Prions, proteins that can convert between structurally and functionally distinct states and serve as non-Mendelian mechanisms of inheritance, were initially discovered and only known in eukaryotes, and consequently considered to likely be a relatively late evolutionary acquisition. However, the recent discovery of prions in bacteria and viruses has intimated a potentially more ancient evolutionary origin. Here we provide evidence that prion-forming domains exist in the domain archaea, the last domain of life left unexplored with regard to prions. We searched for archaeal candidate prion-forming protein sequences computationally, described their taxonomic distribution and phylogeny, and analyzed their associated functional annotations. Using biophysical in vitro assays, cell-based and microscopic approaches, and dye-binding analyses, we tested select candidate prion-forming domains for prionogenic characteristics. Out of the 16 tested, 8 formed amyloids, and 6 acted as protein-based elements of information transfer driving non-Mendelian patterns of inheritance. We also identified short peptides from our archaeal prion candidates that can form amyloid fibrils independently. Lastly, candidates that tested positively in our assays had significantly higher tyrosine and phenylalanine content than candidates that tested negatively, an observation that may help future archaeal prion predictions. Taken together, our discovery of functional prion-forming domains in archaea provides evidence that multiple archaeal proteins are capable of acting as prions—thus expanding our knowledge of this epigenetic phenomenon to the third and final domain of life and bolstering the possibility that they were present at the time of the last universal common ancestor (LUCA).

中文翻译：

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寻找古代朊病毒：古细菌朊病毒样结构域形成基于淀粉样蛋白的表观遗传元件

朊病毒是一种可以在结构和功能不同状态之间转换并作为非孟德尔遗传机制的蛋白质，最初是在真核生物中发现的，并且只在真核生物中发现，因此被认为可能是相对较晚的进化获得。然而，最近在细菌和病毒中发现的朊病毒暗示了一个可能更古老的进化起源。在这里，我们提供的证据表明，在域古细菌中存在朊病毒形成域，这是关于朊病毒尚未探索的最后一个生命域。我们通过计算搜索了古细菌候选朊病毒形成蛋白序列，描述了它们的分类分布和系统发育，并分析了它们相关的功能注释。使用生物物理体外测定、基于细胞和显微方法以及染料结合分析，我们测试了选择的候选朊病毒形成域的朊病毒特性。在 16 种测试中，8 种形成淀粉样蛋白，6 种充当基于蛋白质的信息传递元素，驱动非孟德尔遗传模式。我们还从我们的古细菌朊病毒候选物中鉴定出可以独立形成淀粉样蛋白原纤维的短肽。最后，在我们的检测中检测呈阳性的候选者的酪氨酸和苯丙氨酸含量明显高于检测呈阴性的候选者，这一观察结果可能有助于未来的古细菌朊病毒预测。综合起来，