Evolution of Uric Acid Metabolism in Humans

Abstract Several evolutionary changes have led to uric acid levels being much higher in humans than in other mammals. Uric acid is the end product of purine metabolism in hominoids, including humans, due to the genetic loss of uricase activity during the Miocene epoch, and this is the main cause of the increased uric acid in hominoids. Additional factors that have contributed to increased levels of uric acid are the high renal tubular reabsorption of uric acid and the previous loss of the ability to synthesise vitamin C in hominoids. Several hypotheses have been proposed on the evolutionary advantage of increased serum uric acid levels in hominoids, although the biological reasons for this increase remain unclear. The large current increase in uric acid levels in humans in developed countries is mainly influenced by dietary factors and lifestyle changes. Key Concepts: Uric acid (UA) is the end product of purine metabolism in humans due to the loss of uricase activity by various mutations of its gene during the Miocene epoch. Loss of uricase activity led to humans having higher UA levels than other mammals. The high renal tubular reabsorption of UA and the previous loss of the ability to synthesise vitamin C may have also contributed to increased levels of UA in humans. The biological reason for the loss of uricase activity and increased levels of UA in humans and certain primates is unknown. UA is one of the most important antioxidants in human biological fluids. UA probably has neuroprotective activity. The current large increase in UA levels in humans in developed countries is mainly influenced by eating habits and lifestyle changes. Hyperuricaemia can cause gout and uric lithiasis, and is associated with hypertension, metabolic syndrome, renal disease and cardiovascular disease.