Fructose, uricase, and the Back‐to‐Africa hypothesis

Abstract In the Middle Miocene (approximately 17 to 12 Ma) at least two radiations of fossil apes from East Africa into Eurasia occurred, and, while controversial, some paleoanthropological studies suggest that one of the Eurasian lineages may have returned to Africa to evolve into humans and the African apes. Here, we present a novel argument supporting this hypothesis. Specifically, the global cooling that occurred in the middle Miocene rendered hominoids living in Europe at risk for starvation as seasonal climate change resulted in less availability of fruits during the winter months. During this time, a mutation in uricase occurred in early hominids that resulted in a rise in serum uric acid. Uric acid has been found to potentiate the effect of fructose to increase fat stores, suggesting that the mutation provided a survival advantage. Such a survival advantage would have been less likely to occur in Africa, where the continued presence of tropical rainforests would have been more likely to provide food throughout the year. Furthermore, Miocene apes in Europe were in protected sites where geographic isolation could have allowed the uricase mutation to be rapidly expressed in the entire population. While speculative, we suggest that the uricase mutation supports an extra‐Africa origin of humans.