Uric acid: a danger signal from the RNA world that may have a role in the epidemic of obesity, metabolic syndrome, and cardiorenal disease: evolutionary considerations

Semin Nephrol. 2011 Sep;31(5):394-9. doi: 10.1016/j.semnephrol.2011.08.002.


All human beings are uricase knockouts; we lost the uricase gene as a result of a mutation that occurred in the mid-Miocene epoch approximately 15 million years ago. The consequence of being a uricase knockout is that we have higher serum uric acid levels that are less regulatable and can be readily influenced by diet. This increases our risk for gout and kidney stones, but there is also increasing evidence that uric acid increases our risk for hypertension, kidney disease, obesity, and diabetes. This raises the question of why this mutation occurred. In this article we review current hypotheses. We suggest that uric acid is a danger and survival signal carried over from the RNA world. The mutation of uricase that occurred during the food shortage and global cooling that occurred in the Miocene epoch resulted in a survival advantage for early primates, particularly in Europe. Today, the loss of uricase functions as a thrifty gene, increasing our risk for obesity and cardiorenal disease.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biological Evolution
  • Cardio-Renal Syndrome / epidemiology*
  • Cardio-Renal Syndrome / genetics*
  • Humans
  • Metabolic Syndrome / epidemiology*
  • Metabolic Syndrome / genetics*
  • Mutation
  • Obesity / epidemiology*
  • Obesity / genetics*
  • RNA*
  • Urate Oxidase / genetics
  • Uric Acid*


  • Uric Acid
  • RNA
  • Urate Oxidase