Hemochromatosis: An Evolutionary Advantage? -

by Annika Bright 

Hemochromatosis is a recessive genetic disorder characterised by an excess concentration of Ferritin (an “iron-locking” protein) in the blood and is caused by a genetic mutation in the HFE gene on chromosome six. Moreover, during orderly function the HFE gene is largely responsible for modulating the levels of iron absorbed. However with the occurrence of the HFE mutation resulting from the gain of two recessive mutated, alleles, (for example, the more severe, C282Y variant) the person will develop symptoms. In order to understand this further, it would be useful to indicate how the penetrance of the C282Y variant results in the disease’s development. As a result of the C282Y mutation, less of the protein, Hepcidin is produced which has the function of regulating the absorption of iron through the transmembrane carrier protein, Ferroportin. Therefore, less Hepcidin results in continuous iron absorption. The disorder presents itself with various detrimental complications including iron deposits in joints, leading to arthritis as well as deposits in the heart tissue causing arrhythmia (abnormal heart rhythms). 

Interestingly, it has been identified that the existence of Hemochromatosis may have been an evolutionary advantage as stated in ‘Survival of the Sickest’ by Dr Moalem. Specifically mentioned in the book was the idea of its relationship with the Bubonic plague. It was stated that in the appearance of Hemochromatosis, a constant “iron-locking” - due to the overload of iron - occurs and the previously-mentioned protein, Ferritin carries out this function. Despite there being excess iron present, the macrophage (a category of white blood cell) is not available to this iron. Thus in normal circumstances, as its function is to engulf pathogens - such as bacteria - by phagocytosis and eliminate these using lysozymes (hydrolytic enzymes which destroy the pathogen) macrophages are often subverted by the bacteria as it feeds off the iron in the macrophage. Conversely, in Hemochromatosis, the macrophages lack iron and therefore, pathogens like bacteria are unable to use macrophages to survive and reproduce. So, are more effective in the elimination of pathogens. In regards to the Bubonic plague, those who had two copies of the HFE mutation (Hemochromatosis) had a more effective macrophage immune response so could withstand the infection of the bacterium Yersinia Pestis. This bacterium was responsible for the symptoms of the plague. As a result, those with Hemochromatosis were more likely to survive, reproduce and pass this allele to their offspring. In conclusion, at the time of the Bubonic plague, Hemochromatosis served as an evolutionary advantage and therefore this mutation continued to appear in the gene pool. 

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