NDLI: Computation, prediction, and experimental tests of fitness for bacteriophage T7 mutants with permuted genomes.

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Computation, prediction, and experimental tests of fitness for bacteriophage T7 mutants with permuted genomes.

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Computation, prediction, and experimental tests of fitness for bacteriophage T7 mutants with permuted genomes.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Endy, D. You, L. Yin, J. Molineux, I. J.
Description	Author Affiliation: Endy D ( The Molecular Sciences Institute, 2168 Shattuck Avenue, Berkeley, CA 94704, USA. dendy@molsci.org);
Abstract	We created a simulation based on experimental data from bacteriophage T7 that computes the developmental cycle of the wild-type phage and also of mutants that have an altered genome order. We used the simulation to compute the fitness of more than 10(5) mutants. We tested these computations by constructing and experimentally characterizing T7 mutants in which we repositioned gene 1, coding for T7 RNA polymerase. Computed protein synthesis rates for ectopic gene 1 strains were in moderate agreement with observed rates. Computed phage-doubling rates were close to observations for two of four strains, but significantly overestimated those of the other two. Computations indicate that the genome organization of wild-type T7 is nearly optimal for growth: only 2.8% of random genome permutations were computed to grow faster, the highest 31% faster, than wild type. Specific discrepancies between computations and observations suggest that a better understanding of the translation efficiency of individual mRNAs and the functions of qualitatively 'nonessential' genes will be needed to improve the T7 simulation. In silico representations of biological systems can serve to assess and advance our understanding of the underlying biology. Iteration between computation, prediction, and observation should increase the rate at which biological hypotheses are formulated and tested.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	10
Volume Number	97
Language	English
Publisher	National Academy of Sciences
Publisher Date	2000-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Bacteriophage T7 Genetics DNA-Directed RNA Polymerases Genome, Viral Models, Genetic Mutagenesis Enzymology Growth & Development Escherichia Coli Virology Genes, Viral Reproducibility Of Results Viral Proteins Viral Structural Proteins Research Support, U.S. Gov't, Non-P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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