Endy Drew. You Lingchong. Yin John. Molineux Ian J.
Computation, prediction, and experimental tests of fitness for bacteriophage
T7 mutants with permuted genomes, Proceedings of the National Academy of Sciences of the United States of
America 97(10) :5375-5380, 2000.
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 105 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.
Return to In Silico Biology References