On the Colinearity of Gene Structure and Protein Structure

Yanofsky, Charles; Carlton, Bruce C.; Guest, John R.; Helinski, Donald R.; Henning, Ulf

doi:10.1073/pnas.51.2.266

Cited by 239 publications

(53 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The first system in which this was actually tested was the tryptophan synthetase A gene in Escherichia coli (20). The results of that study indicated that the genetic fine-structure map was indeed colinear with the protein structure.…”

mentioning

confidence: 75%

Mutations at theSaccharomyces cerevisiae SUP4tRNA^TyrLocus: Isolation, Genetic Fine-Structure Mapping, and Correlation with Physical Structure

Kurjan¹,

Hall²

1982

Mol. Cell. Biol.

View full text Add to dashboard Cite

The SUP4 tRNATYr locus in Saccharomyces cerevisiae has been studied by the isolation and characterization of mutations at the SUP4 gene which result in the loss of suppressor function. Most of the mutations act as single-site mutations, whereas about a third of the mutations are deletions of the entire gene. Two meiotic fine-structure maps of the gene were made. The first mapping technique placed 10 mutations plus the sup4+ anticodon on a map by a measurement of levels of recombination between pairs of mutations. The second map utilized a more qualitative estimate of recombination frequency, allowing 69 mutations and the sup4+ anticodon to be mapped. The maps were compared with the physical structure of the gene for the 34 mutations whose nucleotide alteration has been determined by DNA sequencing (Koski et al., Cell 22:415-425, 1980; Kurjan et al., Cell 20:701-709, 1980). Both maps show a good correlation with the physical structure of the gene, even though certain properties of genetic fine-structure maps, such as marker effects and "map expansion," were seen.The use of genetic fine-structure mapping to order mutations within a gene has been based on the assumption that the recombination frequency between two mutations is proportional to the nucleotide distance between them. The first system in which this was actually tested was the tryptophan synthetase A gene in Escherichia coli (20). The results of that study indicated that the genetic fine-structure map was indeed colinear with the protein structure.Since that time, it has become clear that finestructure mapping in lower eucaryotic systems is subject to several features that put the accuracy of fine-structure maps into doubt. In yeasts, it has been found that both meiotic and mitotic Xray fine-structure maps show "map expansion" (2, 3, 6, 9), a property initially defined by Holliday (7) in which, given a map order abc, the recombination frequency between ac is larger than that of the summed frequencies ab + bc. This property of map expansion indicates that the assumption that recombination frequency is proportional to DNA distance is not strictly true. Fine-structure mapping data also often show marker effects, in which a particular marker may give unusually high or low levels of recombination with other markers (3, 6). Such marker effects will also lead to inaccuracies in the fine-structure map. Finally, an extensive study by Moore and Sherman (13,14) indicated that the level of recombination per nucleotide could vary extensively between different pairs of mutations. These studies utilized a large number of mutations within the Saccharomyces cerevisiae cycl gene for which the physical location of the mutations were known. Even two different mutations at the same site could give quite different levels of recombination with another mutation. This effect was significant enough to lead to improper ordering of mutations with respect to one another in some cases. Although this effect was shown to be significantly less extreme for meiotic recombination frequen...

show abstract

mentioning

confidence: 75%

Mutations at theSaccharomyces cerevisiae SUP4tRNA^TyrLocus: Isolation, Genetic Fine-Structure Mapping, and Correlation with Physical Structure

Kurjan¹,

Hall²

1982

Mol. Cell. Biol.

View full text Add to dashboard Cite

show abstract

“…By 1964 we had convincingly shown that the order of mutational changes on the genetic map of the trpA gene was colinear with the order of amino acid changes in the TrpA protein (24,25). Our deduced colinear relationship is shown in Figure 2.…”

Section: My Primary Focus-establishing Gene-protein Colinearitymentioning

confidence: 99%

Advancing Our Knowledge in Biochemistry, Genetics, and Microbiology Through Studies on Tryptophan Metabolism

Yanofsky

2001

Annu. Rev. Biochem.

View full text Add to dashboard Cite

I was fortunate to practice science during the last half of the previous century, when many basic biological and biochemical concepts could be experimentally addressed for the first time. My introduction to research involved isolating and identifying intermediates in the niacin biosynthetic pathway. These studies were followed by investigations focused on determining the properties of genes and enzymes essential to metabolism and examining how they were alterable by mutation. The most challenging problem I initially attacked was establishing the colinear relationship between gene and protein. Subsequent research emphasized identification and characterization of regulatory mechanisms that microorganisms use to control gene expression. An elaborate regulatory strategy, transcription attenuation, was discovered that is often based on selection between alternative RNA structures. Throughout my career I enjoyed the excitement of solving basic scientific problems. Most rewarding, however, was the feeling that I was helping young scientists experience the pleasure of performing creative research. CONTENTS

show abstract

“…Dounce (1952) and Gamow (1954) independently presented the so-called colinearity hypothesis, according to which the linear structure of DNA determines the linear primary structure of a polypeptide. The colinearity hypothesis was shown to be true by Sarabhai et al (1964) and Yanofsky et al (1964Yanofsky et al ( , 1967, by comparing the genetic map of the T4 phage coat protein gene and the corresponding primary structure of the polypeptide, and also by comparing the genetic map of the tryptophane synthetase gene of Escherichia coli with the corresponding primary structure of the polypeptide. In other words, Yanofsky's group demonstrated the co-linearity of mutant nucleotide sites and the corresponding mutated aminoacyl polypeptide sites.…”

Section: Conceptions Of the Genementioning

confidence: 99%

Historical Development of the Concept of the Gene

Portin

2002

The Journal of Medicine and Philosophy

View full text Add to dashboard Cite

The classical view of the gene prevailing during the 1910s and 1930s comprehended the gene as the indivisible unit of genetic transmission, genetic recombination, gene mutation and gene function. The discovery of intragenic recombination in the early 1940s led to the neoclassical concept of the gene, which prevailed until the 1970s. In this view the gene or cistron, as it was now called, was divided into its constituent parts, the mutons and recons, materially identi®ed as nucleotides. Each cistron was believed to be responsible for the synthesis of one single mRNA and concurrently for one single polypeptide. The discoveries of DNA technology, beginning in the early 1970s, have led to the second revolution in the concept of the gene in which none of the classical or neoclassical criteria for the de®nition of the gene hold strictly true. These are the discoveries concerning gene repetition and overlapping, movable genes, complex promoters, multiple polyadenylation sites, polyprotein genes, editing of the primary transcript, pseudogenes and gene nesting. Thus, despite the fact that our comprehension of the structure and organization of the genetic material has greatly increased, we are left with a rather abstract, open and general concept of the gene. This article discusses past and present contemplations of genes, genomes, genotypes and phenotypes as well as the most recent advances of the study of the organization of genomes.

show abstract

On the Colinearity of Gene Structure and Protein Structure

Cited by 239 publications

References 12 publications

Mutations at theSaccharomyces cerevisiae SUP4tRNA^TyrLocus: Isolation, Genetic Fine-Structure Mapping, and Correlation with Physical Structure

Mutations at theSaccharomyces cerevisiae SUP4tRNA^TyrLocus: Isolation, Genetic Fine-Structure Mapping, and Correlation with Physical Structure

Advancing Our Knowledge in Biochemistry, Genetics, and Microbiology Through Studies on Tryptophan Metabolism

Historical Development of the Concept of the Gene

Contact Info

Product

Resources

About

On the Colinearity of Gene Structure and Protein Structure

Cited by 239 publications

References 12 publications

Mutations at theSaccharomyces cerevisiae SUP4tRNATyrLocus: Isolation, Genetic Fine-Structure Mapping, and Correlation with Physical Structure

Mutations at theSaccharomyces cerevisiae SUP4tRNATyrLocus: Isolation, Genetic Fine-Structure Mapping, and Correlation with Physical Structure

Advancing Our Knowledge in Biochemistry, Genetics, and Microbiology Through Studies on Tryptophan Metabolism

Historical Development of the Concept of the Gene

Contact Info

Product

Resources

About

Mutations at theSaccharomyces cerevisiae SUP4tRNA^TyrLocus: Isolation, Genetic Fine-Structure Mapping, and Correlation with Physical Structure

Mutations at theSaccharomyces cerevisiae SUP4tRNA^TyrLocus: Isolation, Genetic Fine-Structure Mapping, and Correlation with Physical Structure