Uric acid: the past decade.

In the greater tree of life, the “rise” of uric acid in the circulation of living organisms is a relatively recent event (1). In the majority of species that generate uric acid as the end product of purine metabolism, urate is transformed into a more soluble allantoin by urate oxidase (“uricase”) (2). However, it is presently believed that some 10-20 million years ago 2 independent mutations in the uricase gene occurred and were kept in a very small subset of species (including the ancestors of apes and humans) – most likely by positive selection (3). Many elements of this story remain a mystery even to this date. Why did some primates lose uricase activity some 15 million years ago? What was the selective advantage of having 10-fold higher serum urate levels compared with other mammals? Was it related to the development of cognitive abilities? Did it serve as a protection against infectious agents of those times? Did it buffer the effects of oxidative stress and contribute to present-day longevity? Why do male humans have much higher serum levels than female? Is uric acid a friend or a foe – is it a protective factor or a risk factor, and against (or for) what? What levels should be considered too high? Or too low? What causes the variation in its levels within and between humans? All these fundamental questions remain unanswered to this day (4,5).