Abstract
Main objective of this article is to review and evaluate recent red cell variant studies for protection against malaria and natural selection. Malaria is a parasitic disease highly widespread in tropical and subtropical regions of the world. It is also one of the leading causes of death worldwide and genes involved in malaria resistance are the most important for natural selection in human populations. Multiple red cell variants, which evolved probably to counter the lethal effects of malaria and confer protection against malaria through different mechanisms, show high frequencies in malaria endemic vulnerable populations. Different natural protective/resistance mechanisms including hampering of parasite growth, invasion related immunological responses or rapidly elimination of malaria parasite from the infected erythrocytes of host have briefly been discussed, evaluated, and reviewed. Conclusions drawn have been projected here. High frequency of inherited hemoglobin disorders including thalassemias, and red cell G6PD enzyme deficiency, which seemed to evolve simultaneously in relation to malaria, and high mortality caused by Plasmodium falciparum malaria in different vulnerable populations of tropical and subtropical parts of world, confirm that the natural selection is certainly operating against malaria in one way or another; and human population genetics have distinctly played a significant role in the co-evolution of host and malaria. The inverse relationship between sickle cell trait and G6PD deficiency and vice versa, revealed by allele frequencies distribution shown in our previous studies, is a testimony of disequilibrium, as sickle cell allele being replaced by G6PD deficiency allele in populations of central India. Positive natural selection plays a definite role against malaria for maintaining balance in high frequency endemic populations.
Highlights
There is a need to recognize and respect the fact that each person is a unique in this world with its gifted qualities and genetic endowments
High frequency of inherited hemoglobin disorders including thalassemias, and red cell G6PD enzyme deficiency, which seemed to evolve simultaneously in relation to malaria, an d high mortality caused by Plasmodium falciparum malaria in different vulnerable populations of tropical and subtropical parts of world, confirm that the natural selection is certainly operating against malaria in one way or another; and human population genetics have distinctly played a significant role in the co-evolution of host and malaria
The inverse relationship between sickle cell trait and G6PD deficiency and vice versa, revealed by allele frequencies distribution shown in our previous studies, is a testimony of disequilibrium, as sickle cell allele being replaced by G6PD deficiency allele in populations of central India
Summary
There is a need to recognize and respect the fact that each person is a unique in this world with its gifted qualities and genetic endowments. It seems that different abnormal hemoglobin variants (C,D,E,F,S and thalassemias) and G6PD enzyme deficiency are the directed mutations against the malaria malady as the heterozygotes or carriers of these genetic traits do not suffer severely from the dreadful malaria (Tables 1-4) Another important factor is the relatively high frequency of consanguineous marriages in many regions of India with high frequency of these red cell genetic variants; this mechanism has an important effect on increasing the gene frequency of the fore said recessively inherited disorders in vulnerable populations of central India [50,51]. It affects about 1/10 African American males in United States [17,41]
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