ArticleMolecular biology and evolution2022
Phylogenetic Articulation of Uric Acid Evolution in Mammals and How It Informs a Therapeutic Uricase.
Article in Molecular biology and evolution, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 32 citations in OpenAlex.
- SLC52A1 is a neofunctionalized primate urate transporter enabling intestinal urate secretion.The Journal of biological chemistry · 2026Article
- Article
- Uric Acid Monohydrate Nanocrystals: An Adaptable Platform for Nitrogen and Salt Management in Reptiles.Journal of the American Chemical Society · 2025Article
- Genomic insertion of ancestral uricase into human liver cells to determine metabolic consequences of pseudogenization.Scientific reports · 2025Article
- The Role of Purine Metabolism and Uric Acid in Postnatal Neurologic Development.Molecules (Basel, Switzerland) · 2025Review
- Molecular Pharmacology of Vitamin C and Relevance to Health and Obesity-A Narrative Review.International journal of molecular sciences · 2024Review
- Recombinant Expression and Functional Assessment of Uricase from a Pertinent Origin of the Enzyme,Iranian journal of biotechnology · 2024Article
- Mechanisms and rationale for uricase use in patients with gout.Nature reviews. Rheumatology · 2023Review
- The Role of Uric Acid in Human Health: Insights from theJournal of personalized medicine · 2023Review
- Cysteine Enrichment Mediates Co-Option of Uricase in Reptilian Skin and Transition to Uricotelism.Molecular biology and evolution · 2023Article
- Oral Delivery of Nanoparticles Carrying Ancestral Uricase Enzyme Protects against Hyperuricemia in Knockout Mice.Biomacromolecules · 2023Article
- Do thrifty genes exist? Revisiting uricase.Obesity (Silver Spring, Md.) · 2022Review
- Diverse functions associate with non-coding polymorphisms shared between humans and chimpanzees.BMC ecology and evolution · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The role of uric acid during primate evolution has remained elusive ever since it was discovered over 100 years ago that humans have unusually high levels of the small molecule in our serum. It has been difficult to generate a neutral or adaptive explanation in part because the uricase enzyme evolved to become a pseudogene in apes thus masking typical signals of sequence evolution. Adding to the difficulty is a lack of clarity on the functional role of uric acid in apes. One popular hypothesis proposes that uric acid is a potent antioxidant that increased in concentration to compensate for the lack of vitamin C synthesis in primate species ∼65 Ma. Here, we have expanded on our previous work with resurrected ancient uricase proteins to better resolve the reshaping of uricase enzymatic activity prior to ape evolution. Our results suggest that the pivotal death-knell to uricase activity occurred between 20 and 30 Ma despite small sequential modifications to its catalytic efficiency for the tens of millions of years since primates lost their ability to synthesize vitamin C, and thus the two appear uncorrelated. We also use this opportunity to demonstrate how molecular evolution can contribute to biomedicine by presenting ancient uricases to human immune cells that assay for innate reactivity against foreign antigens. A highly stable and highly catalytic ancient uricase is shown to elicit a lower immune response in more human haplotypes than other uricases currently in therapeutic development.
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