SLC52A1 is a neofunctionalized primate urate transporter enabling intestinal urate secretion

Area of Science:

• Evolutionary biology
• Biochemistry
• Genetics

Background:

• Hominoids exhibit elevated serum urate levels due to the evolutionary absence of the uricase enzyme.
• The precise mechanism driving the loss of uricase during primate evolution remains incompletely understood.

Purpose of the Study:

• To investigate the role of the neofunctionalized SLC52A1 gene in the evolutionary loss of uricase.
• To elucidate the urate transport mechanisms involving SLC52A1 in primates.

Main Methods:

• Synteny analysis to trace gene duplication events.
• Functional studies of primate SLC52A1, including urate and riboflavin transport assays.
• Cellular uptake and efflux studies using human SLC52A1.
• Transcellular transport studies in enterocytes to examine SLC52A1 localization and function.

Main Results:

• SLC52A1, duplicated from the conserved SLC52A2 gene, was found to transport both urate and riboflavin in primates.
• Human SLC52A1 facilitates the cellular uptake and efflux of urate via facilitated diffusion.
• Basolaterally localized SLC52A1 in enterocytes collaborates with luminally localized ABCG2 to promote urate removal.

Conclusions:

• The emergence of SLC52A1-mediated intestinal urate transport likely preceded and facilitated the evolutionary loss of uricase in hominoids.
• This novel transport system provided an adaptive advantage, allowing for increased serum urate levels without the ancestral uricase enzyme.