Intrinsically Disordered Proteins Drive Emergence and Inheritance of Biological Traits.
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.
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Sohini
S
Chakrabortee
Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
James S
JS
Byers
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Sandra
S
Jones
Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.
David M
DM
Garcia
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Bhupinder
B
Bhullar
Department of Biology, Stanford University, Stanford, CA 94305, USA.
Amelia
A
Chang
Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.
Richard
R
She
Department of Biology, Stanford University, Stanford, CA 94305, USA.
Laura
L
Lee
Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.
Brayon
B
Fremin
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.
Susan
S
Lindquist
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.
Daniel F
DF
Jarosz
D000682:Amyloid / Q000378:metabolism; D019143:Evolution, Molecular; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D064267:Intrinsically Disordered Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016366:Open Reading Frames; D011328:Prions / Q000737:chemistry / Q000378:metabolism; D020543:Proteome; D019655:Quantitative Trait, Heritable; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D000682:Amyloid; D018840:HSP70 Heat-Shock Proteins; C074510:HSP82 protein, S cerevisiae; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D064267:Intrinsically Disordered Proteins; D011328:Prions; D020543:Proteome; D029701:Saccharomyces cerevisiae Proteins; C070972:HsP104 protein, S cerevisiae
epigenetics; intrinsic disorder; prions; protein folding
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