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This is a story about how a human evolutionary advantage is now turning into a challenge in modern society.


  • The story starts with a very simple yet special molecule called uric acid (UA).

  • UA  is a common molecule in the bodies of all animals.

  • The molecule resembles caffeine.

  • It's a powerful antioxidant but also rather insoluble.

  • Across almost all kingdoms of life, most animals carefully regulate the concentration of UA in their blood using an enzyme called uricase

  • However, during hominid evolution, Great Apes progressively lost the ability to degrade UA over millions of years, starting ~17 millon years ago (Kratzer et al., 2014).

  • Great Apes cannot degrade UA

  • In fact, humans are now the species with the highest basal UA levels of any animal!

​ Why does this matter? 

  • On the one hand, we have more of this important antioxidant which increases human longevity. High levels of uric acid are regarded as an important human evolutionary advantage (ref). The loss of uricase also helped frugivores convert fruit sugars (fructose) into fats.

  • On the other hand, like all things, too much is not good.

  • As mentioned above UA is highly insoluble.

  • At too high a concentration in our blood, UA crystals precipitate in soft tissues.

  • This excess UA condition is called hyperuricemia, and it acutely causes liver and kidney damage or chronically causes gout (ref).

​ So what?

  • Human diets changed a lot in the last centuries and are still evolving.

  • Lets look at we ingest UA. 

  • Two main sources of UA are excessive fructose (ref) and DNA/RNA digestion.  

  • When our body breaks down some parts of DNA/RNA (called purines) in our foods, we end up stuck with UA formation because we lack the enzyme uricase to break this down further to the next step (the more soluble 5-hydroxyisourate).

  • This is usually not an issue in a regular diet, because the precursors of UA, that is, DNA and RNA, are not in high abundance.

  • But ironically, this evolutionary advantage is now posing a challenge for the microbial foods industry, because fast growing microbes have much more DNA/RNA than most life forms.

  • The European Food and Safety Authority regulation states that a safe level of consumption is no more than 4 g/day of DNA/RNA per person (ref).

  • Therefore the fermented protein industry is carefully designing “downstream processing” to remove DNA/RNA from microbial foods to make sure humans don’t eat too much of this product.

  • There are a number of techniques to achieve this, like heat treatment, filtrations and others. Connectomix is studying these processes carefully.

  • It's interesting to think how an evolutionary advantage in one period of time, or in one environment, can become a challenge in another.

Uricase activity declined in hominid evolution (Chang et al., 2014)

The Story of Uric Acid

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