Evolutionary history and metabolic insights of ancient mammalian uricases

• DOI: 10.1073/pnas.1320393111
• Publication Date: 2014-02-19T01:52:24Z
• Authors: James T. Kratzer; Miguel A. Lanaspa; Michael N. Murphy; Christina Cicerchi; Christina L. Graves; Peter A. Tipton; Eric A. Ortlund; Richard J. Johnson; Eric A. Gaucher
• Keywords: Models, Molecular; Models, Genetic; Urate Oxidase; Protein Conformation; Adaptation, Biological; Computational Biology; Bayes Theorem; Hominidae; Hep G2 Cells; Models, Biological; Rats; Evolution, Molecular; Rats, Sprague-Dawley; Adipose Tissue; Fruit; Animals; Humans; Phylogeny; Pseudogenes; DNA Primers

Significance Human susceptibility to gout is driven by the fact that we have a pseudogene for uricase that prevents a functional enzyme from being produced. Our inability to convert highly insoluble uric acid into a more soluble molecule makes us vulnerable to disease and other health complications. We have exploited ancestral sequence reconstruction to better understand how and why apes lost this functional enzyme. Our ancient proteins support one hypothesis that the progressive loss of uricase activity allowed our ancestors to readily accumulate fat via the metabolism of fructose from fruits. This adaptation may have provided our ancestors with an advantage when the energy-rich rainforests of Europe and Asia were displaced by temperate forests by the end of the Oligocene.