Scarcity of fruit millions of years ago could have caused loss of enzyme that prevents gout

February 18, 2014 by Marcia Malory, Medical Xpress report
Gout in X-ray of left foot. Credit: Hellerhoff/Wikipedia.

(Medical Xpress)—Apes, including humans, lack an enzyme called uricase that breaks down uric acid. Because we lack uricase, we are predisposed to developing gout. After reconstructing ancient versions of the enzyme found in other mammals, Eric Gaucher of the Georgia Institute of Technology and his colleagues have concluded that apes lost the ability to produce uricase so they could better convert fructose, fruit sugar, to fat for survival when fruit was scarce. The research appears in the Proceedings of the National Academy of Sciences.

Gout is a painful condition caused by crystals building up in the joints. It occurs when there is so much uric acid in the blood the kidneys can't process it all. Most have an enzyme called uricase that breaks down uric acid into substances that are easier to excrete. In apes, however, a mutation makes the gene that produces uricase ineffective. Consequently, apes have three to ten times more uric acid in their blood than other mammals.

Gaucher and his team wanted to understand how the ability to produce uricase changed over the course of . They reconstructed ancient versions of the enzyme, starting with that produced by the last common ancestor of mammals about 90 million years ago. The researchers found that over time, mutations in the gene that codes for uricase made the progressively less effective. Finally, about 17 million years ago, apes developed a mutation that causes us not to produce any uricase at all.

The team noticed that the greatest reduction in uricase's effectiveness took place when the Earth was cooling. From this, they hypothesized a connection between the decreasing ability to metabolize uric acid and an increasing scarcity of fruit. Uric acid is a byproduct of the breakdown of fructose and stimulates us to create fat stores. As the climate cooled and fruit became harder to find in winter, high levels of uric acid would have made it easier to store fat and therefore made survival more likely. To test their hypothesis, the researchers added ancient versions of uricase to human cells and then examined how these cells responded to fructose. They discovered that the cells produced less fat.

Gaucher's team think their discovery could provide support for the "thrifty gene" hypothesis, which says that the propensity for modern-day humans to become obese comes from our ancestors' need to store fat efficiently to prepare for times of scarcity. Previous research shows an association between high levels of uric acid and metabolic syndrome, a condition associated with obesity. The team believes reengineering ancient forms of uricase for use in humans would have therapeutic benefits.

Explore further: Adding uric acid to standard stroke clot busters reduces stroke disability

More information: "Evolutionary history and metabolic insights of ancient mammalian uricases," by James T. Kratzer et al. PNAS,

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Feb 18, 2014
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1 / 5 (4) Feb 18, 2014
The link from ambient temperature (cooling) consistently shows what causes de novo creation of genes and chromosomal rearrangements in species from yeasts to human. The change in the enzyme is clearly nutrient-dependent and pheromone-controlled. It is not biologically plausible for it to be due to an accumulation of mutations. It is an epigenetically-effected change that exemplifies ecological adaptations, which occur in all species.

If any species had to wait for accumulated mutations associated with temperature changes to cause them to evolve into another species, there would be no such thing as evolution. What does that tell you about what you were taught to believe?

Instead, conserved molecular mechanisms in species from microbes to man assure us that what happens in flies is not an ecological outlier, and it doesn't happen due to mutations.


Genome-wide evolutionary response to a heat wave in Drosophila
1 / 5 (2) Feb 18, 2014

Actually what you are saying makes a lot of sense given what we know today about the epigenome. I will read the link to see how pheremones play a role.
5 / 5 (5) Feb 19, 2014
Some pretty obnoxious statements that are unscientific.
"apes, including humans..."

No. Humans are not apes. Strange wording.

"apes lost the ability to produce uricase..."

No. There is no evidence for that. No evidence that apes ever had that ability.

"they hypothesized a connection between the decreasing ability to metabolize uric acid and an increasing scarcity of fruit...."

Crazy. Just a wild supposition.

physorg, please stick to real science.

Nope you are wrong. Read further..not a speculation, they tested it. That's what scientists do.
No evidence, how about fossil remnants of those ancient genes?
Humans DO belong in that group. Geesh...stop talking nonsense.
1 / 5 (3) Feb 19, 2014
They provide experimental evidence that clearly shows HOW ecological adaptations occur in species from microbes to man. This published work is an unparalleled refutation of mutation-initiated natural selection.

The refutation is unparalleled because mutation-driven evolution was such a straightforward hypothesis that no experimental test of what became the "cornerstone" of neo-Darwinism was ever attempted until last year. That's when researchers reported that mutations were not fixed in the DNA of the organzed genome of C. elegans.

These results show that mutations are not fixed in the DNA of the organized genome of primates, which extends my model of nutrient-dependent pheromone-controlled ecological adaptations from microbes to man.

5 / 5 (2) Feb 19, 2014
@Verkle, This is why I dislike biological terminology, the common names for the latin categories are really confusing. In biology, the word Ape is used for the superfamily "Hominoidae", which includes what we colloquially refer to as apes and also humans. So it is technically correct to say humans belong to the family of apes. But I do think it's very important to use an easy to understand language, so as to not breed ignorance and ill-sentiment towards science, which is often the case when humans are referred to as apes. A more descriptive translation of Hominoidae would be "human-like primate", which I think would not instill as much confusion.
1 / 5 (1) Feb 21, 2014
The totally absurd posts above notwithstanding, these scientists do appear to have missed the mark. In reality, we lost uricase at the same time that we lost the ability to manufacture vitamin C endogenously. Uric acid is an antioxidant that, in part, took its place.
1 / 5 (3) Feb 21, 2014
In reality, we lost uricase at the same time that we lost the ability to manufacture vitamin C endogenously. Uric acid is an antioxidant that, in part, took its place.

Thanks. Do you know anything about the molecular mechanisms by which uric acid stabilizes hydrogen bonds in RNA or DNA, and what might have precipitated the change from base pair stabilization by Vitamin C to stabilization by uric acid, but only in the presence of enough Vitamin C to enable the ecological adaptation?

I may not know enough to ask the question, and apologize if it is too ignorant to answer.

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