Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0830, USA.
Genetics. 2012 Feb;190(2):569-79. doi: 10.1534/genetics.111.136655. Epub 2011 Nov 17.
[PSI+] is a prion of Sup35p, an essential translation termination and mRNA turnover factor. The existence of lethal [PSI+] variants, the absence of [PSI+] in wild strains, the mRNA turnover function of the Sup35p prion domain, and the stress reaction to prion infection suggest that [PSI+] is a disease. Nonetheless, others have proposed that [PSI+] and other yeast prions benefit their hosts. We find that wild Saccharomyces cerevisiae strains are polymorphic for the sequence of the prion domain and particularly in the adjacent M domain. Here we establish that these variations within the species produce barriers to prion transmission. The barriers are partially asymmetric in some cases, and evidence for variant specificity in barriers is presented. We propose that, as the PrP 129M/V polymorphism protects people from Creutzfeldt-Jakob disease, the Sup35p polymorphisms were selected to protect yeast cells from prion infection. In one prion incompatibility group, the barrier is due to N109S in the Sup35 prion domain and several changes in the middle (M) domain, with either the single N109S mutation or the group of M changes (without the N109S) producing a barrier. In another, the barrier is due to a large deletion in the repeat domain. All are outside the region previously believed to determine transmission compatibility. [SWI+], a prion of the chromatin remodeling factor Swi1p, was also proposed to benefit its host. We find that none of 70 wild strains carry this prion, suggesting that it is not beneficial.
PSI+是 Sup35p 的朊病毒，是一种必需的翻译终止和 mRNA 周转因子。致死性 [PSI+] 变体的存在、野生菌株中 [PSI+] 的缺失、Sup35p 朊病毒结构域的 mRNA 周转功能以及对朊病毒感染的应激反应表明 [PSI+] 是一种疾病。然而，其他人提出 [PSI+] 和其他酵母朊病毒对其宿主有益。我们发现野生酿酒酵母菌株在朊病毒结构域的序列上存在多态性，特别是在相邻的 M 结构域。在这里，我们确定了这些种内变异会产生朊病毒传播的障碍。在某些情况下，这些障碍存在部分不对称性，并提出了障碍中存在变体特异性的证据。我们提出，由于 PrP 129M/V 多态性保护人们免受克雅氏病的侵害，Sup35p 多态性被选择来保护酵母细胞免受朊病毒感染。在一个朊病毒不兼容组中，该障碍是由于 Sup35 朊病毒结构域中的 N109S 和中间 (M) 结构域中的几个变化引起的，只有单个 N109S 突变或 M 结构域的一组变化（不包括 N109S）会产生障碍。在另一个组中，该障碍是由于重复结构域中的一个大缺失引起的。所有这些都在以前被认为决定传播兼容性的区域之外。SWI+是染色质重塑因子 Swi1p 的朊病毒，也被提议对其宿主有益。我们发现，在 70 个野生菌株中没有一个携带这种朊病毒，这表明它没有益处。
