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

Harold Ocholla, Mark D Preston, Mwapatsa Mipando, Anja T R Jensen, Susana Campino, Bronwyn MacInnis, Daniel Alcock, Anja Terlouw, Issaka Zongo, Jean-Bosco Oudraogo, Abdoulaye A Djimde, Samuel Assefa, Ogobara K Doumbo, Steffen Borrmann, Alexis Nzila, Kevin Marsh, Rick M Fairhurst, Francois Nosten, Tim J C Anderson, Dominic P Kwiatkowski, Alister Craig, Taane G Clark, Jacqui Montgomery, Harold Ocholla, Mark D Preston, Mwapatsa Mipando, Anja T R Jensen, Susana Campino, Bronwyn MacInnis, Daniel Alcock, Anja Terlouw, Issaka Zongo, Jean-Bosco Oudraogo, Abdoulaye A Djimde, Samuel Assefa, Ogobara K Doumbo, Steffen Borrmann, Alexis Nzila, Kevin Marsh, Rick M Fairhurst, Francois Nosten, Tim J C Anderson, Dominic P Kwiatkowski, Alister Craig, Taane G Clark, Jacqui Montgomery

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 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.

Keywords: Malawi; Plasmodium falciparum; genetic epidemiology; genomes.

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

Figures

Figure 1.
Figure 1.
Decay in linkage disequilibrium (LD) between populations. LD decays rapidly in Malawi, compared with Southeast Asian populations.
Figure 2.
Figure 2.
Positive directional selection in the Malawian Plasmodium falciparum population. Dashed line indicates genome-wide integrated haplotype scores at a significance threshold of P < .0006. Vertical lines indicate (from left) locations of pfdhfr, pfmdr1, pfcrt, and pfdhps, respectively.
Figure 3.
Figure 3.
Principal components analysis using single-nucleotide polymorphisms differentiates Plasmodium falciparum isolates by continent and within Southeast Asia (A) and between East and West Africa (B). The proportion of variation explained by the first 2 principal components is 13.4% (A) and 3.8% (B).

References

    1. World Health Organization. Geneva: WHO; 2012. World malaria report, 2012.
    1. Ewing VL, Lalloo DG, Phiri KS, Roca-Feltrer A, Mangham LJ, SanJoaquin MA. Seasonal and geographic differences in treatment-seeking and household cost of febrile illness among children in Malawi. Malar J. 2011;10:32.
    1. Roca-Feltrer A, Kwizombe CJ, Sanjoaquin MA, et al. Lack of decline in childhood malaria, Malawi, 2001–2010. Emerg Infect Dis. 2012;18:272–8.
    1. Mathanga D, Walker E, Wilson M, Ali D. Malaria control in Malawi: current status and directions for the future. Acta Trop. 2012;121:212–7.
    1. Volkman SK, Sabeti PC, DeCaprio D, et al. A genome-wide map of diversity in Plasmodium falciparum. Nat Genet. 2007;39:113–9.
    1. Kidgell C, Volkman SK, Daily J, et al. A systematic map of genetic variation in Plasmodium falciparum. PLoS Pathog. 2006;2:e57.
    1. Mackinnon MJ, Marsh K. The selection landscape of malaria parasites. Science. 2010;328:866–71.
    1. Tajima F. Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics. 1989;123:585–95.
    1. Mzilahowa T, Hastings IM, Molyneux ME, McCall PJ. Entomological indices of malaria transmission in Chikhwawa district, Southern Malawi. Malar J; 2012;11:380.
    1. Gething PW, Patil AP, Smith DL, et al. A new world malaria map: Plasmodium falciparum endemicity in 2010. Malar J. 2011;10:378.
    1. WHO Library Cataloguing-in-Publication Data. Focus on Malawi. Roll Back Malaria Partnership. Progress and Impact Series, n. 6. Country Reports. 2013.
    1. Venkatesan M, Amaratunga C, Campino S, et al. Using CF11 cellulose columns to inexpensively and effectively remove human DNA from Plasmodium falciparum-infected whole blood samples. Malar J. 2012;11:41.
    1. Auburn S, Campino S, Clark TG, et al. An effective method to purify Plasmodium falciparum DNA directly from clinical blood samples for whole genome high-throughput sequencing. PLoS One. 2011;6:e22213.
    1. Bentley DR, Balasubramanian S, Swerdlow HP, et al. Accurate whole human genome sequencing using reversible terminator chemistry. Nature. 2008;456:53–9.
    1. Robinson T, Campino SG, Auburn S, et al. Drug-resistant genotypes and multi-clonality in Plasmodium falciparum analysed by direct genome sequencing from peripheral blood of malaria patients. PLoS One. 2011;6:e23204.
    1. Preston MD, Assefa SA, Ocholla H, et al. PlasmoView: A web-based resource to visualise global Plasmodium falciparum genomic variation. J Infect Dis. 2014;209:1808–15.
    1. Li H, Handsaker B, Wysoker A, et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics. 2009;25:2078–9.
    1. Manske M, Miotto O, Campino S, et al. Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing. Nature. 2012;487:375–9.
    1. Sander AF, Lavstsen T, Rask TS, et al. DNA secondary structures are associated with recombination in major Plasmodium falciparum variable surface antigen gene families. Nucleic Acids Res. 2013;42:2270–81.
    1. Librado P, Rozas J. DnaSP v5: a software for comprehensive analysis of DNA polymorphism data. Bioinformatics. 2009;25:1451–2.
    1. Fu Y. Statistical tests of neutrality of mutations against population growth, hitchhiking and background selection. Genetics. 1997;147:915–25.
    1. Voight BF, Kudaravalli S, Wen X, Pritchard JK. A map of recent positive selection in the human genome. PLoS Biol. 2006;4:e72.
    1. Chang H-H, Park DJ, Galinsky KJ, et al. Genomic sequencing of Plasmodium falciparum malaria parasites from Senegal reveals the demographic history of the population. Mol Biol Evol. 2012;29:3427–39.
    1. Assefa SA, Preston MD, Campino S, Ocholla H, Sutherland CJ, Clark TG. estMOI: estimating multiplicity of infection using parasite deep sequencing data. Bioinformatics. 2014;30:1292–4.
    1. Jiang H, Li N, Gopalan V, et al. High recombination rates and hotspots in a Plasmodium falciparum genetic cross. Genome Biol. 2011;12:R33.
    1. Sabeti PC, Varilly P, Fry B, et al. Genome-wide detection and characterization of positive selection in human populations. Nature. 2007;449:913–8.
    1. Holsinger KE, Weir BS. Genetics in geographically structured populations: defining, estimating and interpreting F(ST) Nat Rev Genet. 2009;10:639–50.
    1. Hill WG, Robertson A. Linkage disequilibrium in finite populations. Theor Appl Genet. 1968;38:226–31.
    1. Volkman SK, Neafsey DE, Schaffner SF, Park DJ, Wirth DF. Harnessing genomics and genome biology to understand malaria biology. Nat Rev Genet; 2012;13:315–28.
    1. Bailey JA, Mvalo T, Aragam N, et al. Use of massively parallel pyrosequencing to evaluate the diversity of and selection on Plasmodium falciparum csp T-cell epitopes in Lilongwe, Malawi. J Infect Dis. 2012;206:580–7.
    1. Borrmann S, Straimer J, Mwai L, et al. Genome-wide screen identifies new candidate genes associated with artemisinin susceptibility in Plasmodium falciparum in Kenya. Sci Rep. 2013;3:3318.
    1. Mu J, Awadalla P, Duan J, et al. Genome-wide variation and identification of vaccine targets in the Plasmodium falciparum genome. Nat Genet. 2007;39:126–30.
    1. Amambua-Ngwa A, Park DJ, Volkman SK, et al. SNP genotyping identifies new signatures of selection in a deep sample of West African Plasmodium falciparum malaria parasites. Mol Biol Evol. 2012;29:3249–53.
    1. Nguitragool W, Bokhari A, Pillai A. Malaria parasite clag genes determine nutrient uptake channel activity on infected red blood cells. Cell. 2011;145:665–77.
    1. Van Tyne D, Park DJ, Schaffner SF, et al. Identification and functional validation of the novel antimalarial resistance locus PF10_0355 in Plasmodium falciparum. PLoS Genet. 2011;7:e1001383.
    1. Ariey F, Witkowski B, Amaratunga C, et al. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature. 2014;505:50–5.
    1. Amambua-Ngwa A, Tetteh KKA, Manske M, et al. Population genomic scan for candidate signatures of balancing selection to guide antigen characterization in malaria parasites. PLoS Genet. 2012;8:e1002992.
    1. Ochola LI, Tetteh KKA, Stewart LB, Riitho V, Marsh K, Conway DJ. Allele frequency–based and polymorphism-versus-divergence indices of balancing selection in a new filtered set of polymorphic genes in Plasmodium falciparum. Mol Biol. 2010;27:2344–51.
    1. Laufer M, Thesing P, Eddington N, et al. Return of Chloroquine Antimalarial Efficacy in Malawi. N Engl J Med. 2006;355:1959–66.
    1. Nair S, Miller B, Barends M, et al. Adaptive copy number evolution in malaria parasites. PLoS Genet. 2008;4:e1000243.
    1. Ejigiri I, Ragheb DRT, Pino P, et al. Shedding of TRAP by a rhomboid protease from the malaria sporozoite surface is essential for gliding motility and sporozoite infectivity. PLoS Pathog. 2012;8:e1002725.
    1. Conway DJ, Fanello C, Lloyd JM, et al. Origin of Plasmodium falciparum malaria is traced by mitochondrial DNA. Mol Biochem Parasitol. 2000;111:163–71.
    1. Vaidya AB, Mather MW. Mitochondrial evolution and functions in malaria parasites. Annu Rev Microbiol. 2009;63:249–67.
    1. Nkhoma S, Molyneux M, Ward S. Molecular surveillance for drug-resistant Plasmodium falciparum malaria in Malawi. Acta Trop. 2007;102:138–42.
    1. Mwai L, Ochong E, Abdirahman A, et al. Chloroquine resistance before and after its withdrawal in Kenya. Malar J. 2009;8:106.
    1. Frosch AEP, Laufer MK, Mathanga DP, et al. Return of widespread chloroquine-sensitive Plasmodium falciparum to Malawi. J Infect Dis. 2014;210:1110–4.
    1. Setthaudom C, Tan-ariya P, Sitthichot N, et al. Role of Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes on in vitro chloroquine resistance in isolates of Plasmodium falciparum from Thailand. Am J Trop Med Hyg. 2011;85:606–11.
    1. Mobegi VA, Duffy CW, Amambua-Ngwa A, et al. Genome-wide analysis of selection on the malaria parasite Plasmodium falciparum in West African populations of differing infection endemicity. Mol Biol Evol. 2014;31:1490–9.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir