Malarial Resistance and Susceptibility, Genetics of


Resistance to malaria in humans, as well as drug and insecticide resistance by the malarial parasite and the mosquito that acts as its vector, respectively, is the result of adaptation by all three organisms. Characterization of the function and evolution of the genes underlying this resistance and susceptibility is paramount to our understanding of malarial treatment and eradication.

Keywords: malaria; plasmodium; anopheles; anemia; parasite

Figure 1.

Global percentages of children with malarial infections. Although several geographic areas of South America, India, Southeast Asia and Australasia have frequencies of malaria that range from 10% to 50%, sub‐Saharan Africa is most afflicted with frequencies >50% in many regions.

Figure 2.

Dateline for malarial drugs and subsequent Plasmodium resistance. Variation in parasite resistance (R) ranges from an almost immediate response, as in pyrimethamine (Pyr)–sulfadoxine (SDX), to decades later, with different geographic regions often taking longer than others as in chloroquine (CQ). Other drugs are proguanil (PG), artemisinin (Art), mefloquine (Mef), halofantrine (Hal), atovaquone (Ato), chlorproguanil and dapsone (LD) (Hyde, ).



Aitman TJ, Cooper LD, Norsworthy PJ et al. (2000) Malaria susceptibility and CD36 mutation. Nature 405: 1015–1016.

Annan Z, Durand P, Ayala FJ et al. (2007) Population genetic structure of Plasmodium falciparum in the two main African vectors, Anopheles gambiae and Anopheles funestus. Proceedings of the National Academy of Sciences of the USA 104: 7987–7992.

Ayodo G, Price AL, Keinan A et al. (2007) Combining evidence of natural selection with association analysis increases power to detect malaria‐resistance variants. American Journal of Human Genetics 81: 234–242.

Barry AE, Leliwa‐Sytek A, Tavul L et al. (2007) Population genomics of the immune evasion (var) genes of Plasmodium falciparum. PLoS Pathology 3: e34.

Donnelly MJ, Licht MC and Lehmann T (2001) Evidence for recent population expansion in the evolutionary history of the malaria vectors Anopheles arabiensis and Anopheles gambiae. Molecular Biology and Evolution 18: 1353–1364.

Fairhurst RM, Baruch DI, Brittain NJ et al. (2005) Abnormal display of PfEMP‐1 on erythrocytes carrying haemoglobin C may protect against malaria. Nature 435: 1117–1121.

Gardner MJ, Hall N, Fung E et al. (2002) Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419: 498–511.

Hamblin MT, Thompson EE and Di Rienzo A (2002) Complex signatures of natural selection at the Duffy blood group locus. American Journal of Human Genetics 70: 369–383.

Hanchard N, Elzein A, Trafford C et al. (2007) Classical beta‐globin sickle haplotypes exhibit a high degree of long‐range haplotype similarity in African and Afro‐Caribbean populations. BMC Genetics 8: 52.

Herrera S, Corradin G and Arévalo‐Herrera M (2007) An update on the search for a Plasmodium vivax vaccine. Trends in Parasitology 23: 122–128.

Holt RA, Subramanian GM, Halpern A et al. (2002) The genome sequence of the malaria mosquito Anopheles gambiae. Science 298: 129–149.

Hughes AL and Verra F (2001) Very large long‐term effective population size in the virulent human malaria parasite Plasmodium falciparum. Proceedings of the Royal Society of London. Series B: Biological Sciences 268: 1855–1860.

Hyde JE (2005) Drug‐resistant malaria. Trends in Parasitology 21: 494–498.

Jeffares DC, Pain A, Berry A et al. (2007) Genome variation and evolution of the malaria parasite Plasmodium falciparum. Nature Genetics 39: 120–125.

McCollum AM, Poe AC, Hamel M et al. (2006) Antifolate resistance in Plasmodium falciparum: multiple origins and identification of novel dhfr alleles. Journal of Infectious Disease 194: 189–197.

Muller P, Donnelly MJ and Ranson H (2007) Transcription profiling of a recently colonised pyrethroid resistant Anopheles gambiae strain from Ghana. BMC Genomics 8: 36.

Ohashi J, Naka I, Patarapotikul J et al. (2004) Extended linkage disequilibrium surrounding the hemoglobin E variant due to malarial selection. American Journal of Human Genetics 74: 1198–1208.

Pasvol G, Wainscoat JS and Weatherall DJ (1982) Erythrocytes deficient in glycophorin resist invasion by the malarial parasite Plasmodium falciparum. Nature 297: 64–66.

Patel SS, Mehlotra RK, Kastens W et al. (2001) The association of the glycophorin C exon 3 deletion with ovalocytosis and malaria susceptibility in the Wosera, Papua New Guinea. Blood 98: 3489–3491.

Ranson H, Jensen B, Vulule JM et al. (2000) Identification of a point mutation in the voltage‐gated sodium channel gene of Kenyan Anopheles gambiae associated with resistance to DDT and pyrethroids. Insect Molecular Biology 9: 491–497.

Riehle MM, Markianos K, Niare O et al. (2006) Natural malaria infection in Anopheles gambiae is regulated by a single genomic control region. Science 312: 577–579.

Tishkoff SA and Verrelli BC (2003) Patterns of human genetic diversity: implications for human evolutionary history and disease. Annual Review of Genomics and Human Genetics 4: 293–340.

Tishkoff SA and Verrelli BC (2004) G6PD deficiency and malarial resistance in humans: insights from evolutionary genetic analyses. In: Dronamraju K (ed.) Infectious Disease: Host–Pathogen Evolution. New York: Cambridge University Press.

Verrelli BC, Tishkoff SA, Stone AC and Touchman JW (2006) Contrasting histories of G6PD molecular evolution and malarial resistance in humans and chimpanzees. Molecular Biology and Evolution 23: 1592–1601.

Wootton JC, Feng X, Ferdig MT et al. (2002) Genetic diversity and chloroquine selective sweeps in Plasmodium falciparum. Nature 418: 320–323.

Further Reading

Cogswell F (1992) The hypnozoite and relapse in primate malaria. Clinical Microbiology Reviews 5: 26–35.

Ekland EH and Fidock DA (2007) Advances in understanding the genetic basis of antimalarial drug resistance. Current Opinion in Microbiology 10: 363–370.

Kwiatkowski DP (2005) How malaria has affected the human genome and what human genetics can teach us about malaria. American Journal of Human Genetics 77: 171–192.

Williams TN (2006) Human red blood cell polymorphisms and malaria. Current Opinion in Microbiology 9: 388–394.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Verrelli, Brian C(Jul 2008) Malarial Resistance and Susceptibility, Genetics of. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020766]