Humans lack the enzyme uricase, and the enzyme that allows most other organisms to synthesize vitamin C, so we are vulnerable to gout and scurvy.  Why?  In this interesting article, dedicated to the memory of James Neel, the authors hypothesize that the mutations knocking out these enzymes were selected for because they increased our ancestor’s ability to store fructose as fat.  When these changes interact with modern 20 fold increases of fructose in the diet, obesity results.

The Evolution of Obesity: Insights from the Mid-Miocene

Johnson, RJ, P Andrews, SA Benner, and W Oliver

Transactions of the American Clinical and Climatological Association 121:295-308, 2010

Abstract

All humans are double knockouts. Humans lack the ability to synthesize vitamin C due to a mutation in L-gulono-lactone oxidase that occurred during the late Eocene, and humans have higher serum uric acid levels due to a mutation in uricase that occurred in the mid Miocene. In this paper we review the hypothesis that these mutations have in common the induction of oxidative stress that may have had prosurvival effects to enhance the effects of fructose to increase fat stores. Fructose was the primary nutrient in fruit which was the main staple of early primates, but this food likely became less available during the global cooling that occurred at the time of these mutations. However, in today’s society, the intake of fructose, primarily in the form of added sugars, has skyrocketed, while the intake of natural fruits high in vitamin C has fallen. We suggest that it is the interaction of these genetic changes with diet that is responsible for the obesity epidemic today. Hence, we propose that Neel’s thrifty gene hypothesis is supported by these new insights into the mechanisms regulating fructose metabolism.

Keywords: uricase, vitamin C, ascorbate, obesity, metabolic syndrome