TY - JOUR
T1 - Epigenetic regulation of translation reveals hidden genetic variation to produce complex traits
AU - True, Heather L.
AU - Bedin, Ilana
AU - Lindquist, Susan L.
N1 - Funding Information:
Acknowledgements We thank D. Huang, Y. Li, Q. Pan, Q. Qi, S. Wang, Yanfen Wang, Yifeng Wang, Z. Yang and others for their contributions to the long-term data collection at IMGERS. This project was supported by the State Key Basic Research and Development Plan of China, the Natural Science Foundation of China and the Knowledge Innovation Program of the Chinese Academy of Sciences.
Funding Information:
Acknowledgements We thank members of the Lindquist lab, the True lab, R. Parker and J. Masel for discussions and comments on experiments and the manuscript. We thank J. Weissman, S. Liebman and their lab members for plasmids and strains. This research was supported by the National Institutes of Health.
PY - 2004/9/9
Y1 - 2004/9/9
N2 - Phenotypic plasticity and the exposure of hidden genetic variation both affect the survival and evolution of new traits, but their contributing molecular mechanisms are largely unknown. A single factor, the yeast prion [PSI+], may exert a profound effect on both. [PSI+] is a conserved, protein-based genetic element that is formed by a change in the conformation and function of the translation termination factor Sup 35p, and is transmitted from mother to progeny. Curing cells of [PSI+] alters their survival in different growth conditions and produces a spectrum of phenotypes in different genetic backgrounds. Here we show, by examining three plausible explanations for this phenotypic diversity, that all traits tested involved [PSI+]-mediated read-through of nonsense codons. Notably, the phenotypes analysed were genetically complex, and genetic re-assortment frequently converted [PSI+]-dependent phenotypes to stable traits that persisted in the absence of [PSI+]. Thus, [PSI+] provides a temporary survival advantage under diverse conditions, increasing the likelihood that new traits will become fixed by subsequent genetic change. As an epigenetic mechanism that globally affects the relationship between genotype and phenotype, [PSI+] expands the conceptual framework for phenotypic plasticity, provides a one-step mechanism for the acquisition of complex traits and affords a route to the genetic assimilation of initially transient epigenetic traits.
AB - Phenotypic plasticity and the exposure of hidden genetic variation both affect the survival and evolution of new traits, but their contributing molecular mechanisms are largely unknown. A single factor, the yeast prion [PSI+], may exert a profound effect on both. [PSI+] is a conserved, protein-based genetic element that is formed by a change in the conformation and function of the translation termination factor Sup 35p, and is transmitted from mother to progeny. Curing cells of [PSI+] alters their survival in different growth conditions and produces a spectrum of phenotypes in different genetic backgrounds. Here we show, by examining three plausible explanations for this phenotypic diversity, that all traits tested involved [PSI+]-mediated read-through of nonsense codons. Notably, the phenotypes analysed were genetically complex, and genetic re-assortment frequently converted [PSI+]-dependent phenotypes to stable traits that persisted in the absence of [PSI+]. Thus, [PSI+] provides a temporary survival advantage under diverse conditions, increasing the likelihood that new traits will become fixed by subsequent genetic change. As an epigenetic mechanism that globally affects the relationship between genotype and phenotype, [PSI+] expands the conceptual framework for phenotypic plasticity, provides a one-step mechanism for the acquisition of complex traits and affords a route to the genetic assimilation of initially transient epigenetic traits.
UR - http://www.scopus.com/inward/record.url?scp=4544235083&partnerID=8YFLogxK
U2 - 10.1038/nature02885
DO - 10.1038/nature02885
M3 - Article
C2 - 15311209
AN - SCOPUS:4544235083
SN - 0028-0836
VL - 431
SP - 184
EP - 187
JO - Nature
JF - Nature
IS - 7005
ER -