Evolution of alpha-Gal synthesis - a growing risk for alpha Gal syndrome

BACKGROUND: Alpha-Gal syndrome (AGS) is a growing burden worldwide associated with arthropods and allergies with pathologies such as urticaria, digestive and anaphylactic reactions. These reactions commonly appear 2-6 h after consumption of mammalian meat and derived pharmaceuticals mediated by immunoglobulin E against the oligosaccharide alpha-Gal epitope. OBJECTIVE: Despite the increasing incidence of AGS, it is underdiagnosed and requires information and initiatives to reduce disease risks and incidence while improving prevention and treatment. CONTENT: Our hypothesis is that Galactosyltransferase associated with alpha-Gal synthesis appeared and evolved in bacteria during the Mesoproterozoic Era ca. 1000 million years ago (Mya). Then, in Mollusca during the Cambrian and in Arthropoda and Mammalia during the Triassic period associated with improved fitness in organisms repopulating the Earth after Permian-Triassic Great Dying extinction event but affected Hominidae leading to catastrophic selection in the Oligocene. CONCLUSIONS: With global rapidly changing climate and population dynamics, it should be considered that multiple arthropod species evolved to synthesize alpha-Gal as a guidance to develop preventive and control measures to reduce the risks of exposure to AGS. Accordingly, research should focus on the role of other organisms in addition to ticks in the evaluation and prevention of risks associated with the AGS with education for patients and medical staff to improve prevention and management of patients with AGS.Key messagesThe alpha-Gal synthesis evolved across multiple Arthropoda, Mollusca and MammaliaHominids developed to produce anti-alpha-Gal antibodies with protective capacityAlpha-Gal syndrome (AGS) in humans is associated with arthropods and allergic reactionsOther organisms are potential overlooked sources of alpha-gal.