Chakrabortee Sohini, Byers James S, Jones Sandra, Garcia David M, Bhullar Bhupinder, Chang Amelia, She Richard, Lee Laura, Fremin Brayon, Lindquist Susan, Jarosz Daniel F
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
Cell. 2016 Oct 6;167(2):369-381.e12. doi: 10.1016/j.cell.2016.09.017. Epub 2016 Sep 29.
Prions are a paradigm-shifting mechanism of inheritance in which phenotypes are encoded by self-templating protein conformations rather than nucleic acids. Here, we examine the breadth of protein-based inheritance across the yeast proteome by assessing the ability of nearly every open reading frame (ORF; ∼5,300 ORFs) to induce heritable traits. Transient overexpression of nearly 50 proteins created traits that remained heritable long after their expression returned to normal. These traits were beneficial, had prion-like patterns of inheritance, were common in wild yeasts, and could be transmitted to naive cells with protein alone. Most inducing proteins were not known prions and did not form amyloid. Instead, they are highly enriched in nucleic acid binding proteins with large intrinsically disordered domains that have been widely conserved across evolution. Thus, our data establish a common type of protein-based inheritance through which intrinsically disordered proteins can drive the emergence of new traits and adaptive opportunities.
朊病毒是一种具有范式转变意义的遗传机制，其中表型由自我模板化的蛋白质构象而非核酸编码。在此，我们通过评估几乎每个开放阅读框（ORF；约5300个ORF）诱导可遗传性状的能力，来研究酵母蛋白质组中基于蛋白质的遗传范围。近50种蛋白质的瞬时过表达产生了一些性状，这些性状在其表达恢复正常后很长时间仍可遗传。这些性状是有益的，具有类似朊病毒的遗传模式，在野生酵母中很常见，并且仅通过蛋白质就能传递给未接触过的细胞。大多数诱导蛋白不是已知的朊病毒，也不形成淀粉样蛋白。相反，它们在具有广泛保守的大的内在无序结构域的核酸结合蛋白中高度富集。因此，我们的数据建立了一种基于蛋白质的常见遗传类型，通过这种类型，内在无序的蛋白质可以推动新性状和适应性机会的出现。
