Haldane's Hypothesis Research Articles

Non-nutritional anemia: Malaria, thalassemia, G6PD deficiency and tuberculosis in Indonesia.

Anemia affects people worldwide and results in increased morbidity and mortality, particularly in children and reproductive-age women. Anemia is caused by an imbalance between red blood cell (RBC) loss and production (erythropoiesis), which can be caused by not only nutritional factors but also non-nutritional factors, such as inflammation and genetics. Understanding the complex and varied etiology of anemia is crucial for developing effective interventions and monitoring anemia control programs. This review focusses on two interrelated nonnutritional causes of anemia: malaria infection and RBC disorders (thalassemia and G6PD deficiency), as well as tuberculosis. According to the Haldane hypothesis, thalassemia occurs as a protective trait toward malaria infection, whereas G6PDd arises in malaria-endemic regions because of positive selection. Indonesia is a malariaendemic region; thus, the frequency of thalassemia and G6PD deficiency is high, which contributes to a greater risk for non-nutritional anemia. As Indonesia is the second global contributor to the newly diagnosed tuberculosis, and active pulmonary tuberculosis patients are more anemic, tuberculosis is also contributes to the increasing risk of anemia. Therefore, to reduce anemia rates in Indonesia, authorities must consider non-nutritional causes that might influence the local incidence of anemia, and apply co-management of endemic infectious disease such as malaria and tuberculosis, and of genetic disease i.e. thalassemia and G6PDd.

Non-nutritional anemia: Malaria, thalassemia, G6PD deficiency and tuberculosis in Indonesia.

Anemia affects people worldwide and results in increased morbidity and mortality, particularly in children and reproductive-age women. Anemia is caused by an imbalance between red blood cell (RBC) loss and production (erythropoiesis), which can be caused by not only nutritional factors but also non-nutritional factors, such as inflammation and genetics. Understanding the complex and varied etiology of anemia is crucial for developing effective interventions and monitoring anemia control programs. This review focusses on two interrelated nonnutritional causes of anemia: malaria infection and RBC disorders (thalassemia and G6PD deficiency), as well as tuberculosis. According to the Haldane hypothesis, thalassemia occurs as a protective trait toward malaria infection, whereas G6PDd arises in malaria-endemic regions because of positive selection. Indonesia is a malariaendemic region; thus, the frequency of thalassemia and G6PD deficiency is high, which contributes to a greater risk for non-nutritional anemia. As Indonesia is the second global contributor to the newly diagnosed tuberculosis, and active pulmonary tuberculosis patients are more anemic, tuberculosis is also contributes to the increasing risk of anemia. Therefore, to reduce anemia rates in Indonesia, authorities must consider non-nutritional causes that might influence the local incidence of anemia, and apply co-management of endemic infectious disease such as malaria and tuberculosis, and of genetic disease i.e. thalassemia and G6PDd.

Fine Temporal Mapping of Plasmodium Falciparum growth Inhibition in Hypoxic Sickle Cell Trait Erythrocytes

Background: Despite the global acceptance of Haldane's hypothesis that individuals with sickle cell trait (AS) are protected against malaria, an exact mechanism of resistance remains unknown. Several theories to explain the resistance such as increased splenic destruction, impaired hemoglobin digestion, reduced cytoadherence and specific translocation of host specific microRNAs have been proposed. Here we carefully examine the influence of hypoxia and its relation to parasite cytoadherence and growth in AS and normal (AA) human red blood cells (RBCs).Materials and Methods: To assess the influence of oxygen tension on parasite proliferation in AS RBCs, we followed the proliferation of tightly synchronized P. falciparum within AS and AA RBCs at 1, 5, 10, and 17% oxygen by flow cytometry and microscopy. Carbon monoxide (CO) studies were performed by introducing 100% CO gas into our enclosed chamber system every 21 hours to prevent sickling at low oxygen.Results: Flow cytometry assessment of DNA content confirms the absence of DNA replication within parasites in AS erythrocytes at low oxygen, however normal DNA replication is observed in the presence of high oxygen tension and when CO is introduced at low oxygen. Moving parasites from high to low oxygen tension greatly influences the extent of parasite maturity; parasites moved at 16 and 20 hours post invasion (hpi) do not mature beyond that of the late ring/early trophozoite stage while parasites moved at 24, 28, and 32 hpi develop increasingly more merozoites.Conclusion: Here, we show that in hypoxic conditions parasites in AS erythrocytes stall at the late ring/early trophozoite stage and do not replicate their DNA. We also show that treatment of AS erythrocytes with high oxygen tension or carbon monoxide, a potent inhibitor of sickle hemoglobin polymerization, reverses this phenotype. We propose that the mechanism of AS protection is largely due to P.falciparum's inability to digest polymerized sickle hemoglobin once the parasite sequesters in the hypoxic microvasculature. This is likely a key driver of the reduced parasite densities observed in actual infections in AS individuals. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Antagonistic coevolution with parasites maintains host genetic diversity: an experimental test

Genetic variation in natural populations is a prime prerequisite allowing populations to respond to selection, but is under constant threat from forces that tend to reduce it, such as genetic drift and many types of selection. Haldane emphasized the potential importance of parasites as a driving force of genetic diversity. His theory has been taken for granted ever since, but despite numerous studies showing correlations between genetic diversity and parasitism, Haldane's hypothesis has rarely been tested experimentally for unambiguous support. We experimentally staged antagonistic coevolution between the host Tribolium castaneum and its natural microsporidian parasite, Nosema whitei, to test for the relative importance of two separate evolutionary forces (drift and parasite-induced selection) on the maintenance of genetic variation. Our results demonstrate that coevolution with parasites indeed counteracts drift as coevolving populations had significantly higher levels of heterozygosity and allelic diversity. Genetic drift remained a strong force, strongly reducing genetic variation and increasing genetic differentiation in small populations. To our surprise, differentiation between the evolving populations was smaller when they coevolved with parasites, suggesting parallel balancing selection. Hence, our results experimentally vindicate Haldane's original hypothesis 60 years after its conception.

Experimental validation of Haldane's hypothesis on the role of infection as an evolutionary force for Metazoans

A common drawback in evolutionary science is the fact that the evolution of organisms occurs in geological timing, completely out of the time scale of laboratory experimental work. For this reason, some relevant hypotheses on evolution of Metazoans are based on correlations more than on experimental data obtained for testing the robustness of those hypotheses. In the current work, we implement an experimental methodology to analyze the role of infections as a driving force in the evolution of Metazoans (Haldane's hypothesis). To that goal, we have used simple models of virulence with short reproduction times, large populations, and that are easily testable in the laboratory. Using the bacteriovirus nematode Caenorhabditis elegans as a model organism under evolution and their infection by the environmental opportunistic bacterial pathogen Pseudomonas aeruginosa as the selective force, we have demonstrated that bacterial infection selects an evolved nematode lineage resistant to infection, with changes in its respiration and capability of consuming novel food resources. Using an experimental approach, we show that infection is a selective force in the evolution of Metazoans as proposed earlier by Haldane.

Breakdown of Luttinger liquid state in a one-dimensional frustrated spinless fermion model

The Haldane hypothesis about the universality of the Luttinger liquid (LL) behavior in conducting one-dimensional fermion systems is checked numerically for the spinless fermion model with next-nearest-neighbor interactions. It is shown that for the large enough interactions the ground state can be gapless due to frustrations but at the same time might not belong to the same universality class as a simple LL. The exponents of the correlation functions for this unusual conducting state are found numerically by a finite-size method.

Past malaria, thalassemia and woman fertility in southern Italy

The role of natural selection in maintaining the thalassemia polymorphism is examined in a southern Italy district, in the past affected by malaria endemia. The Haldane's hypothesis that the thalassemia heterozygotes enjoy more protection than the normal homozygotes against the risk of malaria infection, seems to be confirmed by this indirect study at population level. The higher number of children born of the women who lived in the highly endemic villages, where the highest proportion of heterozygotes occurs, supports the hypothesis that the woman fertility contributes to the thalassemia maintenance. The joint effects of the acquired and inherited immunities and of the reproductive compensation are assumed as the mechanisms through which malaria and thalassemia influence fertility.

Are reference limits for serum creatine kinase valid in detection of the carrier state for Duchenne muscular dystrophy?

We evaluated serum creatine kinase (CK) as an index to heterozygosity in Duchenne muscular dystrophy. When the 97.5th percentile of the CK normal reference interval was selected as the cutoff point, only 31% of 28 obligate carrier mothers and 24% of 43 mothers of simplex cases (those with only one occurrence of dystrophy in the kindred) exceeded this cutoff value. The outcome depended to some degree on the method used for establishing the reference limit for 379 presumably non-carrier, ambulatory women. The considerable overlap of CK activities between the control and carrier population as well as the non-gaussian distribution of the data permitted no satisfactory approach for differentiating these two populations. Neither the application of likelihood ratios, which evaluates a continuum of results without the dichotomy of a cutoff point, nor the application of predictive value based on sensitivity and specificity, which involves use of a cutoff value for decision making, provided a reliable estimate of carrier status. There was no significant difference (2 alpha = .19) between the median CK activity of obligate carrier mothers and mothers of simplex cases. The serum CK test does not provide data that either support or reject the Haldane hypothesis.

A protective function of the coacervates against UV light on the primitive Earth

Results from simulation experiments in the laboratory support the Oparin–Haldane hypothesis of chemical evolution1–4. The organic compounds produced may have accumulated in the primitive sea, constituting the so-called ‘primordial soup’ of organic molecules. Beyond this primordial stage, however, many developments were required before the emergence of the first cellular organism. The first cell need not necessarily have been a modern cell, complete with a membrane, a chromosome, ribosomes, enzymes, a metabolism, and the property of self-replication; the primary requirement of the protocell would have been the ability to evolve into a complete cell. There are many models of the protocell: for example coacervate droplets5–9, proteinoid microspheres10,11, micelles (lipid vesicles)12, and marigranules13,14. Of these, the coacervate droplets are of interest as they are dynamic6,7 and because their mechanism of formation is perhaps better understood15–16. Coacervate droplets are essentially small bounded spaces in which the concentration of substances is higher than in the surrounding medium and in which the distribution of the substances differs from that in the solutions. Their essential functions in the protocell model are: (1) selection; (2) concentration; (3) production of hypohydrous effects; (4) interaction; and (5) organization5–9. Here we report another possible function of the coacervate. We added glycine or diglycine to the coacervate system, then irradiated the system with an argon lamp. We report that the coacervate droplets concentrated glycine or diglycine, thus protecting them from decomposition by irradiation. These results suggest a protective function of the coacervate against UV light on the primitive Earth.

Thiocyanate in Red Sea brine and its implications

THE Oparin–Haldane hypothesis about the origin of life has provided a rational theoretical model for laboratory research. Almost thirty years of experiments have supported this hypothesis. Verification of the hypothesis in terrestrial environments, however, has not been documented. Some environments such as thermal springs in the Kuril Islands have been reported to have possible chemical precursors but lack of sterility and other factors have not made it possible to establish evidence for natural, terrestrial abiotic synthesis1. We identify here the Atlantis II Deep brine as a promising site for searching for chemical precursors, report finding thiocyanate in the brine and suggest a relationship between chemical evolution and the evolution of the Earth's crust.

Gene segregation in autotetraploids. II

Three main theories of autotetraploid segregation have been propounded, the Muller hypothesis based on the random assortment of chromosomes at meiosis, the Haldane hypothesis based on the random assortment of chromatids, and the Mather hypothesis in which the ratios are considered to be not fixed but varying according to the amount of quadrivalent formation and the distance of a gene from the centromere. The first two hypotheses are special cases of the last, which is, in general, the most satisfactory for explaining observed data.

RESPIRATORY QUOTIENTS OF EXPIRED AND ALVEOLAR AIR AT NORMAL AND REDUCED BAROMETRIC PRESSURES

In the paper are reported the results of 55 experiments on four subjects seated quietly at ground level and 15,000 ft. breathing air. Inspiratory and expiratory alveolar air samples were taken immediately before and after a period during which expired air was collected.A systematic difference can be demonstrated between the respiratory quotients of inspiratory and expiratory samples of alveolar air taken when the subject is seated at rest. This difference is much diminished by anoxia at a barometric pressure equivalent to 15,000 ft. supporting Krogh and Lindhard's analysis of the course of gaseous exchanges in the lungs. The R.Q.'s of expiratory samples of alveolar air approximate closely those of expired air. Haldane's hypothesis that the respiratory dead space for carbon dioxide is smaller than for oxygen is not supported by our findings under seated resting conditions on the average. The R.Q. of expired air may be used for calculating average relations between the partial pressures of carbon dioxide and oxygen in alveolar air by the Alveolar Equation.

On the Nature of the Oxygen Linkage in Oxyhemoglobin

In order to test Haldane's hypothesis that oxygen exists in oxyhemoglobin as a peroxide compound, an attempt was made to identify hydrogen peroxide in solutions of the blood pigment which had been denatured by acid. If oxyhemoglobin is an iron peroxide, we should expect it to behave as do other metallic peroxides, by reacting with acids to form hydrogen peroxide. Inasmuch as the acid hematin resulting from such denaturation has little, if any, catalase activity, any hydrogen peroxide formed should persist in solution.Solutions of 10 millimolar human oxyhemoglobin were treated with 8 volumes of .04 molar sulphuric acid and then precipitated with 5 volumes of 2% phosphovanadic acid, the latter serving the double purpose of precipitating the protein and of indicating the presence of any peroxide that might be liberated. In every instance the test was negative. Using chromic acid in acetone solution as a test for hydrogen peroxide, none of the latter could be detected in the ordinary Folin-Wu filtrate from bl...