Cell
Volume 13, Issue 4, April 1978, Pages 735-744
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Nucleotide sequence heterogeneity of an RNA phage population

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Abstract

The nucleotide sequence of 32P-RNA from Qβ phage clones was sampled by two-dimensional polyacrylamide gel electrophoresis of the RNAase T1-resistant oligonucleotides (T1 fingerprinting). About 15% of the clones derived from a multiply passaged Qβ population showed fingerprint patterns which deviated from that of the RNA from the total population. All deviations examined could be attributed to one and, less frequently, to two or more nucleotide transitions. Since the fingerprinting technique allows the analysis of only about 10% of the RNA sequence, we estimate that each viable phage genome in a multiply passaged population differs in one to two positions from the “average” sequence of the parental population. Several deviant clones were tested by growth competition against a “wild-type” population; after 10–20 generations, the resulting phage showed the “wild-type” T1 fingerprint pattern. We propose that a Qβ phage population is in a dynamic equilibrium, with viable mutants arising at a high rate (Batschelet, Domingo and Weissmann, 1976; Domingo, Flavell and Weissmann, 1976) on the one hand, and being strongly selected against on the other. The genome of Qβ phage cannot be described as a defined unique structure, but rather as a weighted average of a large number of different individual sequences.

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Present address: Centro de Biologia Molecular, Universidad Autónoma de Madrid, Canto Blanco, Madrid, Spain.

This work was initiated by D. S. and completed after her untimely death in 1976.

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