Abstract
In most mammals pancreatic islet beta cells have very high zinc levels that promote the crystallization and storage of insulin. Guinea pigs are unusual amongst mammals in that their islets have very low zinc content. The selectionist theory of insulin evolution proposes that low environmental zinc led to the selection of a mutation in Guinea pig insulin that negated the requirement for zinc binding. In mice deletion of the Slc30a8 gene, that encodes the zinc transporter ZnT8, markedly reduces islet zinc content. We show here that SLC30A8 is a pseudogene in Guinea pigs. We hypothesize that inactivation of the SLC30A8 gene led to low islet zinc content that allowed for the evolution of insulin that no longer bound zinc.
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Abbreviations
- GSIS:
-
Glucose-stimulated insulin secretion
- T2D:
-
Type 2 diabetes
- SNP:
-
Single nucleotide polymorphism
- GWAS:
-
Genome-wide association studies
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Acknowledgements
This research was supported by the following grants: RO’B, DK92589; MS, DK60667. KES and KJB were supported by the Vanderbilt Molecular Endocrinology Training Program Grant 5T32 DK07563.
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KES, KJB, JKO all contributed to gene expression analyses and wrote parts of the manuscript. MS and RO’B designed experiments and wrote parts of the manuscript.
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The authors have no financial interests that would result in a conflict of interest with respect to this work.
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Syring, K.E., Bosma, K.J., Oeser, J.K. et al. The Diabetes Susceptibility Gene SLC30A8 that Encodes the Zinc Transporter ZnT8 is a Pseudogene in Guinea Pigs Potentially Contributing to Low Guinea Pig Islet Zinc Content. J Mol Evol 86, 613–617 (2018). https://doi.org/10.1007/s00239-018-9873-5
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DOI: https://doi.org/10.1007/s00239-018-9873-5