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. 2018 Dec;86(9):613-617. doi: 10.1007/s00239-018-9873-5. Epub 2018 Nov 3.

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.

Publication types

  • Letter
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Carrier Proteins
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / metabolism
  • Gene Expression Regulation / genetics
  • Genetic Predisposition to Disease / genetics
  • Guinea Pigs / genetics*
  • Humans
  • Insulin / genetics
  • Insulin / metabolism
  • Insulin Secretion / genetics
  • Mice
  • Pseudogenes / genetics
  • Sequence Homology, Amino Acid
  • Zinc / metabolism
  • Zinc Transporter 8 / genetics*
  • Zinc Transporter 8 / metabolism*

Substances

  • Carrier Proteins
  • Insulin
  • SLC30A8 protein, human
  • Zinc Transporter 8
  • zinc-binding protein
  • Zinc