{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T19:33:17Z","timestamp":1786649597997,"version":"build-2736575974"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      This study aims to identify the signatures of natural selection in the pyrazinamidase (\n                      <jats:italic toggle=\"yes\">pncA<\/jats:italic>\n                      ) gene to see if genetic adaptations by Darwinian natural selection have shaped genetic composition of\n                      <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                      (Mtb).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      The present analyses were based on 209 DNA sequences (561 bp) of the\n                      <jats:italic toggle=\"yes\">pncA<\/jats:italic>\n                      gene of the bacterial pathogen, Mtb from seven different counties (Peru, Pakistan, South Africa, Mexico, India, China, and Kuwait) endemic to tuberculosis (TB). Before conducting tests for Darwinian natural selection in the\n                      <jats:italic toggle=\"yes\">pncA<\/jats:italic>\n                      gene, we conducted several tests for neutrality in all the available DNA sequences after retrieval from public domains. Several statistical analyses under different algorithms were conducted and biological\/evolutionary inferences were drawn.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      The 209 sequences of the\n                      <jats:italic toggle=\"yes\">pncA<\/jats:italic>\n                      gene in\n                      <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                      belonging to seven different countries were found to be perfectly aligned with the reference sequence. Data analyses under different population genetic models revealed the highest genetic diversity in India, followed by Peru; the lowest was in China. Interestingly, four populations; Peru, Pakistan, India, and Kuwait were found to be deviated from neutral model of evolution based on Tajima\u2019D (TD) values; two populations (India and Peru) based on Fu and Li\u2019s D and F (FLD and FLF) test values and five populations (India, Peru, Pakistan, South Africa, and Kuwait) based on Fay and Wu\u2019s H (FWH) test. Moreover, based on the statistically significant results of neutrality tests, evidence for positive selection in three populations (Peru [\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.02945], Pakistan [\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.01767], and Kuwait [\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.00301]) at\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.05 level of significance] was found.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      The present evolutionary genetic analysis of the\n                      <jats:italic toggle=\"yes\">pncA<\/jats:italic>\n                      gene indicates different levels of genetic diversity in seven different country populations. As almost all the global populations showed deviation from neutral model and three populations showed signatures of natural selection, with no specific hotspot region identified for PZA resistance, this gene needs to be studied with larger population size covering countries with TB incidences to study the evolution of drug resistance in\n                      <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                      . This will help in the management of drug resistance and TB elimination plan.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/ijmy.ijmy_30_25","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T15:00:07Z","timestamp":1750431607000},"page":"132-139","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Evolutionary Genetic Analysis of the Pyrazinamidase Gene in Seven Global Populations of Mycobacterium tuberculosis"],"prefix":"10.4103","volume":"14","author":[{"given":"Neha","family":"Kumari","sequence":"first","affiliation":[{"name":"Department of Genomic Epidemiology, ICMR-National Institute of Research in Tribal Health, Jabalpur, Madhya Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikhat","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Genomic Epidemiology, ICMR-National Institute of Research in Tribal Health, Jabalpur, Madhya Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4081-5816","authenticated-orcid":false,"given":"Aparup","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Genomic Epidemiology, ICMR-National Institute of Research in Tribal Health, Jabalpur, Madhya Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"R4-20260422","doi-asserted-by":"crossref","first-page":"320","DOI":"10.4103\/ijmy.ijmy_144_19","article-title":"Diversified lineages and drug-resistance profiles of clinical isolates of Mycobacterium tuberculosis complex in Malaysia","volume":"8","author":"nNoorizhab Fakhruzzaman","year":"2019","journal-title":"Int J Mycobacteriol"},{"key":"R5-20260422","doi-asserted-by":"crossref","first-page":"213","DOI":"10.4103\/ijmy.ijmy_85_17","article-title":"Fighting tuberculosis by drugs targeting nonreplicating Mycobacterium tuberculosis bacilli","volume":"6","author":"Iacobino","year":"2017","journal-title":"Int J Mycobacteriol"},{"key":"R6-20260422","doi-asserted-by":"crossref","first-page":"954074","DOI":"10.3389\/fcimb.2022.954074","article-title":"Evolution of Mycobacterium tuberculosis drug resistance in the genomic era","volume":"12","author":"Nimmo","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"key":"R7-20260422","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1093\/jac\/dkx506","article-title":"Evolution of drug resistance in Mycobacterium tuberculosis: A review on the molecular determinants of resistance and implications for personalized care","volume":"73","author":"Dookie","year":"2018","journal-title":"J Antimicrob Chemother"},{"key":"R8-20260422","doi-asserted-by":"crossref","first-page":"258","DOI":"10.4103\/ijmy.ijmy_202_23","article-title":"Diagnostic accuracy of FluoroCycler XT MTBDR assay for detection of rifampicin and isoniazid-resistant Mycobacteria tuberculosis in clinical isolates from Kenya","volume":"13","author":"Mwangi","year":"2024","journal-title":"Int J Mycobacteriol"},{"key":"R9-20260422","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1128\/AAC.00110-08","article-title":"Pyrazinamide resistance and pncA gene mutations in Mycobacterium tuberculosis","volume":"52","author":"Jur\u00e9en","year":"2008","journal-title":"Antimicrob Agents Chemother"},{"key":"R10-20260422","doi-asserted-by":"crossref","first-page":"4985","DOI":"10.2147\/IDR.S368444","article-title":"Pyrazinamide resistance and pncA mutation profiles in multidrug resistant Mycobacterium tuberculosis","volume":"15","author":"Shi","year":"2022","journal-title":"Infect Drug Resist"},{"key":"R11-20260422","doi-asserted-by":"crossref","first-page":"191","DOI":"10.4103\/ijmy.ijmy_69_24","article-title":"Evaluation of colorimetric nitrate reductase assay in liquid medium for detection of resistance to first-line antitubercular drugs","volume":"13","author":"Aman","year":"2024","journal-title":"Int J Mycobacteriol"},{"key":"R12-20260422","doi-asserted-by":"crossref","first-page":"5267","DOI":"10.1128\/AAC.00204-15","article-title":"Systematic review of mutations in pyrazinamidase associated with pyrazinamide resistance in Mycobacterium tuberculosis clinical isolates","volume":"59","author":"Ramirez-Busby","year":"2015","journal-title":"Antimicrob Agents Chemother"},{"key":"R13-20260422","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.ijpara.2011.03.002","article-title":"Population genetic analyses of Plasmodium falciparum chloroquine receptor transporter gene haplotypes reveal the evolutionary history of chloroquine-resistant malaria in India","volume":"41","author":"Awasthi","year":"2011","journal-title":"Int J Parasitol"},{"key":"R14-20260422","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.pt.2023.03.006","article-title":"How can the complex epidemiology of malaria in India impact its elimination?","volume":"39","author":"Khan","year":"2023","journal-title":"Trends Parasitol"},{"key":"R15-20260422","doi-asserted-by":"crossref","first-page":"3022","DOI":"10.1093\/molbev\/msab120","article-title":"MEGA11: Molecular evolutionary genetics analysis version 11","volume":"38","author":"Tamura","year":"2021","journal-title":"Mol Biol Evol"},{"key":"R16-20260422","doi-asserted-by":"crossref","first-page":"7068","DOI":"10.1038\/s41467-022-34853-x","article-title":"A comprehensive update to the Mycobacterium tuberculosis H37Rv reference genome","volume":"13","author":"Chitale","year":"2022","journal-title":"Nat Commun"},{"key":"R17-20260422","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1471-2156-9-8","article-title":"Insertion-deletion polymorphisms (indels) as genetic markers in natural populations","volume":"9","author":"V\u00e4li","year":"2008","journal-title":"BMC Genet"},{"key":"R18-20260422","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/0040-5809(75)90020-9","article-title":"On the number of segregating sites in genetical models without recombination","volume":"7","author":"Watterson","year":"1975","journal-title":"Theor Popul Biol"},{"key":"R20-20260422","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1093\/genetics\/133.3.693","article-title":"Statistical tests of neutrality of mutations","volume":"133","author":"Fu","year":"1993","journal-title":"Genetics"},{"key":"R21-20260422","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1093\/genetics\/123.3.585","article-title":"Statistical method for testing the neutral mutation hypothesis by DNA polymorphism","volume":"123","author":"Tajima","year":"1989","journal-title":"Genetics"},{"key":"R22-20260422","doi-asserted-by":"crossref","first-page":"e311","DOI":"10.1371\/journal.pbio.0060311","article-title":"High functional diversity in Mycobacterium tuberculosis driven by genetic drift and human demography","volume":"6","author":"Hershberg","year":"2008","journal-title":"PLoS Biol"},{"key":"R23-20260422","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s10709-014-9775-4","article-title":"Molecular population genetics of the NADPH cytochrome P450 reductase (CPR) gene in Anopheles minimus","volume":"142","author":"Srivastava","year":"2014","journal-title":"Genetica"},{"key":"R24-20260422","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1093\/genetics\/116.1.153","article-title":"A test of neutral molecular evolution based on nucleotide data","volume":"116","author":"Hudson","year":"1987","journal-title":"Genetics"},{"key":"R25-20260422","doi-asserted-by":"crossref","first-page":"e1000304","DOI":"10.1371\/journal.pgen.1000304","article-title":"The population genetics of dN\/dS","volume":"4","author":"Kryazhimskiy","year":"2008","journal-title":"PLoS Genet"},{"key":"R26-20260422","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1101\/gr.200901","article-title":"The K(A)\/K(S) ratio test for assessing the protein-coding potential of genomic regions: An empirical and simulation study","volume":"12","author":"Nekrutenko","year":"2002","journal-title":"Genome Res"},{"key":"R27-20260422","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1038\/351652a0","article-title":"Adaptive protein evolution at the ADH locus in Drosophila","volume":"351","author":"McDonald","year":"1991","journal-title":"Nature"},{"key":"R28-20260422","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-319-64371-7_1","article-title":"The nature and evolution of genomic diversity in the Mycobacterium tuberculosis complex","volume":"1019","author":"Brites","year":"2017","journal-title":"Adv Exp Med Biol"},{"key":"R29-20260422","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1089\/mdr.2017.0234","article-title":"Prevalence of pyrazinamide resistance in Khyber Pakhtunkhwa, Pakistan","volume":"24","author":"Khan","year":"2018","journal-title":"Microb Drug Resist"},{"key":"R30-20260422","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.3201\/eid1209.050017","article-title":"Predominance of ancestral lineages of Mycobacterium tuberculosis in India","volume":"12","author":"Gutierrez","year":"2006","journal-title":"Emerg Infect Dis"},{"key":"R31-20260422","first-page":"892","article-title":"A study of Mycobacterium tuberculosis genotypic diversity and drug resistance mutations in Varanasi, North India","volume":"139","author":"Gupta","year":"2014","journal-title":"Indian J Med Res"},{"key":"R32-20260422","doi-asserted-by":"crossref","first-page":"894","DOI":"10.5588\/ijtld.16.0850","article-title":"Prevalence of pyrazinamide resistance and Wayne assay performance analysis in a tuberculosis cohort in Lima, Peru","volume":"21","author":"Calder\u00f3n","year":"2017","journal-title":"Int J Tuberc Lung Dis"},{"key":"R33-20260422","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s40001-019-0397-2","article-title":"Molecular characterization of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates identifies local transmission of infection in Kuwait, a country with a low incidence of TB and MDR-TB","volume":"24","author":"Al-Mutairi","year":"2019","journal-title":"Eur J Med Res"},{"key":"R34-20260422","doi-asserted-by":"crossref","first-page":"633365","DOI":"10.3389\/fmolb.2021.633365","article-title":"Insights into mutations induced conformational changes and rearrangement of Fe(2+) Ion in pncA gene of Mycobacterium tuberculosis to decipher the mechanism of resistance to pyrazinamide","volume":"8","author":"Nangraj","year":"2021","journal-title":"Front Mol Biosci"},{"key":"R35-20260422","doi-asserted-by":"crossref","first-page":"35565","DOI":"10.1039\/D0RA06072K","article-title":"Pyrazinamide resistance of novel mutations in pncA and their dynamic behavior","volume":"10","author":"Ali","year":"2020","journal-title":"RSC Adv"}],"container-title":["The International Journal of Mycobacteriology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/ijmy.ijmy_30_25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T18:55:47Z","timestamp":1786647347000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/ijmy.ijmy_30_25"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":31,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.4103\/ijmy.ijmy_30_25","relation":{},"ISSN":["2212-5531","2212-554X"],"issn-type":[{"value":"2212-5531","type":"print"},{"value":"2212-554X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4]]},"assertion":[{"value":"2025-02-21","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-09","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}