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Evolution of Genetic Resistance/Susceptibility to Malaria Infection

  1. Kanjaksha Ghosh1,
  2. Kinjalka Ghosh2

Published Online: 15 AUG 2012

DOI: 10.1002/9780470015902.a0022492

eLS

eLS

How to Cite

Ghosh, K. and Ghosh, K. 2012. Evolution of Genetic Resistance/Susceptibility to Malaria Infection. eLS. .

Author Information

  1. 1

    Indian Council of Medical Research, National Institute of Immunohaematology, Mumbai, India

  2. 2

    Indira Gandhi Government Medical College, Nagpur, India

Publication History

  1. Published Online: 15 AUG 2012

Abstract

Severe malaria infection still kills more than 2.7 million people across the globe every year. Of the few infections which has shaped human genome over the millennia through the process of natural selection, malaria infection has left its imprints on human genome. Genetic studies on malarial resistance started in the late 1940s with demonstration of protection against malaria in carriers of several haemoglobinopathy genes and further demonstration of increasing prevalence of such genes across the malarious areas of the world. As malaria parasites pass a significant period of its life inside the red cell, many red cell proteins and their genes were studied for polymorphic variants which offers protection against such infection. Total absence of Plasmodium vivax malaria in Western Africa and its linkage with total absence of red cell Duffy antigen is a case in point. Subsequently as a rational extension of the above idea, association of resistance or susceptibility to severe malarial infection were studied with relation to genes of innate immunity, adoptive immunity, cytokine genes, adhesion molecules, coagulation proteins, proteins involved in systemic inflammatory reactions etc. Innumerable studies have shown various kinds of association. However, at present the interest has shifted towards genome wide association studies with malarial infection. Present review stops short of genome wide association and presents a snapshot view of genome association with malaria infection.

Key Concepts:

  • The immune system of man has evolved to fight pathogens like malaria parasite.

  • Pathogens have exerted intense selective pressures on the evolution of the immune system of man.

  • Key elements of the adaptive immune system, such as antigen receptors and major histocompatibility complex molecules, show evidence of such selective pressures.

  • Mutation is the key genetic mechanism underlying the co-evolution of the immune system and pathogens.

  • Evolutionary adaptation to malaria involves many more aspects than modification of adoptive and Innate Immune system.

  • Owing to complex life cycle of the parasite and its specific requirements of nutrition and need for protection during its growth, the parasite vulnerability increases due to changes in Nutrient (haemoglobin), Host Enzyme system (Oxidant damage), changes in specialised receptors for entry into cells (Red cells, Hepatocytes) and its ability to adhere to Key cells (Endothelium).

  • Product of metabolism of malaria parasite (Hemozoin) exerts strong immunomodulatory effect.

  • As malaria parasite from different regions of the world exerted selection pressure on different population groups with different genetic endowment (polymorphisms), this resulted in evolution of different key resistant molecules against malaria in different parts of the world.

Keywords:

  • falciparum malaria;
  • vivax malaria;
  • red cell;
  • haemoglobin;
  • polymorphisms;
  • HLA antigens;
  • cytokine genes;
  • adhesion molecules;
  • endothelial cells;
  • toll like receptors;
  • haemozoin;
  • immunomodulation