Two evolutionary models for the interactions of dietary organic cyanogens, hemoglobins, and falciparum malaria

Abstract

Significant regional and ethnic variations in hemoglobin S frequencies among 485 adult nonpregnant Liberian women uniformly exposed to holoendemic falciparum malaria suggest that an additional major factor may influence the distribution of this hemoglobinopathy and the severity of the infectious disease with which it is causally associated. The differential consumption of organic cyanogen-rich cassava (Manihot esculenta) foodstuffs and subsequent dosage-dependent in vivo exposure to sublethal CN , SCN , and CNO may directly interact with hemoglobin S by inhibiting sickling diathesis, and, at higher intakes, this dietary factor may adversely affect Plasmodium survival and antigenicity. In this study, low dietary organic cyanogen intakes (0.3 mg CN /kg body wt/day) in NW and W geographical areas are associated with higher regional hemoglobin S gene frequencies (11%; phenotypic incidence 20%), lower mean (± SD) positive Plasmodium antibody titers (861.6 ± 102.4), and a higher mean (± SEM) prevalence of clinical falciparum malaria [3.04 times (± 0.09) within the previous 12 months]. In contrast, high dietary organic cyanogen intakes (1.5 mg CN /kg body wt/day in SE and C geographical areas) are associated with lower hemoglobin S gene frequencies (2%; phenotypic incidence 4%), higher mean (± SD) positive Plasmodium antibody titers (968.7 ± 160.5), and a lower mean (± SEM) prevalence of clinical falciparum malaria [1.73 times (± 0.11) within the previous 12 months]. No other significant malaria-linked genetic variation exists between regions or ethnic groups. Two evolutionary models are hypothesized to suggest how 18 generations of differential dietary organic cyanogen intakes could produce two distinct patterns of change in hemoglobin S gene frequencies, modifying both the cadence and direction of evolution.

Millipedes as Food for Humans: Their Nutritional and Possible Antimalarial Value—A First Report

“…Natural benzoquinones are known to exert an antiplasmodic activity in vitro [69], and their metabolites might act as systemic repellents against mosquitoes or as antimalarial prophylaxis in the Bobos. Moreover, studies on West African populations have demonstrated strong links between malaria, sub-lethal cyanide intake from bitter cassava, and sickle-cell anemia [60, 70], a genetic pathology affecting erythrocytes that confers protection against Plasmodium . Thus, after demonstrating that cyanide interacts with hemoglobins, partially compensating sickle-cell dysfunctionality [60, 71], some authors proposed that the abundant consumption of bitter foods could enhance biological fitness in West African populations exposed to malaria [62, 70].…”

“…Moreover, studies on West African populations have demonstrated strong links between malaria, sub-lethal cyanide intake from bitter cassava, and sickle-cell anemia [60, 70], a genetic pathology affecting erythrocytes that confers protection against Plasmodium . Thus, after demonstrating that cyanide interacts with hemoglobins, partially compensating sickle-cell dysfunctionality [60, 71], some authors proposed that the abundant consumption of bitter foods could enhance biological fitness in West African populations exposed to malaria [62, 70]. Therefore, both ethological and bioanthropological evidences suggest that “toxic” millipedes consumed by the Bobo people take part in a complex biocultural mechanism for malaria control.…”

African Genetic Diversity: Implications for Human Demographic History, Modern Human Origins, and Complex Disease Mapping

“…Although the variant driving the signal of positive selection was not conclusively determined, the authors speculated that differential selection in malarial (favoring the K variant) and nonmalarial (favoring the N variant) environments has maintained both alleles at relatively high frequencies in Africa. An earlier study suggested that the higher dietary intake of naturally occurring bitter substances, such as organic cyanogens, may be protective against malarial infection in populations from Central and Southeast Africa (91]]). Additionally, an inhibitory effect of cyanide on the normal development of the P. falciparum parasite has been observed in vitro (137a]).…”

Interaction between oxidized hemoglobin and the cell membrane: A common basis for several falciparum malaria‐linked genetic traits

“…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.…”

“…In the last part of the paper we will discuss two case studies which can provide further support to the role played by hemoglobin derivatives and membrane proteins: 1) the influence of sublethal cyanogens included in the diet on the distribution of Hbp*S gene frequencies in Liberia (Jackson, 1990); 2) population data on polymorphisms at the HbP and GPXl loci (Destro-Bisol and Spedini, 1989).…”