Whole-Genome Scans Provide Evidence of Adaptive Evolution in Malawian Plasmodium falciparum Isolates

Autor: Kevin Marsh, Abdoulaye A. Djimde, Jacqui Montgomery, Issaka Zongo, Mark D. Preston, Alexis Nzila, Harold Ocholla, Susana Campino, Ogobara K. Doumbo, Alister Craig, Dominic P. Kwiatkowski, Anja T. R. Jensen, Daniel Alcock, Samuel Assefa, Jean Bosco Oudraogo, Steffen Borrmann, Mwapatsa Mipando, Rick M. Fairhurst, François Nosten, Tim J. Anderson, Taane G. Clark, Bronwyn MacInnis, Anja Terlouw
Rok vydání: 2014
Předmět:
Zdroj: The Journal of Infectious Diseases
Ocholla, H, Preston, M D, Mipando, M, Jensen, A T R, Campino, S, MacInnis, B, Alcock, D, Terlouw, A, Zongo, I, Oudraogo, J-B, Djimde, A A, Assefa, S, Doumbo, O K, Borrmann, S, Nzila, A, Marsh, K, Fairhurst, R M, Nosten, F, Anderson, T J C, Kwiatkowski, D P, Craig, A, Clark, T G & Montgomery, J 2014, ' Whole-Genome Scans Provide Evidence of Adaptive Evolution in Malawian Plasmodium falciparum Isolates ', The Journal of Infectious Diseases, vol. 210, no. 12, pp. 1991-2000 . https://doi.org/10.1093/infdis/jiu349
ISSN: 1537-6613
0022-1899
DOI: 10.1093/infdis/jiu349
Popis: BACKGROUND\ud Selection by host immunity and antimalarial drugs has driven extensive adaptive evolution in Plasmodium falciparum, and continues to produce ever-changing landscapes of genetic variation.\ud \ud METHODS\ud We carried out whole-genome sequencing of 69 P. falciparum isolates from Malawi and used population genetics approaches to investigate genetic diversity and population structure, and identify loci under selection.\ud \ud RESULTS\ud High genetic diversity (π=2.4 x 10(-4)), moderately high multiplicity of infection (2.7), and low linkage disequilibrium (500-bp) were observed in Chikhwawa District, Malawi, an area of high malaria transmission. Allele frequency-based tests provided evidence of recent population growth in Malawi and detected potential targets of host immunity and candidate vaccine antigens. Comparing the sequence variation between isolates from Malawi and those from 5 geographically dispersed countries (Kenya, Burkina Faso, Mali, Cambodia, and Thailand) detected population genetic differences between Africa and Asia, within Southeast Asia, and within Africa. Applying haplotype-based tests of selection to sequence data from all 6 populations identified signals of directional selection at known drug-resistance loci, including pfcrt, pfdhps, pfmdr1, and pfgch1.\ud \ud CONCLUSIONS\ud The sequence variations observed at drug-resistance loci reflect differences in each country's historical use of antimalarial drugs, and may be useful in formulating local malaria treatment guidelines.
Databáze: OpenAIRE