{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T20:55:47Z","timestamp":1790369747355,"version":"4.1.0"},"reference-count":121,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[1998,5,1]],"date-time":"1998-05-01T00:00:00Z","timestamp":893980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1998,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We have studied the genetic polymorphism at 10 Plasmodium falciparum loci that are considered potential targets for specific antimalarial vaccines. The polymorphism is unevenly distributed among the loci; loci encoding proteins expressed on the surface of the sporozoite or the merozoite (AMA-1, CSP, LSA-1, MSP-1, MSP-2, and MSP-3) are more polymorphic than those expressed during the sexual stages or inside the parasite (EBA-175, Pfs25, PF48\/45, and RAP-1). Comparison of synonymous and nonsynonymous substitutions indicates that natural selection may account for the polymorphism observed at seven of the 10 loci studied. This inference depends on the assumption that synonymous substitutions are neutral, which we test by analyzing codon bias and G+C content in a set of 92 gene loci. We find evidence for an overall trend towards increasing A+T richness, but no evidence for mutation bias. Although the neutrality of synonymous substitutions is not definitely established, this trend towards an A+T rich genome cannot explain the accumulation of substitutions at least in the case of four genes (AMA-1, CSP, LSA-1, and PF48\/45) because the G\u2194C transversions are more frequent than expected. Moreover, the Tajima test manifests positive natural selection for the MSP-1 and, less strongly, MSP-3 polymorphisms; the McDonald-Kreitman test manifests natural selection at LSA-1 and PF48\/45. We conclude that there is definite evidence for positive natural selection in the genes encoding AMA-1, CSP, LSA-1, MSP-1, and Pfs48\/45. For four other loci, EBA-175, MSP-2, MSP-3, and RAP-1, the evidence is limited. No evidence for natural selection is found for Pfs25.<\/jats:p>","DOI":"10.1093\/genetics\/149.1.189","type":"journal-article","created":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T22:43:44Z","timestamp":1613169824000},"page":"189-202","source":"Crossref","is-referenced-by-count":206,"title":["Genetic Polymorphism and Natural Selection in the Malaria Parasite Plasmodium falciparum"],"prefix":"10.1093","volume":"149","author":[{"given":"Ananias A","family":"Escalante","sequence":"first","affiliation":[{"name":"Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, US Public Health Service, Chamblee, Georgia 30341"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Altaf A","family":"Lal","sequence":"additional","affiliation":[{"name":"Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, US Public Health Service, Chamblee, Georgia 30341"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J","family":"Ayala","sequence":"additional","affiliation":[{"name":"Department of Ecology and Evolutionary Biology, University of California, Irvine, California 92697-2525"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[1998,5,1]]},"reference":[{"key":"2022010309011986700_R1","first-page":"169","article-title":"Candidate antigens for an asexual blood stage vaccine against falciparum malaria","volume-title":"Molecular Immunological Considerations in Malaria Vaccine Development","author":"Anders","year":"1994"},{"key":"2022010309011986700_R2","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1007\/BF02352282","article-title":"Codon usage and base composition in Rickettsia prowazekii","volume":"42","author":"Andersson","year":"1996","journal-title":"J. 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