TY - JOUR

T1 - Whole-Genome Scans Provide Evidence of Adaptive Evolution in Malawian Plasmodium falciparum Isolates

AU - Ocholla, Harold

AU - Preston, Mark D

AU - Mipando, Mwapatsa

AU - Jensen, Anja Tatiana Ramstedt

AU - Campino, Susana

AU - MacInnis, Bronwyn

AU - Alcock, Daniel

AU - Terlouw, Anja

AU - Zongo, Issaka

AU - Oudraogo, Jean-Bosco

AU - Djimde, Abdoulaye A

AU - Assefa, Samuel

AU - Doumbo, Ogobara K

AU - Borrmann, Steffen

AU - Nzila, Alexis

AU - Marsh, Kevin

AU - Fairhurst, Rick M

AU - Nosten, Francois

AU - Anderson, Tim J C

AU - Kwiatkowski, Dominic P

AU - Craig, Alister

AU - Clark, Taane G

AU - Montgomery, Jacqui

N1 - © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

PY - 2014/6/19

Y1 - 2014/6/19

N2 - 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 performed 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 × 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. Comparison of 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. 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.

AB - 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 performed 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 × 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. Comparison of 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. 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.

U2 - 10.1093/infdis/jiu349

DO - 10.1093/infdis/jiu349

M3 - Journal article

C2 - 24948693

VL - 210

SP - 1991

EP - 2000

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 12

ER -