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dc.contributor.authorBartel, David
dc.contributor.authorCurtis, Edward A.
dc.date.accessioned2015-03-27T16:14:25Z
dc.date.available2015-03-27T16:14:25Z
dc.date.issued2013-06
dc.date.submitted2012-12
dc.identifier.issn1355-8382
dc.identifier.issn1469-9001
dc.identifier.urihttp://hdl.handle.net/1721.1/96216
dc.description.abstractThe relationship between genotype and phenotype is often described as an adaptive fitness landscape. In this study, we used a combination of recombination, in vitro selection, and comparative sequence analysis to characterize the fitness landscape of a previously isolated kinase ribozyme. Point mutations present in improved variants of this ribozyme were recombined in vitro in more than 10[superscript 14] different arrangements using synthetic shuffling, and active variants were isolated by in vitro selection. Mutual information analysis of 65 recombinant ribozymes isolated in the selection revealed a rugged fitness landscape in which approximately one-third of the 91 pairs of positions analyzed showed evidence of correlation. Pairs of correlated positions overlapped to form densely connected networks, and groups of maximally connected nucleotides occurred significantly more often in these networks than they did in randomized control networks with the same number of links. The activity of the most efficient recombinant ribozyme isolated from the synthetically shuffled pool was 30-fold greater than that of any of the ribozymes used to build it, which indicates that synthetic shuffling can be a rich source of ribozyme variants with improved properties.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant GM061835)en_US
dc.language.isoen_US
dc.publisherCold Spring Harbor Laboratory Pressen_US
dc.relation.isversionofhttp://dx.doi.org/10.1261/rna.037572.112en_US
dc.rightsCreative Commons Attribution-NonCommercial 3.0 Unported Licenceen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/en_US
dc.sourceCold Spring Harbor Laboratory Pressen_US
dc.titleSynthetic shuffling and in vitro selection reveal the rugged adaptive fitness landscape of a kinase ribozymeen_US
dc.typeArticleen_US
dc.identifier.citationCurtis, E. A., and D. P. Bartel. “Synthetic Shuffling and in Vitro Selection Reveal the Rugged Adaptive Fitness Landscape of a Kinase Ribozyme.” RNA 19, no. 8 (June 24, 2013): 1116–1128.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.mitauthorBartel, Daviden_US
dc.relation.journalRNAen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsCurtis, E. A.; Bartel, D. P.en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-3872-2856
mit.licensePUBLISHER_CCen_US
mit.metadata.statusComplete


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