Ancient insights into uric acid metabolism in primates

Abstract

Why are humans susceptible to certain illnesses but not others? Diseases such as gout and hypertension have plagued us for centuries. The prevalence of gout in the United States has risen to 3.9% in recent years (1), and a staggering one in three adults have hypertension (2). It has often been assumed that some of the less than desirable aspects of our physiology are relics of our evolutionary past, but rarely have these ideas been subjected to experimental investigation, and many of these theories have been surprisingly difficult to prove (3). Although the idea of resurrecting ancient proteins using sequence information from extant organisms was first proposed half a century ago by Pauling and Zuckerkandl (4), it is only in the last decade or so that advances in phylogenetic likelihood and Bayesian models (5), combined with fast, inexpensive gene synthesis technology, have made this approach increasingly feasible. These methods have since been used with great success to investigate a variety of topics, including the evolution of protein regulatory complexes in developmental pathways (6), vertebrate steroid hormone receptors (7), paleoenvironments and the thermophilicity of early life (8), archosaur vision (9), vaccine development (10), yeast transcriptional circuits following gene duplication (11), and the evolution of complexity in coral fluorescent proteins (12). Evolutionary questions can be notoriously intractable to experimental investigation, but the recreation of ancestral proteins provides us a window to the past through which we can directly test hypotheses regarding our evolutionary history.