1. 1. Aspects of development. usually competent to develop in several differ- If you have been fortunate enough to see a fIlm ent ways. Thus the mesenchyme cells of the of the development of any multicellular organ- embryonic chick limb bud may become, among ism or, better still, to watch live embyros devel- other things, muscle or cartilage cells. Differen- oping, the intricate beauty of the developmental tiation is largely an intracellular process involv- process will not have escaped you: nor will its ing the appearance of cells with certain bio- complexity. Apparent complexity, however, is chemically or cytologically recognizable charac- no reason for despair when one begins to think teristics through the differential activation of in terms of analysing development. Rather, it is genes whose products confer these character- istics on the cello In skeletal muscle cells for astimulus to the first and most important ana- lytical step, that of simplifying the problem by example, specific proteins (actin and myosin) dividing it into aspects which can be meaning- are synthesized, and arranged to give the typical fully studied. striated appearance (Fig. l. la).(Differentiation is the subject of another book in this series, The most obvious way to divide development is on a chronological basis - to begin with ferti- 'Cell Differentiation' by J. M. Ashworth. ) lization and proceed through cleavage, blastu- Recent advances in molecular biology have greatly stimulated research into differentiation lation and gastrulation to organ fromation.

The development of an embryo is one of the which prevents entry of other sperm, fusion of most awe inspiring biological phenomena and the two haploid nuclei occurs and within about the study of cell differentiation can be traced 30 minutes the pigmented cortex rotates with respect to the underlying cytoplasm and in so back in antiquity to Aristotle and beyond However, there are few modern sciences which doing it reveals a grey, crescent shaped area on pay more than a cursory obeisance to their the side of the egg opposite to the point of founders and few students seem very interested entry of the sperm. This is another example of in the theories of their dead predecessors. polarity developing. Soon after fertilization the Embryology, though, is that rare exception - a zygote enters a period of rapid nuclear and cell division. The result of this cleavage process is science where the problems, theories and often that the egg cytoplasm is partitioned between techniques that excite our interest today, are essentially the same as those which excited our numerous cells whose ratio of nuclear volume to cytoplasmic volume is more like that found colleagues of fifty or even a hundred years ago. in an 'average' somatic cell.

1. 1 Historical development of molecular virology of effort on a limited number of phages, Viruses have occupied a central position in notably the Escherichia coli phages T2 and T4. molecular biology ever since its development as At the same time Lwoff and his colleagues were an independent discipline. Indeed, molecular studying phage A, a temperate phage of E. coli, biology itselflargely developed out of the work which was to lead to equally fundamental pioneer studies of Delbriick, Luria and Hershey, observations on the regulation of macro­ who realized, in the late 1930's, that bacterial molecular synthesis. viruses (bacteriophages, often abbreviated to The study of animal and plant viruses has its phages) had properties which made them origins in the latter half of the 19th century uniquely suitable as a model system for an and was largely initiated by workers in medical, attack on one of the then outstanding problems veterinary and agricultural disciplines. Many of of biology, the definition of the gene in their practical successes owe little to molecular physical and chemical terms. The favourable biology, stemming instead from those properties of these viruses include the rapidity approaches successful in combating other of their growth, their ease of assay, and the parasites, such as vector control and the availability of easily scored genetic markers. breeding of resistant varieties of plants.

The brain is the most complex and highly of semi-permeable excitable membranes which specialised of all mammalian organs. Under­ can be caused, rapidly and transiently, to under­ standing the complexity of its function remains go changes in permeability to small chemical man's greatest challenge. The functional unit is molecules and to cations. The highly specialised the neurone, or excitable nerve cell, making ana­ nature of the constituent cells, with their unique tomical and chemical connections with other function and specificity, is c10sely related to units in the system. Many of the essential bio­ the structure of the whole tissue. The underlying chemical connections of the nerve cell are de­ chemical processes cannot be discussed or seen pendent upon special morphological features: in perspective without constant awareness of synaptic contact is mediated by chemical mol­ related aspects of physiology and morphology. ecules, 'neuro-transmitters' which ensure the The hrain is structurally extraordinarily com­ continued propagation of electrical impulses plex in its distinct anatomical regions, each of through sequential units of the system. Also which is heterogeneous in the types and struc­ c10sely related to the morphology of the ner­ tures of the constituent cells. vous system is the chemical energy expended in One aspect of the biochemical function of maintaining distribution gradients of cations the brain can be seen in its efficient production across cellular membranes. Chemical neuro­ of the energy required to support the unique pro­ transmission results in an alteration in cation cesses referred to above.

Though the major emphasis of this book will be references to several basic texts are given at the to provide the nutritionist with a biochemical end of the introduction. approach to his experimental and practical To facilitate easy reference, the book has problems, it is hoped that the book will also be been divided into chapters according to the of use to the biochemist and physiologist to roles of the basic nutrients in metabolism. demonstrate how dietary nutrition manipula­ Within chapters, discussion will include such tion can be used as a powerful tool in solving topics as the effects of nutrients on metabolism, problems in both physiology and biochemistry. the fate of nutrien ts, the roles of various tissues There will be no attempt to write an all-encom­ and interaction of tissues in utilizing nutrients, passing treatise on the relationship between and the biochernical mechanisms involved. biochemistry and nutrition; rather, it is hoped Toward the end of the book, several example that the suggestions and partial answers offered problems will be presented, which we hope will here will provide the reader with a basis for provide the reader with the opportunity to approaching problems and designing experi­ form testable hypotheses and design experi­ ments.

1. 1 What is Selectivity? purpose, and crop protective agent for the A biologically-active substance is said to be second, but there is no fundamental difference selective if it strongly affects certain cells with­ of principle in their mode of action. out causing any change in others, even when the Drug therapy has two, fundamentally two kinds of cells are close neighbours. In living opposed divisions. The first of these strives to organisms, there are many substances, often improve the action of one of the cell's natural quite small molecules, which have been chosen agents by modifying the molecule in order to for their specificity. This choice has been made localize or intensify its action. For instance, under the strong pressure of natural selection, the solubility can be decreased to make it form unhurried by any consideration of time. Such a deposit, or a change is made so that it becomes chemical compounds operate the metabolism a poorer fit on the naturally-occurring destruc­ of the cells and tissues, and ensure their health, tive enzyme. Both of these devices have proved survival, and reproduction. Important among useful in therapy, e. g. with steroid hormones. the smaller of these selective molecules are Such drugs, which seek to improve on Nature vitamins, coenzymes, hormones, neurotrans­ by performing more desirably, are called mitters, inorganic ions, nutritional fragments, agonists.

entiated free-living organism (larva), which is The success of the Insecta as a class (nearly extensively destroyed and rebuilt into a mor­ 1 million spp.; phylum Arthropoda) is largely phologically different form (adult) suitable for due to their adaptability to profoundly different ecological niches. Insects have attracted the life in a different ecological niche, is controlled attention of scientists both as useful model by a single genome. This is probably the most systems for the study of many basic biological dramatic reorganization of a growing animal phenomena, and also for the rational develop­ known. Certain carefully selected insect ment of new methods of controlling the pest material can, thus, provide suitable model species. As a class, insects have played an systems for developmental studies. important role in the elucidation of numerous The majority of the individual metabolic basic biochemical phenomena. For example, reactions occurring in insects are similar to work on the genetic control of eye pigment those found in other groups of organisms.

46 3. 2 mRNA metabolism 47 3. 3 Initiation complex formation 3. 3. 1 Binding of initiator tRNA 47 3. 3. 2 Binding of messenger RNA 50 3. 4 Elongation 56 3. 5 Termination of protein biosynthesis and post-translational modification 59 RNA phage protein synthesis 61 3. 6 References 63 Index 64 1 Introduction possible control processes operating to adjust 1. 1 The problem protein synthesis to the needs of the cells and The discovery that the genetic material of organism. It will be assumed that the reader has living organisms is DNA, and the later de­ some knowledge of molecular biology in gen­ monstration that the DNA molecule is a eral and protein biosynthesis in particular, but double helix were both great milestones in twentieth century science, and formed the by way of introduction each of the major molecules and stages of the process will be foundation of the new discipline of molecular described in simple terms, and in subsequent biology. But even after these momentous dis­ chapters each will be discussed again in coveries, the detailed mechanism by which such genetic material could be expressed as the struc­ greater depth. tural and catalytic proteins which play so im­ portant a role in the functioning of all living 1. 2 Overall steps in protein biosynthesis The information encoded in the two comple­ cells was still not obvious.

Plants, in addition to their role as primary synthesizers of organic com­ pounds, have evolved as selective accumulators of inorganic nutrients from the earth's crust. This ability to mine the physical environment is restricted to green plants and some microorganisms, other life forms being direct1y or indirect1y dependent on this process for their supply of mineral nutrients. The initial accumulation of ions by plants is of ten spatially separated from the photosynthetic parts, necessitating the transport to these parts of the inorganic solutes thus acquired. The requirement for energy-rich materials by the accumulation process is provided by a transport in the opposite direction of organic solutes from the photosynthetic areas. These transport phenomena in plants have been studied at the cellular level, the tissue level, and the whole plant level. The basic problems of analysing the driving forces and the supply of energy for solute transport remain the same for alI systems, but the method of approach and the type of results obtained vary widely with the experimental material employed, reflecting the variation of the solute transporting properties which have se1ectively evolved in response to both internal and external environmental pressures.

Isoenzymes were 'discovered' 20 years ago and were at first regarded as interesting but rare occurrences. Since then a wealth of information on enzyme heterogeneity has accrued and it now seems likely that at least half of all enzymes exist as isoenzymes. This is important in many areas of biological and medical science. Thus isoenzyme studies have provided the main experimental substance for the neutral drift controversy in genetics and evolution; they have greatly extended our understanding of metabolic regulation not only in animals but also in bacteria and plants; their existence has made available a multitude of highly sensitive markers for the study of differentiation and development, as well as providing indices of aberrant gene expression in carcinogenesis and other pathological processes. Iso­ enzymes are also being used increasingly in diagnostic clinical bio­ chemistry. It is surprising that this phenomenon which affects such a high pro­ portion of enzymes and is clearly important in biochemistry should receive such scant attention in the standard textbooks of that subject, the formal treatment of isoenzymology in these rarely exceeding one or two pages. This may be because the 'pure biochemist' has tended to regard variation in enzyme properties between tissues more as an unwanted complication than as a potential source of insight into diversity of biological function.

Writing this second edition of Biochemical Genetics proved to be more difficult than I had anticipated. The fixed format of the series meant that the addition of new material was made possible only by the dele­ tion of old. Since the book is intended for a student audience, I have retained the historical approach of the first edition and added new material only when it demonstrates a principle more effectively. At the time of writing, we are witnessing an information explosion resulting from the application of recombinant DNA technology to all manner of problems. I have added a sixth chapter indicating the impact of this work on our concepts of gene structure. I should like to thank Ed Byard, Bill Evans, Charles Schorn and Ed Ward, colleagues in the Biology Department at the University of Winnipeg, and Andrew Spence, a student in the department, for their comments on the manuscript of the second edition, and to reiterate my thanks to all those in the Department of Genetics at the University of Sheffield who commented on the first edition.

The student of biological science in his final years as an undergraduate and his first years as a graduate is expected to gain some familiarity with current research at the frontiers of his discipline. New research work is published in a perplexing diversity of publications and is inevitably concerned with the minutiae of the subject. The sheer number of research journals and papers also causes confusion and difficulties of assimilation. Review articles usually presuppose a background know­ ledge of the field and are inevitably rather restricted in scope. There is thus a need for short but authoritative introductions to those areas of modern biological research which are either not dealt with in standard introductory textbooks or are not dealt with in sufficient detail to enable the student to go on from them to read scholarly reviews with profit. This series of books is designed to satisfy this need. The authors have been asked to produce a brief outline of their subject assuming that their readers will have read and remembered much of a standard introductory textbook on biology. This outline then sets out to provide by building on this basis, the conceptual framework within which modern research work is progressing and aims to give the reader an indication of the problems, both conceptual and practical, which must be overcome if progress is to be maintained.

The student of biological science in his final years as an undergraduate and his first years as a graduate is expected to gain some familiarity with current research at the frontiers of his discipline. New research work is published in a perplexing diversity of publications and is inevitably concerned with the minutiae of the subject. The sheer number of research journals and papers also causes confusion and difficulties of assimilation. Review articles usually presuppose a back­ ground knowledge of the field and are inevitably rather restricted in scope. There is thus a need for short but authoritative introductions to those areas of modern biological research which are either not dealt with in standard introductory textbooks or are not dealt with in suffi­ cient detail to enable the student to go on from them to read scholarly reviews with profit. This series of books is designed to satisfy this need. The authors have been asked to produce a brief outline of their subject assuming that their readers will have read and remembered much of a standard introductory textbook on biology. This outline then sets out to provide by building on this basis, the conceptual framework within which modern research work is progressing and aims to give the reader an indication of the problems, both conceptual and practical, which must be overcome if progress is to be maintained.

The student of biological science in his final years as an undergraduate and his first years as a graduate is expected to gain some familiarity with current research at the fron tiers of his discipline. New research work is published in a perplexing diversity of publications and is inevitably concerned with the minutiae of the subject. The sheer number of research journals and papers also causes confusion and difficulties of assimilation. Review articles usually presuppose a background knowledge of the field and are inevitably rather restricted in scope. There is thus a need for short but authoritative introductions to those areas of modern biological research which are either not dealt with in standard introductory text­ books or are not dealt with in sufficient detail to enable the student to go on from them to read scholarly reviews with profit. This series of books is designed to satisfy this need. The authors have been asked to produce abrief outline of their subject assuming that their readers will have read and remembered much of a standard introductory textbook of biology.

The student of biological science in his final years as an undergraduate and his first years as a graduate is expected to gain some familiarity with current research at the frontiers of his discipline. New research work is published in a perplexing diversity of publications and is inevitably concerned with the minutiae of the subject. The sheer number of research journals and papers also causes confusion and difficulties of assimilation. Review articles usually presuppose a background knowledge of the field and are inevitably rather restricted in scope. There is thus a need for short but authoritative introductions to those areas of modern biological research which are either not dealt with in standard introductory textbooks or are not dealt with in sufficient detail to enable the student to go on from them to read scholarly reviews with profit. This series of books is designed to satisfy this need. The authors have been asked to produce a brief outline of their subject assuming that their readers will have read and remembered much of a standard introductory textbook of biology.

1. 1. Aspects of development. usually competent to develop in several differ- If you have been fortunate enough to see a fIlm ent ways. Thus the mesenchyme cells of the of the development of any multicellular organ- embryonic chick limb bud may become, among ism or, better still, to watch live embyros devel- other things, muscle or cartilage cells. Differen- oping, the intricate beauty of the developmental tiation is largely an intracellular process involv- process will not have escaped you: nor will its ing the appearance of cells with certain bio- complexity. Apparent complexity, however, is chemically or cytologically recognizable charac- no reason for despair when one begins to think teristics through the differential activation of in terms of analysing development. Rather, it is genes whose products confer these character- istics on the cello In skeletal muscle cells for astimulus to the first and most important ana- lytical step, that of simplifying the problem by example, specific proteins (actin and myosin) dividing it into aspects which can be meaning- are synthesized, and arranged to give the typical fully studied. striated appearance (Fig. l. la).(Differentiation is the subject of another book in this series, The most obvious way to divide development is on a chronological basis - to begin with ferti- 'Cell Differentiation' by J. M. Ashworth. ) lization and proceed through cleavage, blastu- Recent advances in molecular biology have greatly stimulated research into differentiation lation and gastrulation to organ fromation.

The development of an embryo is one of the which prevents entry of other sperm, fusion of most awe inspiring biological phenomena and the two haploid nuclei occurs and within about the study of cell differentiation can be traced 30 minutes the pigmented cortex rotates with respect to the underlying cytoplasm and in so back in antiquity to Aristotle and beyond However, there are few modern sciences which doing it reveals a grey, crescent shaped area on pay more than a cursory obeisance to their the side of the egg opposite to the point of founders and few students seem very interested entry of the sperm. This is another example of in the theories of their dead predecessors. polarity developing. Soon after fertilization the Embryology, though, is that rare exception - a zygote enters a period of rapid nuclear and cell division. The result of this cleavage process is science where the problems, theories and often that the egg cytoplasm is partitioned between techniques that excite our interest today, are essentially the same as those which excited our numerous cells whose ratio of nuclear volume to cytoplasmic volume is more like that found colleagues of fifty or even a hundred years ago. in an 'average' somatic cell.

1. 1 Historical development of molecular virology of effort on a limited number of phages, Viruses have occupied a central position in notably the Escherichia coli phages T2 and T4. molecular biology ever since its development as At the same time Lwoff and his colleagues were an independent discipline. Indeed, molecular studying phage A, a temperate phage of E. coli, biology itselflargely developed out of the work which was to lead to equally fundamental pioneer studies of Delbriick, Luria and Hershey, observations on the regulation of macro­ who realized, in the late 1930's, that bacterial molecular synthesis. viruses (bacteriophages, often abbreviated to The study of animal and plant viruses has its phages) had properties which made them origins in the latter half of the 19th century uniquely suitable as a model system for an and was largely initiated by workers in medical, attack on one of the then outstanding problems veterinary and agricultural disciplines. Many of of biology, the definition of the gene in their practical successes owe little to molecular physical and chemical terms. The favourable biology, stemming instead from those properties of these viruses include the rapidity approaches successful in combating other of their growth, their ease of assay, and the parasites, such as vector control and the availability of easily scored genetic markers. breeding of resistant varieties of plants.

The brain is the most complex and highly of semi-permeable excitable membranes which specialised of all mammalian organs. Under­ can be caused, rapidly and transiently, to under­ standing the complexity of its function remains go changes in permeability to small chemical man's greatest challenge. The functional unit is molecules and to cations. The highly specialised the neurone, or excitable nerve cell, making ana­ nature of the constituent cells, with their unique tomical and chemical connections with other function and specificity, is c10sely related to units in the system. Many of the essential bio­ the structure of the whole tissue. The underlying chemical connections of the nerve cell are de­ chemical processes cannot be discussed or seen pendent upon special morphological features: in perspective without constant awareness of synaptic contact is mediated by chemical mol­ related aspects of physiology and morphology. ecules, 'neuro-transmitters' which ensure the The hrain is structurally extraordinarily com­ continued propagation of electrical impulses plex in its distinct anatomical regions, each of through sequential units of the system. Also which is heterogeneous in the types and struc­ c10sely related to the morphology of the ner­ tures of the constituent cells. vous system is the chemical energy expended in One aspect of the biochemical function of maintaining distribution gradients of cations the brain can be seen in its efficient production across cellular membranes. Chemical neuro­ of the energy required to support the unique pro­ transmission results in an alteration in cation cesses referred to above.

Though the major emphasis of this book will be references to several basic texts are given at the to provide the nutritionist with a biochemical end of the introduction. approach to his experimental and practical To facilitate easy reference, the book has problems, it is hoped that the book will also be been divided into chapters according to the of use to the biochemist and physiologist to roles of the basic nutrients in metabolism. demonstrate how dietary nutrition manipula­ Within chapters, discussion will include such tion can be used as a powerful tool in solving topics as the effects of nutrients on metabolism, problems in both physiology and biochemistry. the fate of nutrien ts, the roles of various tissues There will be no attempt to write an all-encom­ and interaction of tissues in utilizing nutrients, passing treatise on the relationship between and the biochernical mechanisms involved. biochemistry and nutrition; rather, it is hoped Toward the end of the book, several example that the suggestions and partial answers offered problems will be presented, which we hope will here will provide the reader with a basis for provide the reader with the opportunity to approaching problems and designing experi­ form testable hypotheses and design experi­ ments.

1. 1 What is Selectivity? purpose, and crop protective agent for the A biologically-active substance is said to be second, but there is no fundamental difference selective if it strongly affects certain cells with­ of principle in their mode of action. out causing any change in others, even when the Drug therapy has two, fundamentally two kinds of cells are close neighbours. In living opposed divisions. The first of these strives to organisms, there are many substances, often improve the action of one of the cell's natural quite small molecules, which have been chosen agents by modifying the molecule in order to for their specificity. This choice has been made localize or intensify its action. For instance, under the strong pressure of natural selection, the solubility can be decreased to make it form unhurried by any consideration of time. Such a deposit, or a change is made so that it becomes chemical compounds operate the metabolism a poorer fit on the naturally-occurring destruc­ of the cells and tissues, and ensure their health, tive enzyme. Both of these devices have proved survival, and reproduction. Important among useful in therapy, e. g. with steroid hormones. the smaller of these selective molecules are Such drugs, which seek to improve on Nature vitamins, coenzymes, hormones, neurotrans­ by performing more desirably, are called mitters, inorganic ions, nutritional fragments, agonists.

entiated free-living organism (larva), which is The success of the Insecta as a class (nearly extensively destroyed and rebuilt into a mor­ 1 million spp.; phylum Arthropoda) is largely phologically different form (adult) suitable for due to their adaptability to profoundly different ecological niches. Insects have attracted the life in a different ecological niche, is controlled attention of scientists both as useful model by a single genome. This is probably the most systems for the study of many basic biological dramatic reorganization of a growing animal phenomena, and also for the rational develop­ known. Certain carefully selected insect ment of new methods of controlling the pest material can, thus, provide suitable model species. As a class, insects have played an systems for developmental studies. important role in the elucidation of numerous The majority of the individual metabolic basic biochemical phenomena. For example, reactions occurring in insects are similar to work on the genetic control of eye pigment those found in other groups of organisms.

46 3. 2 mRNA metabolism 47 3. 3 Initiation complex formation 3. 3. 1 Binding of initiator tRNA 47 3. 3. 2 Binding of messenger RNA 50 3. 4 Elongation 56 3. 5 Termination of protein biosynthesis and post-translational modification 59 RNA phage protein synthesis 61 3. 6 References 63 Index 64 1 Introduction possible control processes operating to adjust 1. 1 The problem protein synthesis to the needs of the cells and The discovery that the genetic material of organism. It will be assumed that the reader has living organisms is DNA, and the later de­ some knowledge of molecular biology in gen­ monstration that the DNA molecule is a eral and protein biosynthesis in particular, but double helix were both great milestones in twentieth century science, and formed the by way of introduction each of the major molecules and stages of the process will be foundation of the new discipline of molecular described in simple terms, and in subsequent biology. But even after these momentous dis­ chapters each will be discussed again in coveries, the detailed mechanism by which such genetic material could be expressed as the struc­ greater depth. tural and catalytic proteins which play so im­ portant a role in the functioning of all living 1. 2 Overall steps in protein biosynthesis The information encoded in the two comple­ cells was still not obvious.

Plants, in addition to their role as primary synthesizers of organic com­ pounds, have evolved as selective accumulators of inorganic nutrients from the earth's crust. This ability to mine the physical environment is restricted to green plants and some microorganisms, other life forms being direct1y or indirect1y dependent on this process for their supply of mineral nutrients. The initial accumulation of ions by plants is of ten spatially separated from the photosynthetic parts, necessitating the transport to these parts of the inorganic solutes thus acquired. The requirement for energy-rich materials by the accumulation process is provided by a transport in the opposite direction of organic solutes from the photosynthetic areas. These transport phenomena in plants have been studied at the cellular level, the tissue level, and the whole plant level. The basic problems of analysing the driving forces and the supply of energy for solute transport remain the same for alI systems, but the method of approach and the type of results obtained vary widely with the experimental material employed, reflecting the variation of the solute transporting properties which have se1ectively evolved in response to both internal and external environmental pressures.

Isoenzymes were 'discovered' 20 years ago and were at first regarded as interesting but rare occurrences. Since then a wealth of information on enzyme heterogeneity has accrued and it now seems likely that at least half of all enzymes exist as isoenzymes. This is important in many areas of biological and medical science. Thus isoenzyme studies have provided the main experimental substance for the neutral drift controversy in genetics and evolution; they have greatly extended our understanding of metabolic regulation not only in animals but also in bacteria and plants; their existence has made available a multitude of highly sensitive markers for the study of differentiation and development, as well as providing indices of aberrant gene expression in carcinogenesis and other pathological processes. Iso­ enzymes are also being used increasingly in diagnostic clinical bio­ chemistry. It is surprising that this phenomenon which affects such a high pro­ portion of enzymes and is clearly important in biochemistry should receive such scant attention in the standard textbooks of that subject, the formal treatment of isoenzymology in these rarely exceeding one or two pages. This may be because the 'pure biochemist' has tended to regard variation in enzyme properties between tissues more as an unwanted complication than as a potential source of insight into diversity of biological function.

Writing this second edition of Biochemical Genetics proved to be more difficult than I had anticipated. The fixed format of the series meant that the addition of new material was made possible only by the dele­ tion of old. Since the book is intended for a student audience, I have retained the historical approach of the first edition and added new material only when it demonstrates a principle more effectively. At the time of writing, we are witnessing an information explosion resulting from the application of recombinant DNA technology to all manner of problems. I have added a sixth chapter indicating the impact of this work on our concepts of gene structure. I should like to thank Ed Byard, Bill Evans, Charles Schorn and Ed Ward, colleagues in the Biology Department at the University of Winnipeg, and Andrew Spence, a student in the department, for their comments on the manuscript of the second edition, and to reiterate my thanks to all those in the Department of Genetics at the University of Sheffield who commented on the first edition.

The student of biological science in his final years as an undergraduate and his first years as a graduate is expected to gain some familiarity with current research at the frontiers of his discipline. New research work is published in a perplexing diversity of publications and is inevitably concerned with the minutiae of the subject. The sheer number of research journals and papers also causes confusion and difficulties of assimilation. Review articles usually presuppose a background know­ ledge of the field and are inevitably rather restricted in scope. There is thus a need for short but authoritative introductions to those areas of modern biological research which are either not dealt with in standard introductory textbooks or are not dealt with in sufficient detail to enable the student to go on from them to read scholarly reviews with profit. This series of books is designed to satisfy this need. The authors have been asked to produce a brief outline of their subject assuming that their readers will have read and remembered much of a standard introductory textbook on biology. This outline then sets out to provide by building on this basis, the conceptual framework within which modern research work is progressing and aims to give the reader an indication of the problems, both conceptual and practical, which must be overcome if progress is to be maintained.

The student of biological science in his final years as an undergraduate and his first years as a graduate is expected to gain some familiarity with current research at the frontiers of his discipline. New research work is published in a perplexing diversity of publications and is inevitably concerned with the minutiae of the subject. The sheer number of research journals and papers also causes confusion and difficulties of assimilation. Review articles usually presuppose a back­ ground knowledge of the field and are inevitably rather restricted in scope. There is thus a need for short but authoritative introductions to those areas of modern biological research which are either not dealt with in standard introductory textbooks or are not dealt with in suffi­ cient detail to enable the student to go on from them to read scholarly reviews with profit. This series of books is designed to satisfy this need. The authors have been asked to produce a brief outline of their subject assuming that their readers will have read and remembered much of a standard introductory textbook on biology. This outline then sets out to provide by building on this basis, the conceptual framework within which modern research work is progressing and aims to give the reader an indication of the problems, both conceptual and practical, which must be overcome if progress is to be maintained.

The student of biological science in his final years as an undergraduate and his first years as a graduate is expected to gain some familiarity with current research at the fron tiers of his discipline. New research work is published in a perplexing diversity of publications and is inevitably concerned with the minutiae of the subject. The sheer number of research journals and papers also causes confusion and difficulties of assimilation. Review articles usually presuppose a background knowledge of the field and are inevitably rather restricted in scope. There is thus a need for short but authoritative introductions to those areas of modern biological research which are either not dealt with in standard introductory text­ books or are not dealt with in sufficient detail to enable the student to go on from them to read scholarly reviews with profit. This series of books is designed to satisfy this need. The authors have been asked to produce abrief outline of their subject assuming that their readers will have read and remembered much of a standard introductory textbook of biology.

The student of biological science in his final years as an undergraduate and his first years as a graduate is expected to gain some familiarity with current research at the frontiers of his discipline. New research work is published in a perplexing diversity of publications and is inevitably concerned with the minutiae of the subject. The sheer number of research journals and papers also causes confusion and difficulties of assimilation. Review articles usually presuppose a background knowledge of the field and are inevitably rather restricted in scope. There is thus a need for short but authoritative introductions to those areas of modern biological research which are either not dealt with in standard introductory textbooks or are not dealt with in sufficient detail to enable the student to go on from them to read scholarly reviews with profit. This series of books is designed to satisfy this need. The authors have been asked to produce a brief outline of their subject assuming that their readers will have read and remembered much of a standard introductory textbook of biology.