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Non-unity molecular heritability demonstrated by continuous evolution in vitroINTRODUCTION: When catalytic RNA is evolved in vitro, the molecule's chemical reactivity is usually the desired selection target. Sometimes the phenotype of a particular RNA molecule cannot be unambiguously determined from its genotype, however. This can occur if a nucleotide sequence can adopt multiple folded states, an example of non-unity heritability (i.e. one genotype gives rise to more than one phenotype). In these cases, more rounds of selection are required to achieve a phenotypic shift. We tested the influence of non-unity heritability at the molecular level by selecting for variants of a ligase ribozyme via continuous evolution. RESULTS: During 20 bursts of continuous evolution of a 152-nucleotide ligase ribozyme in which the Mg2+ concentration was periodically lowered, a nine-error variant of the starting 'wild-type' molecule became dominant in the last eight bursts. This variant appears to be more active than the wild type. Kinetic analyses of the mutant suggest that it may not possess a higher first-order catalytic rate constant, however. Examination of the multiple RNA conformations present under the continuous evolution conditions suggests that the mutant is superior to the wild type because it is less likely to misfold into inactive conformers. CONCLUSIONS: The evolution of genotypes that are more likely to exhibit a particular phenotype is an epiphenomenon usually ascribed only to complex living systems. We show that this can occur at the molecular level, demonstrating that in vitro systems may have more life-like characteristics than previously thought, and providing additional support for an RNA world.
Document ID
20040141708
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Schmitt, T.
(University at Albany NY 12222, United States)
Lehman, N.
Date Acquired
August 22, 2013
Publication Date
December 1, 1999
Publication Information
Publication: Chemistry & biology
Volume: 6
Issue: 12
ISSN: 1074-5521
Subject Category
Exobiology
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Discipline Exobiology

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