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Cell. 2016 Oct 6;167(2):369-381.e12. doi: 10.1016/j.cell.2016.09.017. Epub 2016 Sep 29.

Intrinsically Disordered Proteins Drive Emergence and Inheritance of Biological Traits.

Author information

1
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
2
Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
3
Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.
4
Department of Biology, Stanford University, Stanford, CA 94305, USA.
5
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; HHMI and Department of Biology, MIT, Cambridge, MA 02139, USA. Electronic address: lindquist_admin@wi.mit.edu.
6
Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA; Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA. Electronic address: jarosz@stanford.edu.

Abstract

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.

KEYWORDS:

epigenetics; intrinsic disorder; prions; protein folding

PMID:
27693355
PMCID:
PMC5066306
DOI:
10.1016/j.cell.2016.09.017
[Indexed for MEDLINE]
Free PMC Article

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