Dr. Kumar’s Take
This study used a fascinating approach called ancestral sequence reconstruction to “resurrect” ancient versions of uricase, the enzyme that breaks down uric acid. What they found was that uricase did not suddenly disappear in humans and apes. Instead, it weakened step by step across millions of years before finally being shut down. This gradual loss likely helped our ancestors survive by storing more fat from fruit sugar (fructose) during times of food shortage. But today, that same genetic change contributes to high uric acid levels, gout, obesity, and metabolic disease.
Key Takeaways
✔ Humans and apes lost uricase gradually through small genetic changes before final gene shutdown.
✔ Rising uric acid helped ancient primates store fat, a survival advantage during food scarcity.
✔ High uric acid now raises risk for gout, kidney disease, and metabolic syndrome.
✔ Resurrected ancient uricase shows potential as a therapy for modern patients with gout.
Actionable Tip
Ask your doctor about checking your uric acid levels, even if you have never had gout. Keeping uric acid under 6.0 mg/dL helps lower long-term risks for heart, kidney, and metabolic problems.
Brief Summary
Published in PNAS (2014), this study recreated ancient uricase enzymes from mammalian ancestors. Researchers showed that uricase activity steadily declined over time, long before the gene was completely disabled in apes about 15–20 million years ago. Experiments in human liver cells confirmed that ancient uricase could protect against fat buildup from fructose. The study suggests uricase loss may have been an evolutionary “thrifty gene” that helped apes survive changing environments but now contributes to modern health challenges.
Study Design
- Approach: Ancestral sequence reconstruction and protein resurrection.
- Comparisons: Ancient and modern uricases from mammals, including structural biology and enzymatic assays.
- Tests:
- Resurrected ancient uricases introduced into human liver cells.
- Fructose metabolism tracked with and without uricase.
- Pharmacokinetics of an ancient uricase tested in rodents.
Results
- Progressive decline: Uricase efficiency decreased step by step over millions of years.
- Fructose-fat link: Ancient uricase reduced fat buildup in liver cells exposed to fructose.
- Therapeutic potential: One ancestral uricase was more efficient and more stable than modern therapeutic uricases, suggesting possible use in gout treatment.
- Evolutionary insight: The gradual decline in uricase may have helped apes adapt to environments with less food, favoring fat storage as an energy reserve.
Why the Loss of Uricase Matters
Uric acid is both protective and harmful. At moderate levels, it may defend against oxidative stress and support survival. But at high levels, it crystallizes in joints and kidneys, leading to gout, stones, and heart risk. This study explains why humans walk such a delicate balance with uric acid, a balance written into our evolutionary history.
Related Studies and Research
Loss of Uricase in Human Evolution and Health – Examines the loss of uricase across primate evolution and its modern effects.
Glorification of Gout in Literature – Looks at the social framing of gout through history.
Vitamin C and Uric Acid: Gout Study – Investigates vitamin C’s impact on uric acid and gout risk.
Podcast: How to Make Gout Disappear from Your Life – A comprehensive look at modern and ancient gout science—and how to beat it.
Frequently Asked Questions
Why did humans lose uricase?
Small genetic changes slowly reduced uricase efficiency until the gene shut down. This likely gave survival advantages by boosting fat storage in times of scarcity.
Does uric acid have benefits?
Yes. It may act as an antioxidant and protect the brain. But too much uric acid increases disease risk.
Can uricase be used as a treatment?
Yes. Modified uricase therapies (like pegloticase) already exist for severe gout. Ancient uricases studied here may offer new, more stable options.
What foods raise uric acid?
Fructose (from sugary drinks and processed foods), alcohol, and purine-rich foods like organ meats and some seafood.
Conclusion
The story of uricase is a reminder of how evolution shaped our biology for survival in ancient times but left us vulnerable today. By understanding why humans lost uricase, we gain insight into gout, obesity, and metabolic disease. More importantly, this research shows that looking backward, even resurrecting ancient proteins, can help us design better treatments for modern health problems.