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Gene structure and expression
TIBS 11 - January 1986
54 noncovalent interactions between functional groups on the protein; and (3) provide a test of the predictions from model building based on the individual structures. It is also important to recognize what information about biopolymers and their complexes is not available from structural studies. In general, only limited information about dynamics can be obtained, using crystallographic thermal factors. At high levels of refinement, the positions of some water molecules and counterions in the crystal can be deduced, but there is in general no reason to expect that water and counterions will be similarly localized in a dilute solution. Indeed both hydration and counterion association with polyions in solution are
thermodynamic concepts, involving preferential interactions which, while thermodynamically equivalent to binding, neither imply nor require site binding as a correponding molecular picture. Whereas there is ample precedent for believing that the structure of a biopolymer in the low-water-activity environment of a crystal accurately reflects the average solution structure, no similar precedent exists for the solvent and counterions. Finally, since the entropic consequences of changes in the preferential interactions of water and ions with biopolymers in conformational transitions or association reactions provide much of the driving force for these processes in solution, it is unreasonable to
/ ~ s f i f i e d genes Gene Structure and Expression by John D. Hawkins, Cambridge University Press, 1985. £7.95/$14.95 (xii + 173 pages) ISBN 0 521 27726 4 [also available in hardback] It was at one time difficult to find textbooks covering the dramatic developments in our understanding of genes. The explosion of information was of course due to the arrival of recombinant DNA, and it took time for the new technology and all its consequences to filter through to the undergraduate literature. Nowadays there are several books designed for undergraduate courses. This one is aimed primarily at medical students and emphasizes biochemical rather than classically genetic aspects of genes. There are problems with this book. It lacks 'sweep', concentrating on detail, with little of the biological contextinto which the detail may be fitted. This, together with a somewhat laboured writing style, makes concentration difficult. The chapter on hormone genes, to give one example, is sometimes little more than a list of facts about the structure of various genes. The facts as described reveal few general principles, except perhaps that this form of presentation is dull in the extreme. The illustrations do not help. Most are minimal line drawings, sometimes poorly executed, often cluttered with letters and abbreviations. Curiously, all figures abutt the bottom of the page with the legend above the figure rather than below it. When two figures appear on a page, they are stacked one
expect to be able to deduce thermodynamic information from structural studies. Thermodynamic and mechanistic information about the conformational transitions and interactions of biopolymers is only obtainable from equilibrium and kinetic studies in solution. Structural information from crystallography provides the detailed molecular framework for interpretation of these solution studies. To relate biopolymer structure to function, detailed thermodynamic and kinetic studies under physiologically relevant solution conditions are required. M. THOMAS RECORD, JR
Departments of Chemistry and Biochemistry, University of Wisconsin, Madison, W153706, USA.
the long direct repeats are looped out like enormous balloons tethered by their above the other (legends upper-most), base-paired inverted repeats (the gal appearing by their combined weight to operon looks similar except that identipush the bottom figure off altogether. cal bases are now allowed to pair). These weaknesses detract from the Neither the legends nor text indicate that book, but are nothing compared to seri- any assumptions have been made in repous errors in the treatment of some basic resenting them in this preposterous way. topics. D N A replication is explained Comparatively minor misconceptions with the aid of two diagrams occupying a abound. For example, that DNA must whole page. Each diagram shows a repli- always be denatured before analysis on cation fork in which all newly syn- agarose or acrylamide gels (high salt is thesized DNA strands are growing in the apparently one way of achieving this), or wrong direction (3' to 5'). This is a fun- that introns are widely thought to funcdamental error in such a book, but if any- tion as a valuable pool of DNA from thing, transcription fares less well. The which new genes can evolve by mutavisual aid in this case (Figure 5.2) lacks tion. Finally there are surprising omissions clarity to a degree which is scarcely believable. There is, of course, the well- for a book with this title. Some of the known electron micrograph of transcrip- best studied genes (thymidine kinase, tion in E. coli (Figure 2.12), showing lat- heat shock and DNA virus genes) are not eral transcripts of increasing lengths mentioned. We hear that T A T A boxes along a D N A strand. Each of eight trans- are important, but no inkling is given cripts is associated with multiple ribo- about how this was established. Systems somes. The figure, however, is labelled for transcriptional assay (frog oocytes, 'Electron micrograph of a polysome', giv- transient expression, transformation, ing the unmistakable impression that the mouse embryo injection, cell extracts) D N A strand should be regarded as do not rate discussion. RNA, and the RNA as protein. TransI confess to a feeling of indignation cription is not mentioned. Misgivings that this book, from a major publisher of about the author's view of transcription educational books, should purport to are heightened in the section on $1 map- give students an insight into the fasping, a technique that is, according to the cinating subject of gene structure and author, useful for establishing 'the 3' end expression. My advice to students is: at which transcription began'. The illus- buy a different book. trated description misses the point of $1 ADRIAN P. BIRD mapping completely by falsely claiming that the labelled probe is also the template for transcription. What is more, it shows transcription giving rise to a long R N A - D N A hybrid. MRC Mammalian Genome Unit, Department of Then there is the diagram of a trans- Zoology, Universityof Edinburgh, West Mains Rd, posable element (Figure 8.2) in which Edinburgh EH9 3JT, UK.
54 noncovalent interactions between functional groups on the protein; and (3) provide a test of the predictions from model building based on the individual structures. It is also important to recognize what information about biopolymers and their complexes is not available from structural studies. In general, only limited information about dynamics can be obtained, using crystallographic thermal factors. At high levels of refinement, the positions of some water molecules and counterions in the crystal can be deduced, but there is in general no reason to expect that water and counterions will be similarly localized in a dilute solution. Indeed both hydration and counterion association with polyions in solution are
thermodynamic concepts, involving preferential interactions which, while thermodynamically equivalent to binding, neither imply nor require site binding as a correponding molecular picture. Whereas there is ample precedent for believing that the structure of a biopolymer in the low-water-activity environment of a crystal accurately reflects the average solution structure, no similar precedent exists for the solvent and counterions. Finally, since the entropic consequences of changes in the preferential interactions of water and ions with biopolymers in conformational transitions or association reactions provide much of the driving force for these processes in solution, it is unreasonable to
/ ~ s f i f i e d genes Gene Structure and Expression by John D. Hawkins, Cambridge University Press, 1985. £7.95/$14.95 (xii + 173 pages) ISBN 0 521 27726 4 [also available in hardback] It was at one time difficult to find textbooks covering the dramatic developments in our understanding of genes. The explosion of information was of course due to the arrival of recombinant DNA, and it took time for the new technology and all its consequences to filter through to the undergraduate literature. Nowadays there are several books designed for undergraduate courses. This one is aimed primarily at medical students and emphasizes biochemical rather than classically genetic aspects of genes. There are problems with this book. It lacks 'sweep', concentrating on detail, with little of the biological contextinto which the detail may be fitted. This, together with a somewhat laboured writing style, makes concentration difficult. The chapter on hormone genes, to give one example, is sometimes little more than a list of facts about the structure of various genes. The facts as described reveal few general principles, except perhaps that this form of presentation is dull in the extreme. The illustrations do not help. Most are minimal line drawings, sometimes poorly executed, often cluttered with letters and abbreviations. Curiously, all figures abutt the bottom of the page with the legend above the figure rather than below it. When two figures appear on a page, they are stacked one
expect to be able to deduce thermodynamic information from structural studies. Thermodynamic and mechanistic information about the conformational transitions and interactions of biopolymers is only obtainable from equilibrium and kinetic studies in solution. Structural information from crystallography provides the detailed molecular framework for interpretation of these solution studies. To relate biopolymer structure to function, detailed thermodynamic and kinetic studies under physiologically relevant solution conditions are required. M. THOMAS RECORD, JR
Departments of Chemistry and Biochemistry, University of Wisconsin, Madison, W153706, USA.
the long direct repeats are looped out like enormous balloons tethered by their above the other (legends upper-most), base-paired inverted repeats (the gal appearing by their combined weight to operon looks similar except that identipush the bottom figure off altogether. cal bases are now allowed to pair). These weaknesses detract from the Neither the legends nor text indicate that book, but are nothing compared to seri- any assumptions have been made in repous errors in the treatment of some basic resenting them in this preposterous way. topics. D N A replication is explained Comparatively minor misconceptions with the aid of two diagrams occupying a abound. For example, that DNA must whole page. Each diagram shows a repli- always be denatured before analysis on cation fork in which all newly syn- agarose or acrylamide gels (high salt is thesized DNA strands are growing in the apparently one way of achieving this), or wrong direction (3' to 5'). This is a fun- that introns are widely thought to funcdamental error in such a book, but if any- tion as a valuable pool of DNA from thing, transcription fares less well. The which new genes can evolve by mutavisual aid in this case (Figure 5.2) lacks tion. Finally there are surprising omissions clarity to a degree which is scarcely believable. There is, of course, the well- for a book with this title. Some of the known electron micrograph of transcrip- best studied genes (thymidine kinase, tion in E. coli (Figure 2.12), showing lat- heat shock and DNA virus genes) are not eral transcripts of increasing lengths mentioned. We hear that T A T A boxes along a D N A strand. Each of eight trans- are important, but no inkling is given cripts is associated with multiple ribo- about how this was established. Systems somes. The figure, however, is labelled for transcriptional assay (frog oocytes, 'Electron micrograph of a polysome', giv- transient expression, transformation, ing the unmistakable impression that the mouse embryo injection, cell extracts) D N A strand should be regarded as do not rate discussion. RNA, and the RNA as protein. TransI confess to a feeling of indignation cription is not mentioned. Misgivings that this book, from a major publisher of about the author's view of transcription educational books, should purport to are heightened in the section on $1 map- give students an insight into the fasping, a technique that is, according to the cinating subject of gene structure and author, useful for establishing 'the 3' end expression. My advice to students is: at which transcription began'. The illus- buy a different book. trated description misses the point of $1 ADRIAN P. BIRD mapping completely by falsely claiming that the labelled probe is also the template for transcription. What is more, it shows transcription giving rise to a long R N A - D N A hybrid. MRC Mammalian Genome Unit, Department of Then there is the diagram of a trans- Zoology, Universityof Edinburgh, West Mains Rd, posable element (Figure 8.2) in which Edinburgh EH9 3JT, UK.