Publication Date:
2016-04-16
Description:
Epistatic interactions play a fundamental role in molecular evolution, but little is known about the spatial distribution of these interactions within genes. To systematically survey a model landscape of intragenic epistasis, we quantified the fitness of ~60,000 Saccharomyces cerevisiae strains expressing randomly mutated variants of the 333-nucleotide-long U3 small nucleolar RNA (snoRNA). The fitness effects of individual mutations were correlated with evolutionary conservation and structural stability. Many mutations had small individual effects but had large effects in the context of additional mutations, which indicated negative epistasis. Clusters of negative interactions were explained by local thermodynamic threshold effects, whereas positive interactions were enriched among large-effect sites and between base-paired nucleotides. We conclude that high-throughput mapping of intragenic epistasis can identify key structural and functional features of macromolecules.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Puchta, Olga -- Cseke, Botond -- Czaja, Hubert -- Tollervey, David -- Sanguinetti, Guido -- Kudla, Grzegorz -- 077248/Wellcome Trust/United Kingdom -- 097383/Wellcome Trust/United Kingdom -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2016 May 13;352(6287):840-4. doi: 10.1126/science.aaf0965. Epub 2016 Apr 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, Scotland, UK. ; School of Informatics, University of Edinburgh, Edinburgh, Scotland, UK. ; Scott Tiger SA, Warsaw, Poland. ; SynthSys, Centre for Synthetic and Systems Biology, University of Edinburgh, Edinburgh, Scotland, UK. Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, Scotland, UK. ; School of Informatics, University of Edinburgh, Edinburgh, Scotland, UK. SynthSys, Centre for Synthetic and Systems Biology, University of Edinburgh, Edinburgh, Scotland, UK. ; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, Scotland, UK. gkudla@gmail.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27080103" target="_blank"〉PubMed〈/a〉
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
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Chemistry and Pharmacology
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Computer Science
,
Medicine
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Natural Sciences in General
,
Physics
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