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Robust Yet Fragile: Expression Noise, Protein Misfolding, and Gene Dosage in the Evolution of Genomes

Robust Yet Fragile: Expression Noise, Protein Misfolding, and Gene Dosage in the Evolution of... The complex manner in which organisms respond to changes in their gene dosage has long fascinated geneticists. Oddly, although the existence of dominance implies that dosage reductions often have mild phenotypes, extra copies of whole chromosomes (aneuploidy) are generally strongly deleterious. Even more paradoxically, an extra copy of the genome is better tolerated than is aneuploidy. We review the resolution of this paradox, highlighting the roles of biochemistry, protein aggregation, and disruption of cellular microstructure in that explanation. Returning to life's curious combination of robustness and sensitivity to dosage changes, we argue that understanding how biological robustness evolved makes these observations less inexplicable. We propose that noise in gene expression and evolutionary strategies for its suppression play a role in generating dosage phenotypes. Finally, we outline an unappreciated mechanism for the preservation of duplicate genes, namely preservation to limit expression noise, arguing that it is particularly relevant in polyploid organisms. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annual Review of Genetics Annual Reviews

Robust Yet Fragile: Expression Noise, Protein Misfolding, and Gene Dosage in the Evolution of Genomes

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References (140)

Publisher
Annual Reviews
Copyright
Copyright © 2016 by Annual Reviews. All rights reserved
ISSN
0066-4197
eISSN
1545-2948
DOI
10.1146/annurev-genet-120215-035400
pmid
27617972
Publisher site
See Article on Publisher Site

Abstract

The complex manner in which organisms respond to changes in their gene dosage has long fascinated geneticists. Oddly, although the existence of dominance implies that dosage reductions often have mild phenotypes, extra copies of whole chromosomes (aneuploidy) are generally strongly deleterious. Even more paradoxically, an extra copy of the genome is better tolerated than is aneuploidy. We review the resolution of this paradox, highlighting the roles of biochemistry, protein aggregation, and disruption of cellular microstructure in that explanation. Returning to life's curious combination of robustness and sensitivity to dosage changes, we argue that understanding how biological robustness evolved makes these observations less inexplicable. We propose that noise in gene expression and evolutionary strategies for its suppression play a role in generating dosage phenotypes. Finally, we outline an unappreciated mechanism for the preservation of duplicate genes, namely preservation to limit expression noise, arguing that it is particularly relevant in polyploid organisms.

Journal

Annual Review of GeneticsAnnual Reviews

Published: Nov 23, 2016

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