KEY WORDSlinked genetic traits, Membrane bound hemoglobin Oxidative stress, falciparum malaria, Malaria- ABSTRACTThis paper focuses on the interaction between oxidized hemoglobin and the erythrocyte membrane, and its relevance to some falciparum malaria-linked genetic traits. We first present the experimental evidence which suggests that the interaction between hemoglobin derivatives and membrane proteins is an important cellular mechanism for the erythrocytes carrying HbS, HbE, HbF, a-and P-thalassemia, and GGPD deficiency. Thereafter, we show how the Hblmembrane interaction might act as primum movens for diverse cellular mechanisms which 1) reduce invasion of erythrocytes by the falciparum parasite; 2) impair parasite survival and development within the cell; 3) accelerate infected erythrocyte clearance by phagocytosis. We claim that oxidative stress is the driving force of this process, since highly reactive species (like 0,-and H202) mediate the gradual oxidation of Hb to irreversible hemichrome-containing Heinz bodies. We therefore suggest that positing the interaction between oxidized hemoglobin and cell membrane as a common basis for several falciparum malaria-linked genetic traits is not only consistent with experimental evidence gathered so far, but provides a new, clearer perspective: the molecular event on which these known protective traits rest. In the last part of the paper we will discuss two case studies which provide further support for the role played by hemoglobin derivatives and membrane proteins: 1) the influence of a cyanogen-rich diet on the distribution of HbPV gene frequencies in Liberia (Jackson [1990] Am.

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Ten protein coding loci (6-PGD, A1-AT, ACP1, CaII, ESD, GC, GPX1, Hb beta, PGM1, and TF) were analyzed in the Mbenzele Pygmies from the Central African Republic. The frequency data were used to calculate the genetic distances between Mbenzele Pygmies and other African groups. In the principal coordinate plot of FST genetic distances, the Mbenzele cluster together with other Pygmies of the western cluster, the Biaka from C.A.R., Gielli from Cameroon, and Babinga from Congo. By contrast, they are considerably distanced from other Pygmy groups of the eastern cluster (Twa from Rwanda, Mbuti from Zaire). Genetic distances obtained using protein loci were compared with those based on microsatellite loci. The two distance matrices are insignificantly correlated (r = 0.268; one tail probability = 0.332), and the main difference is in the higher genetic affinity between the Mbenzele and Biaka Pygmies observed at the protein level. Although reasons underlying the discrepancy between inter-populational variation at protein and DNA loci are not established with certainty, the comparison suggests that the genetic distance between the Mbenzele and Biaka Pygmies at microsatellite loci could have been shaped by genetic drift.

This paper focuses on the interaction between oxidized hemoglobin and the erythrocyte membrane, and its relevance to some falciparum malaria‐linked genetic traits. We first present the experimental evidence which suggests that the interaction between hemoglobin derivatives and membrane proteins is an important cellular mechanism for the erythrocytes carrying HbS, HbE, HbF, α‐ and β‐thalassemia, and G6PD deficiency. Thereafter, we show how the Hb/membrane interaction might act as primum movens for diverse cellular mechanisms which 1) reduce invasion of erythrocytes by the falciparum parasite; 2) impair parasite survival and development within the cell; 3) accelerate infected erythrocyte clearance by phagocytosis. We claim that oxidative stress is the driving force of this process, since highly reactive species (like O2− and H2O2) mediate the gradual oxidation of Hb to irreversible hemichrome‐containing Heinz bodies. We therefore suggest that positing the interaction between oxidized hemoglobin and cell membrane as a common basis for several falciparum malaria‐linked genetic traits is not only consistent with experimental evidence gathered so far, but provides a new, clearer perspective: the molecular event on which these known protective traits rest. In the last part of the paper we will discuss two case studies which provide further support for the role played by hemoglobin derivatives and membrane proteins: 1) the influence of a cyanogen‐rich diet on the distribution of Hbβ*S gene frequencies in Liberia (Jackson [1990] Am. J. Hum. Biol. 2:521–532); and 2) population data on polymorphisms at the Hbβ and GPXI loci (Destro‐Bisol and Spedini [1989] Am. J. Phys. Anthropol. 79:217–224). © 1996 Wiley‐Liss, Inc.

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