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On the Topology of the Genetic Fine Structure

Benzer, Seymour (1959) On the Topology of the Genetic Fine Structure. Proceedings of the National Academy of Sciences of the United States of America, 45 (11). pp. 1607-1620. ISSN 0027-8424. PMCID PMC222769. doi:10.1073/pnas.45.11.1607.

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From the classical researches of Morgan and his school [1], the chromosome is known as a linear arrangement of hereditary elements, the "genes." These elements must have an internal structure of their own. At this finer level, within the "gene" the question arises again: what is the arrangement of the sub-elements? Specifically, are they linked together in a linear order analogous to the higher level of integration of the genes in the chromosome? Until recently, the sensitivity of genetic analysis has been insufficient to answer this question. Mapping of a genetic structure is done by observing the recombination of its parts, and recombination involving parts of the structure that are very close together is a rare event. Observation of such rare events requires very many offspring and a selective trick for detecting the few individuals in which the event is recorded. It is for this reason that microorganism are the material of choice for studies of genetic fine structure, and have made it feasible to extend the fineness of genetic mapping by orders of magnitude. In favorable systems, the attainable resolution reaches the level of the molecular subunits of the hereditary material. and experimental testing of the linear arrangement of the finest structural details is therefore possible. A number of cases have been investigated on this level [2]. As a rule, closely linked mutations affecting the same characteristic can be seriated in an unambiguous way, suggesting a linear model. However, the "distances" (i.e., recombination frequencies) between mutations are not always strictly additive, and certain complexities ("negative interference" effects [3,4]) make quantitative analysis difficult. As pointed out by Muller [5] in regard to similar difficulties encountered in mapping on the chromosomal level, strict additivity of "distances" should not be taken as the criterion for the linear character of an array. A crucial examination of the question should be made from the point of view of topology, since it is a matter of how the parts of the structure are connected to each other, rather than of the distances between them. Experiments to explore the topology should ask qualitative questions (e.g., do two parts of the structure touch each other or not?) rather than quantitative ones (how far apart are they?). In what follows, such an investigation is attempted for a small portion of the genetic structure of a virus, the "rII" region of phage T4. Using only qualitative tests, an examination is made of the topology of this structure at the molecular level.

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Additional Information:© 1959 by the National Academy of Sciences Communicated by M. Delbrück, September 8, 1959 I am indebted to Mrs. Marion Sjodin for assistance in the isolation of many of the mutants, to Dr. Leslie Orgel of Cambridge University for suggesting the "dictionary order" analogy, and to Dr. Max Delbrück for suggestions regarding the possibility of branches and for his usual moderating influence. This work was assisted by grants from the National Science Foundation and the National Institutes of Health.
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Issue or Number:11
PubMed Central ID:PMC222769
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Official Citation:ON THE TOPOLOGY OF THE GENETIC FINE STRUCTURE Seymour Benzer Proceedings of the National Academy of Sciences Nov 1959, 45 (11) 1607-1620; DOI: 10.1073/pnas.45.11.1607
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:6179
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Deposited On:28 Nov 2006
Last Modified:08 Nov 2021 20:31

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