruth and Bruce Rappaport Faculty of Medicine & Research Institute","place":["Haifa, Israel"]},{"name":"Technion\u2013Israel Institute of Technology","place":["Haifa, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6581-3262","authenticated-orcid":false,"given":"Evgeni","family":"Bolotin","sequence":"additional","affiliation":[{"name":"Department of Evolutionary and Environmental Biology","place":["Haifa, Israel"]},{"name":"University of Haifa","place":["Haifa, Israel"]},{"name":"Institute of Evolution, Faculty of Natural Sciences","place":["Haifa, Israel"]},{"name":"University of Haifa","place":["Haifa, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6903-0633","authenticated-orcid":false,"given":"Michael B.","family":"Yakass","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cell and Molecular Biology","place":["Legon, Ghana"]},{"name":"West African Centre for Cell Biology of Infectious Pathogens","place":["Legon, Ghana"]},{"name":"University of Ghana","place":["Legon, Ghana"]},{"name":"Assisted Conception Unit","place":["Accra, Ghana"]},{"name":"Lister Hospital & Fertility Centre","place":["Accra, Ghana"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorit","family":"Fink-Barkai","sequence":"additional","affiliation":[{"name":"Department of Evolutionary and Environmental Biology","place":["Haifa, Israel"]},{"name":"University of Haifa","place":["Haifa, Israel"]},{"name":"Institute of Evolution, Faculty of Natural Sciences","place":["Haifa, Israel"]},{"name":"University of Haifa","place":["Haifa, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edem K.","family":"Hiadzi","sequence":"additional","affiliation":[{"name":"Assisted Conception Unit","place":["Accra, Ghana"]},{"name":"Lister Hospital & Fertility Centre","place":["Accra, Ghana"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0900-3406","authenticated-orcid":false,"given":"Karl L.","family":"Skorecki","sequence":"additional","affiliation":[{"name":"The Azrieli Faculty of Medicine","place":["Safed, Israel"]},{"name":"Bar-Ilan University","place":["Safed, Israel"]},{"name":"Rambam Health Care Campus","place":["Haifa, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7304-8871","authenticated-orcid":false,"given":"Adi","family":"Livnat","sequence":"additional","affiliation":[{"name":"Department of Evolutionary and Environmental Biology","place":["Haifa, Israel"]},{"name":"University of Haifa","place":["Haifa, Israel"]},{"name":"Institute of Evolution, Faculty of Natural Sciences","place":["Haifa, Israel"]},{"name":"University of Haifa","place":["Haifa, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2025,8,25]]},"reference":[{"key":"e_1_3_4_1_2","volume-title":"The Variation of Animals and Plants under Domestication","author":"Darwin C.","year":"1868","unstructured":"C. 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