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Evidence that Evolution of the Diabetes Susceptibility Gene SLC30A8 that Encodes the Zinc Transporter ZnT8 Drives Variations in Pancreatic Islet Zinc Content in Multiple Species.
Journal of Molecular Evolution ( IF 2.1 ) Pub Date : 2019-07-04 , DOI: 10.1007/s00239-019-09898-0
Karin J Bosma 1 , Kristen E Syring 1 , James K Oeser 1 , Jason D Lee 1 , Richard K P Benninger 2 , Matthew E Pamenter 3, 4 , Richard M O'Brien 1
Affiliation  

Pancreatic islet zinc levels vary widely between species. Very low islet zinc levels in Guinea pigs were thought to be driven by evolution of the INS gene that resulted in the generation of an isoform lacking a histidine at amino acid 10 in the B chain of insulin that is unable to bind zinc. However, we recently showed that the SLC30A8 gene, that encodes the zinc transporter ZnT8, is a pseudogene in Guinea pigs, providing an alternate mechanism to potentially explain the low zinc levels. We show here that the SLC30A8 gene is also inactivated in sheep, cows, chinchillas and naked mole rats but in all four species a histidine is retained at amino acid 10 in the B chain of insulin. Zinc levels are known to be very low in sheep and cow islets. These data suggest that evolution of SLC30A8 rather than INS drives variation in pancreatic islet zinc content in multiple species.

中文翻译:

编码锌转运蛋白 ZnT8 的糖尿病易感基因 SLC30A8 的进化驱动多个物种胰岛锌含量变化的证据。

不同物种的胰岛锌水平差异很大。豚鼠体内极低的胰岛锌水平被认为是由 INS 基因的进化驱动的,该基因的进化导致胰岛素 B 链第 10 位氨基酸处缺乏组氨酸的亚型的产生,该亚型无法结合锌。然而,我们最近表明,编码锌转运蛋白 ZnT8 的 SLC30A8 基因是豚鼠的假基因,提供了一种可能解释低锌水平的替代机制。我们在此表明​​,SLC30A8 基因在绵羊、牛、栗鼠和裸鼹鼠中也失活,但在所有四种物种中,组氨酸都保留在胰岛素 B 链的第 10 位氨基酸处。众所周知,羊和牛胰岛中的锌含量非常低。
更新日期:2019-11-01
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