The origin of dystrophin-glycoprotein complex(DGC)-related muscular dystrophies: the need for protection against an ancestral pathogen?

Abstract

Because of its crucial role during the early stages of morphogenesis, no genetic defects associated to dystroglycan have been reported so far. Dystroglycan is an important member of the dystrophin-glycoprotein complex (DGC) and in several muscular dystrophies, depending on abnormalities of proteins belonging to or associated with the DGC, it is frequently observed a significant reduction of dystroglycan levels at the sarcolemma. Recently, it has been demonstrated that dystroglycan acts as a receptor for pathogens such as M. leprae and arenaviruses. It is well-known that mutated alleles causing diseases can be selected in order to confer an additional genetic advantage. Herein it is discussed the possibility that mutations leading to a certain number of muscular dystrophies might have been originally selected to indirectly gain a specific advantage: the absence or the lower levels of dystroglycan could have greatly reduced the risk of some ancestral lethal infections specifically directed against muscles.