MAPPING EXPERIMENTS WITH r MUTANTS OF BACTERIOPHAGE T4D

Edgar, R. S.; Feynman, Richard P.; Klein, Sabine; Lielausis, I.; Steinberg, Charles M.

doi:10.1093/genetics/47.2.179

Cited by 56 publications

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“…Map contraction in the X-ray crosses of widely separated mutants resembles what is observed in genetic fine structure maps of bacteria and phage (STREI-SINGER and FRANKLIN 1956;BENZER 1957;CHASE and DOERMAN 1958;YANOF-SKY 1960;GAREN 1960;EDGAR et al 1962;AMATI and MESELSON 1965;FISHER and BERNSTEIN 1965). Likewise the difficulty in ordering closely linked mutants on the X-ray maps recalls the non-linearity of recombination frequencies observed by TESSMAN (1965) in attempting to order closely linked sites of the rll locus of phage T4.…”

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confidence: 56%

X-RAY AND MEIOTIC FINE STRUCTURE MAPPING OF THE ADENINE-8 LOCUS IN SACCHAROMYCES CEREVISIAE

Esposito

1968

Genetics

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W -H I L E it has been demonstrated in a variety of organisms that genes differ in their spontaneous mutation rates, little is known concerning the basis of these differences. Since the spontaneous mutations affecting adenine biosynthesis in Saccharomyces cerevisiae can be obtained by a selective technique (ROMAN l956), they provide a convenient system in which to study the factors involved in spontaneous mutation rates. In this yeast there are two adenine requiring mutants, adenine-I and adenine-2, which produce a red pigment as a result of the block in adenine synthesis. Haploid cultures of either adenine-I or adenine-2 accumulate white and pink mutants which outgrow the parental red strains. Genetic analysis of these color variants has shown that the interference with pigment production is most often the result of a second mutation in the adenine pathway.The mutants thus obtained are unequally distributed among six loci (ROMAN 1956; JONES 1964). The question of this differential mutability at the adenine loci has been examined by JONES (1 964) in a comparative study of the adenine-3 and adenine-6 loci. The results of her study indicated that there was a positive correlation between the size of these loci, measured by their recombinational lengths and numbers of mutable sites, and the frequency with which they give rise to spontaneous mutations. The twofold difference in the size of these loci, however, was not sufficient to explain the five to tenfold higher mutability of adenine-6 as compared with adenine-3. Further study of the properties of the mutants of each of these loci led to the suggestion that this discrepancy might be due to the failure to recover a substantial fraction of adenine-3 mutants, i.e., that the mutation frequency of adenine-3 is actually higher than is observed.The adenine-8 locus was chosen for investigation in this study because mutants of this gene occur with approximately the same frequency as those of the adenine-3 locus but their properties do not suggest that a large number of mutations are not being recovered. Accordingly adenine-8 should be smaller than adenine-3 and adenine-6, in terms of both recombinational length and number of mutable sites, if gene size is an important component of mutation frequency.In this study the recombinational length of the adenine-8 locus was estimated by two independent methods of allelic mapping. A meiotic fine structure map was constructed using allelic recombination frequencies after meiosis as a meas-1 Supported by Grants 5 R01-AI00328 and 5 TO1-GZI 00328 of the

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confidence: 56%

X-RAY AND MEIOTIC FINE STRUCTURE MAPPING OF THE ADENINE-8 LOCUS IN SACCHAROMYCES CEREVISIAE

Esposito

1968

Genetics

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“…In the T4rZZ system, for instance, 809 of the first 1609 independently isolated mutants were observed to map into only two sites (BEN-ZER 1961). Genetic data indicate that the number of rZZ sites capable of mutation by base pair substitution is about 1700 (EDGAR et al 1962;STAHL, EDGAR and STEINBERG 1964), and this estimate is supported by quasi-chemical measurements (GOLDBERG 1966). When frameshift mutations are excluded from consideration, however, fewer than 3% of these potential sites have been identified (FREESE 1959;BENZER 1961;ORGEL and BRENNER 1961; see Chapter 5 of DRAKE 1970).…”

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confidence: 83%

Cryptic Mutants of Bacteriophage T4

Koch¹,

Drake²

1970

Genetics

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HE apparent mutation rate depends upon a number of contingencies: the Tprimary error rate, the probability o€ repair, error avoidance by the apparatus of DNA replication, and the probability of detection. The probability of detection of those base pair substitutions which produce an amino acid substitution appears to be highly variable, and presumably reflects the sensitivity of polypeptide functions to small variations in primary structure.Fine-scale mapping has often revealed a highly nonrandom distribution of mutations among sites. In the T4rZZ system, for instance, 809 of the first 1609 independently isolated mutants were observed to map into only two sites (BEN-ZER 1961). Genetic data indicate that the number of rZZ sites capable of mutation by base pair substitution is about 1700 (EDGAR et al. 1962;STAHL, EDGAR and STEINBERG 1964), and this estimate is supported by quasi-chemical measurements (GOLDBERG 1966). When frameshift mutations are excluded from consideration, however, fewer than 3% of these potential sites have been identified (FREESE 1959;BENZER 1961;ORGEL and BRENNER 1961; see Chapter 5 of DRAKE 1970). What then is the nature of the apparently immutable sites?Two possible answers deserve serious consideration: many sites are extremely weakly mutable, or else many amino acid substitutions are undetected in standard screening systems because they fail to exert significantly deleterious effects upon protein function. The first possibility is supported by the observation that

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“…Feynman's work consisted in mapping a reasonably large number of rII markers in a second phage strain, the T4D one (Edgar et al 1962). By analyzing back-mutants that were evidently not completely normal, he realized that such back-mutants had both the r 43 mutation and a second mutation that somewhat enhanced its effects.…”

Section: Plus and Minus Classes: Feynman At Caltechmentioning

confidence: 99%

“…Feynman's interest in biology began around 1959, and culminated in the publication of a relevant paper on genetics in 1962 (Edgar et al 1962). His peculiar guiding view was that "there is nothing that living things do that cannot be understood from the point of view that they are made of atoms according to the laws of physics" (Feynman, Leighton and Sands 2005).…”

Section: Introductionmentioning

confidence: 99%

“…Given the relevant results he obtained, Feynman was invited to give a seminar on his work at Harvard, where he met James Watson, Francis Crick and others. Interesting enough, a key paper by Crick et al (1961) quoted Feynman's work with Edgar, which was then published in 1962 (Edgar et al 1962). In the present paper, we dwell just on Feynman's incursions in the field of biology, by focusing on his work on genetics with Edgar as well as on his lectures at Hughes Company about biology, organic chemistry and microbiology.…”

Section: Introductionmentioning

confidence: 99%

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When physics meets biology: a less known Feynman

Mauro¹,

Esposito²,

Naddeo³

2019

Società Italiana Degli Storici Della Fisica E Dell'Astronomia. Atti Del XXXVII Convegno Annuale / Proceedings of the 37th Annua

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We discuss a less known aspect of Feynman's multifaceted scientific work, centered about his interest in molecular biology, which came out around 1959 and lasted for several years. After a quick historical reconstruction about the birth of molecular biology, we focus on Feynman's work on genetics with Robert S. Edgar in the laboratory of Max Delbruck, which was later quoted by Francis Crick and others in relevant papers, as well as in Feynman's lectures given at the Hughes Aircraft Company on biology, organic chemistry and microbiology, whose notes taken by the attendee John Neer are available. An intriguing perspective comes out about one of the most interesting scientists of the XX century.

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MAPPING EXPERIMENTS WITH r MUTANTS OF BACTERIOPHAGE T4D

Cited by 56 publications

References 0 publications

X-RAY AND MEIOTIC FINE STRUCTURE MAPPING OF THE ADENINE-8 LOCUS IN SACCHAROMYCES CEREVISIAE

X-RAY AND MEIOTIC FINE STRUCTURE MAPPING OF THE ADENINE-8 LOCUS IN SACCHAROMYCES CEREVISIAE

Cryptic Mutants of Bacteriophage T4

When physics meets biology: a less known Feynman

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