Methodology in Basic Genetics

By Walter J. Burdette | Go to book overview

Ernst Freese, Ph.D.


INDUCED and SPONTANEOUS MUTATIONS in BACTERIOPHAGE

The aim of mutagenic work with phages is twofold: to determine with which relative frequency the different types of mutagenic base-pair changes in DNA occur spontaneously, which of them can be induced artificially, and how these changes come about in detail; to analyze for such mutants the detailed structural alteration of other molecules (RNA, proteins) in relation to the various base-pair changes. This paper will be concerned only with the first approach since work on the second aspect is just beginning.

The following base-pair changes in DNA are conceivable: replacements of one or more base pairs by other base pairs, deletions, insertions (additions of one or more base pairs), and inversions. Single base-pair replacements can be subdivided into transitions, the exchange of one purine by the other purine and one pyrimidine by the other pyrimidine, and transversions, the exchange of a purine by a pyrimidine and vice versa.288

Since the spontaneous mutagenic mechanisms are unknown, it is mandatory to proceed indirectly as follows: (1) use mutagens with chemical action which is either known or determinable by present chemical means; (2) surmise from this chemical effect and the mode of DNA duplication which base-pair changes a particular agent can induce; (3) show that genetic experiments employing this mutagen agree with the chemical expectation; (4) compare the genetic properties of spontaneous mutations, or mutations induced by an agent whose chemical effect is not well understood, with the genetic properties of those mutations whose base-pair changes have been determined previously. If these properties differ for mutations of different origin, the mutagenic mechanism must be different; otherwise it may be similar or identical. Understanding

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