دورية أكاديمية
Genomic variation during culture adaptation of genetically complex Plasmodium falciparum clinical isolates.
| العنوان: | Genomic variation during culture adaptation of genetically complex Plasmodium falciparum clinical isolates. |
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| المؤلفون: | Claessens A; LPHI, MIVEGEC, INSERM, CNRS, IRD, University of Montpellier, France.; Department of Infection Biology, London School of Hygiene and Tropical Medicine, Keppel St, London, WC1E 7HT, UK.; MRC Unit The Gambia at London School of Hygiene and Tropical Medicine, Banjul, The Gambia., Stewart LB; Department of Infection Biology, London School of Hygiene and Tropical Medicine, Keppel St, London, WC1E 7HT, UK., Drury E; Wellcome Sanger Institute, Cambridge, CB10 1SA, UK., Ahouidi AD; Le Dantec Hospital, Université Cheikh Anta Diop, Dakar, Senegal., Amambua-Ngwa A; MRC Unit The Gambia at London School of Hygiene and Tropical Medicine, Banjul, The Gambia., Diakite M; Malaria Research and Training Center, University of Bamako, Bamako, Mali., Kwiatkowski DP; Wellcome Sanger Institute, Cambridge, CB10 1SA, UK., Awandare GA; West African Centre for Cell Biology of Infectious Pathogens, Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Legon, Ghana., Conway DJ; Department of Infection Biology, London School of Hygiene and Tropical Medicine, Keppel St, London, WC1E 7HT, UK. |
| المصدر: | Microbial genomics [Microb Genom] 2023 May; Vol. 9 (5). |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Microbiology Society Country of Publication: England NLM ID: 101671820 Publication Model: Print Cited Medium: Internet ISSN: 2057-5858 (Electronic) Linking ISSN: 20575858 NLM ISO Abbreviation: Microb Genom Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Oct. 2015- : [London] : Microbiology Society Original Publication: [London] : Society for General Microbiology, [2015]- |
| مواضيع طبية MeSH: | Plasmodium falciparum*/genetics , Malaria*, Humans ; Genotype ; Genomics ; Guanine Nucleotide Exchange Factors/genetics ; Protein Serine-Threonine Kinases/genetics |
| مستخلص: | Experimental studies on the biology of malaria parasites have mostly been based on laboratory-adapted lines, but there is limited understanding of how these may differ from parasites in natural infections. Loss-of-function mutants have previously been shown to emerge during culture of some Plasmodium falciparum clinical isolates in analyses focusing on single-genotype infections. The present study included a broader array of isolates, mostly representing multiple-genotype infections, which are more typical in areas where malaria is highly endemic. Genome sequence data from multiple time points over several months of culture adaptation of 28 West African isolates were analysed, including previously available sequences along with new genome sequences from additional isolates and time points. Some genetically complex isolates eventually became fixed over time to single surviving genotypes in culture, whereas others retained diversity, although proportions of genotypes varied over time. Drug resistance allele frequencies did not show overall directional changes, suggesting that resistance-associated costs are not the main causes of fitness differences among parasites in culture. Loss-of-function mutants emerged during culture in several of the multiple-genotype isolates, affecting genes (including AP2-HS , EPAC and SRPK1 ) for which loss-of-function mutants were previously seen to emerge in single-genotype isolates. Parasite clones were derived by limiting dilution from six of the isolates, and sequencing identified de novo variants not detected in the bulk isolate sequences. Interestingly, several of these were nonsense mutants and frameshifts disrupting the coding sequence of EPAC , the gene with the largest number of independent nonsense mutants previously identified in laboratory-adapted lines. Analysis of genomic identity by descent to explore relatedness among clones revealed co-occurring non-identical sibling parasites, illustrative of the natural genetic structure within endemic populations. |
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| معلومات مُعتمدة: | 206194 United Kingdom WT_ Wellcome Trust; 090770 United Kingdom WT_ Wellcome Trust; G1100123 United Kingdom MRC_ Medical Research Council; 098051 United Kingdom WT_ Wellcome Trust; United Kingdom WT_ Wellcome Trust; MR/S009760/1 United Kingdom MRC_ Medical Research Council |
| فهرسة مساهمة: | Keywords: adaptation; culture; genomic relatedness; loss-of-function mutants; mixed genotypes |
| المشرفين على المادة: | 0 (Guanine Nucleotide Exchange Factors) EC 2.7.1.- (SRPK1 protein, human) EC 2.7.11.1 (Protein Serine-Threonine Kinases) |
| تواريخ الأحداث: | Date Created: 20230519 Date Completed: 20230522 Latest Revision: 20240320 |
| رمز التحديث: | 20240320 |
| مُعرف محوري في PubMed: | PMC10272863 |
| DOI: | 10.1099/mgen.0.001009 |
| PMID: | 37204422 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2057-5858 |
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| DOI: | 10.1099/mgen.0.001009 |