Abstract
Experiments are described which demonstrate that it is possible to isolate in vitro a variety of mutant RNA molecules which exhibit qualitatively distinguishable phenotypes. The results suggest that precellular evolution could have involved selective forces of previously unsuspected diversity and subtlety.
Suitable adjustment of the selective conditions leads to the isolation of variants optimally designed to compete successfully with the original viral nucleic acid. One of the properties that can be built into the variants is resistance to the presence of inhibitory analogues of the normal riboside triphosphates. Potentially, such variants could be used as antiviral devices in conjunction with the more usual chemotherapeutic agents.
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- Bishop D. H., Claybrook J. R., Spiegelman S. Electrophoretic separation of viral nucleic acids on polyacrylamide gels. J Mol Biol. 1967 Jun 28;26(3):373–387. doi: 10.1016/0022-2836(67)90310-5. [DOI] [PubMed] [Google Scholar]
- Bishop D. H., Mills D. R., Spiegelman S. The sequence at the 5' terminus of a self-replicating variant of viral Q-beta ribonucleic acid. Biochemistry. 1968 Oct;7(10):3744–3753. doi: 10.1021/bi00850a056. [DOI] [PubMed] [Google Scholar]
- Haruna I., Spiegelman S. Specific template requirments of RNA replicases. Proc Natl Acad Sci U S A. 1965 Aug;54(2):579–587. doi: 10.1073/pnas.54.2.579. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Levisohn R., Spiegelman S. The cloning of a self-replicating RNA molecule. Proc Natl Acad Sci U S A. 1968 Jul;60(3):866–872. doi: 10.1073/pnas.60.3.866. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mills D. R., Peterson R. L., Spiegelman S. An extracellular Darwinian experiment with a self-duplicating nucleic acid molecule. Proc Natl Acad Sci U S A. 1967 Jul;58(1):217–224. doi: 10.1073/pnas.58.1.217. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pace N. R., Spiegelman S. In vitro synthesis of an infectious mutant RNA with a normal RNA replicase. Science. 1966 Jul 1;153(3731):64–67. doi: 10.1126/science.153.3731.64. [DOI] [PubMed] [Google Scholar]
- Pace N. R., Spiegelman S. The synthesis of infectious RNA with a replicase purified according to its size and density. Proc Natl Acad Sci U S A. 1966 Jun;55(6):1608–1615. doi: 10.1073/pnas.55.6.1608. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sanger F., Brownlee G. G., Barrell B. G. A two-dimensional fractionation procedure for radioactive nucleotides. J Mol Biol. 1965 Sep;13(2):373–398. doi: 10.1016/s0022-2836(65)80104-8. [DOI] [PubMed] [Google Scholar]