Whole-genome scans provide evidence of adaptive evolution in Malawian Plasmodium falciparum isolates

Ocholla, Harold, Preston, Mark D, Mipando, Mwapatsa, Jensen, Anja Tr, Campino, Susana, MacInnis, Bronwyn, Alcock, Daniel, Terlouw, Anja ORCID: https://orcid.org/0000-0001-5327-8995, Zongo, Issaka, Oudraogo, Jean-Bosco, Djimde, Abdoulaye A, Assefa, Samuel, Doumbo, Ogobara K, Borrmann, Steffen, Nzila, Alexis, Marsh, Kevin, Fairhurst, Rick M, Nosten, Francois, Anderson, Tim Jc, Kwiatkowski, Dominic P, Craig, Alister ORCID: https://orcid.org/0000-0003-0914-6164, Clark, Taane G and Montgomery, Jacqui (2014) 'Whole-genome scans provide evidence of adaptive evolution in Malawian Plasmodium falciparum isolates'. Journal of Infectious Disease, Vol 210, Issue 12, pp. 1991-2000.

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Abstract

BACKGROUND
 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.

METHODS
 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.

RESULTS
 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.

CONCLUSIONS
 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.

Item Type:	Article
Subjects:	QU Biochemistry > Genetics > QU 470 Genetic structures QU Biochemistry > Genetics > QU 550 Genetic techniques. PCR. Chromosome mapping QX Parasitology > Protozoa > QX 135 Plasmodia WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries WS Pediatrics > Diseases of Children and Adolescents > By System > WS 300 Hemic and lymphatic system
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1093/infdis/jiu349
Depositing User:	Mary Creegan
Date Deposited:	27 Aug 2014 11:48
Last Modified:	17 Jul 2020 10:59
URI:	https://archive.lstmed.ac.uk/id/eprint/3834

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