Evolutionary biological basis of Ashkenazi Lysosomal Storage Diseases: it’s all because of diet

Abstract

Abstract An age-old unanswered question that still puzzle evolutionary biologists, is: why do certain autosomal-recessive, lysosomal storages diseases (LSDs), such as, Tay-Sachs, Gaucher, etc. selectively afflict the Ashkenazim more than other Jewish groups and the general population? The most well-accepted theory of ‘population bottleneck and drift’ cannot answer, among other questions, why the Ashkenazim are susceptible to only animal-specific, sphingolipid-mediated LSDs but not to non-animal ones, since genetic drift should influence both animal and non-animal specific LSDs equally. Here, those unanswered questions are answered: Once hunter-gatherers in the Fertile Crescent became agriculturists some eleven-to-twelve millennia back, a dramatic change occurred to their diets. Their earlier low-carbohydrate diets were supplanted by grain-based, high-carbohydrate foods. From those early times, downstream through many millennia, higher consumption of grain-based carbohydrates also meant lower consumption of animal-derived sphingolipids, compared to their forager past. This resulted in selectional pressure in purging those specific enzymes in their cellular lysosomes that were necessary for breaking down complex animal-derived-sphingolipids into simpler lipids. During the past millennium, as the Ashkenazim moved from the Mideast to European locations, their consumption of animal-derived sphingolipid-rich-foods increased, because of the paucity and expense of plant-based, sphingolipid-rich-foods. However, because of missing animal-sphingolipid-specific lysosomal enzymes, those un-catabolized animal-derived-sphingolipids began accumulating/being-stored in their lysosomes, leading to LSDs, which is precisely the storage of those macromolecules in the lysosomes of cells. In contrast, other ethnic Jewish groups did not make such dramatic dietary changes over the past millennium, and hence they generally do not suffer from those LSDs either.