B O O K REVIEWS

inhabitants of the Earth is unique, and the reason for this lies in our genes. Genes are in chromosomes, and chromosomes, in 23 pairs, are in each of our cells. Unravel a chromosome and you find a 'chemical language in which recipes are written'; this redpe is copied when a protein is needed in the cell, and the 'copy strand' acts as a pattern on which the building blocks of protein are assembled. The uniqueness of the genes in any egg or sperm is assured by pairs of chromosomes swapping their chromosomal arms before eggs and sperm are formed. Girls have chromosome pairs that are all the same size, but boys have an odd pair, and the smaller one of this pair is like an 'upside down Y'. Each of us has two sets of chromosomes, one set from each of our parents, and that is why every one of us is different. Having two copies of every gene means that we can use both or, sometimes, only one. Faulty genes occur when the recipe is mis-copied, this produces 'mutatiom (mew-tay-shons)'. These can be passed on to children by their parents: colour blindness, cystic fibrosis and sickle-<'ell disease are examples. Useful mutations allow living creatures to change and adapt, they create new species and are the molecular events that gave our ape-ancestors legs that can walk upright, less hair and bigger brains, and now the world is filled with five billion unique human mutation products! One can but admire, nay envy, the brevity.

If you have genetically ignorant or uncomprehending relatives this book would perhaps be a good introduction for them. But will R explain to your own children just what you do in the lab all day? How does it stand on its own, as reading material, without a gene.wise mum or dad at hand to help? Fran Baikwill follows a pattern of science education exposition best pioneered by such publishers as Usbome. However, the target readership for this book (age 9--11) will find the technical material and prose density very heavy going indeed, though for this age group the style is right. An older but genetically bewildered teenager (age 15, at GCSE) would follow the content easily, but would fred the childish cartoon style rather patronizing. In its defence, the book seems better taken in context within the series, but the fluctuating levels of difficulty in the text could very easily cause the reader to abandon it. It seems a bit much to expect children so young to see the logic for X- linked defects being so prevalent in boys - there are sixth-formers, aged 17 or 18, who cannot cope readily with that reality.

The book is well designed and lively in its illustration, Complementary coloured bases form the rungs of DNA and even have little speech bubbles amched ('I'm a T and 'I'm an A'). Mic Rolph has used a good range of illus~tive ~les, though I did find, as in his earlier DNA is Here to Stay,

that the drawings do not pomay the DNA molecules as helical - rather, they are built from two overlapping zig-zag ribbons, losing the elegance and flm:~e<limensional nature of Watson and Crick's model and denying one the spatial appreciation that a good drawing elidts. This is a great pity after 40 yeats! It was a nice idea to include the Ishiahara colour-blindness tests, but no comfort for the 'mutants' who get it wrong. The notion of colour blindness is illustrated (to the non-colour blind?) by an illustration of green-faced children with blue hair. Is this a fair impression to leave the 95% with good colour visiorL71 also wonder

how the 10% of boys afflicted will feel about their 'faulty' gene. Couldn't we be told that we each have lots of them?

Education needs the enthusiasm of the specialist geneticist, but sequencing these ideas into a child's intellectual development will require work more careful than this. Nevertheless, the series is a laudable first, and my graduate education students responded to these books with real excitement.

Stephen P. TomHns

Homerton College, Cambridge, OK CB2 2PH.

/ l ~ Search for the transcriptional Holy Grail Gene Transcription: A Practical Approach edited by B. David Haines and Stephen J. Higgim

IRL Press at Oxford University Press, 1993. £25.00 pbk (364 pages) ISBN 0 19 963291 X

Given the current emphasis on understanding gene transcription, practical approaches to its study have wide and important aspirations. As almost all cells of a eukaryotic organism have the same DNA content, many decisions of alternative gene expression must be made to give rise to diverse tissues and functions. Some might argue that gene transcription and its control are at. the root of what cells can do and become and, as regards development, how an organism is made.

Gene D,anscrlption: A Practtcal Approach concentrates on eukaryotic RNA polymerase II and its associated transcription factors, though much of the advice given can be applied to other systems. It is a technique-oriented compilation that sets out to help the reader initiate transcription studies in their own laboratory, rather than to review vast amounts of experimental data. The book should be of great value to both the novice and experienced researcher, and presents a broad variety of methods in one convenient volume. The format of step-by-step protocols makes for easy use, introductory and background comments are included, and the tips and trouble-shooting guides should help the worker obtain meaningful results.

A range of topics is covered, with sufficient cross-referencing to eliminate redundancy among the various chapters. Included are most of the common assays of gene transcription in vitro, such as northern blotting, PCR, S1 and RNase mapping, primer extension and in situ hybridization, though I feel that a protocol for nudear run-on assays could also have been given. One section covers

the study of exogenous genes in mammalian cells - basically, methodology for transient and stable transfection and its applications in studies of gene transcription. Many import,am assays are presented in detail; one example is the ubiquitous CAT assay, which almost everyone seems to have either seen or done. Some of the mutagenesis methods detailed, while very effective, seem somewhat dated. The wide availability of DNA synthesis machines and the recent applications of PCR technology could accomplish many of the mutagenic and manipulative goals outlined, though, of course, whole books are devoted to these techniques and applications alone. The guide to the previousl/daunting task of making active transcriptional extracts from specific tissues (as opposed to less complex ceil- culture sources) is excellent, giving many helpful hints and descriptions of the critical steps in obtaining 'clean' nuclei.

Since one aspect of bioresearch that is impomnt (especially to taxpayers and funding bodies) is its application to medical research, the use of gene therapy to correct defective genes or processes is of particular interest. Understanding and controlling appropriate tissue-specific and temporal expression of genes is also crucial in dissecting developmental decisions. These questions are most directly addressed in a section dealing with the use of transgenic animals (mice) in studies of transcriptional control. Because of the nature and complexly' of setting up and maintaining both mouse colonies and successful tramgenesis strategies, it seems unlikely that a hboratory with no experience of this

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B O O K R E V I E W S

technology could complete the experiments presented without the help of outside expertise and access to appropriate facilities. Nevertheless, the main types of tramgenic expe,'iments and the importance of sound experimental design are outlined, together with the future prospects for such work. Indeed, since this chapter was written at least two labs have succeeded in making transgenic mice carrying large DNA fragments that were cloned in yeast artificial chromosomes, greatly increasing the size of the incorporated transgene, and therefore the potential for achieving 'normal' gene regulation.

Transcription is a central process that responds to various internal and external stimuli; the resultant changes in the profile of gene expression can then complete the cycle, affecting how a cell can respond to its environment. Elements that influence transcription

include enhancers and promoters, binding sites for various protein complexes that can enhance or depress the transcriptional process. Included is a thorough guide to *.he production, isolation and characterization of transcription factors, complementing the experiments with active transcriptional extracts. These procedures have been tried and tested by many workers in many systems, so most will feel confident in using them. A related section gives many protocols currently used to study DNA-protein interactions. A final chapter points out the advantages and applications of heterologous studies in yeast.

An appendix lists known transcription factors and their DNA-binding elements, though this will inevitably fall behind as new elements, systems and genes are studied. In any case, this table is useful to read through and have as a reference.

The list of citations also provides a starting point for further reading in the ninny systems reviewed.

In the study of gene transcription, important questions remain. How do transcription factors actually promote transcription? What mechanisms underlie the distant activity and orientational flexibility of enhancer function? How does chromatin structure affect gene transcription? Gene Transcription: A Practical Approach has collected the most up-to-date methodology, which should shed light on these and other important issues. Experienced researchers and students alike will enjoy this book and find it useful.

Mark Nichols

Gene F2q~ression Programme, EMBL, Mo~hofstrasse I, D-69117 Heidelberg,

Germany.

] ~ A fine and sorry tradition Species Evolution: The Role of Chromosome Change by Max King

Cambridge University Press, 1993. £40.00/$59.95 (xix + 322 pages) ISBN 0 521 353O8 4

Where would the study of evolution be without its shameless squabbles: each blind seer bi'andishing the authorized version of the truth as he gropes at the proverbial elephant? Our ignorance over the proximal causes of species origins, Darwin's 'mystery of mysteries', leads to more rumblings around the poor beast, How did we come to such a pretty pass? Was it the inauspicious start of a bad habit when Huxley slugged it out with Wilbcrforce: evolution driving a pile through the heart of religion and philosophy and feeling nervous over the counterattack ever since? Was it the paucity of evidence leaving the field open to armchair scribblers and fawners waging their personal crusades on behalf of this or that fragment of truth? Or was it the disasterous takeover by mathematical theoreticians who, if they put their minds to it, could wield their esoteric equations and collectively negate the evolvability of every observed phenomenon? Many people in many places have a lot to answer for in turning evolutionary biology into a theological nightmare. What other branch of science would tolerate some of its main provocateurs being largely unable to distinguish the 5' from the 3' end of a gene or the head from the anus of a larva, yet espouse their views on 3.5 billion years of both with the flick of an algorithm or the turn of a clever phrase, ignorance and muddle masquerading behind the pseudo-clarity

of mathematical modelling? ('The intelligent lot, the intuitive lot, the infallible lot we are, we are', G.K. Chesterton, Songs of Education.)

Against this tradition one can hardly grouse about King's pugnacious style as he puts paid to all and sundry who dared argue against the role of chromosomes in speclatlon, With such a tradition, why worry about modem.day subtleties that are beginning to recognize the multiple and intertwined causes of adaptation and speciation as organisms are tossed around on the turbulent seas of the ecology and the genome. Buffered from without and driven from within, there is no single universal process responsible for the illogical tree of life, no general law of biology directing regularities of events where none exist, Of course some chromosomal rearrangements, if and when tLxed by inbreeding or by that rare process of meiotic drive, and ff and when giving rise to 'negative heterotic rearrangements', will lead to reproductive isolation and (perhaps) the inception of biological differentiation. Michael J.D, White said as much in his Modes of Spectatton (Freeman, 1978) as did Barney John in his many writings - two of King's progenitors. But this can hardly be justification - except in the best sorry traditions of the evolution 'debate'- for a tirade against all other spedation mechanisms, with heavy breathing on the side over such trivial matters as the

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(intractable) definition of a species. My old teacher David Harberd told me

that a species is what the familiar expert says it is - a clear recognition that biology is nothing but exceptions. If I had to back a species definition from those dismissed in this book, I would opt for Paterson's 'specific mate recognition system' and Templeton's 'cohesion concept'. They, at least, have the merit of pointing out that species are intrinsically separate functional units because the genetic operations governing species development (right through the haploid-.diploid life cycle) are distinct - yet all individuals of a sexual species are cohesively bound together in such genetic operations through the continual sharing of chromosomes, Such considerations emphasize the positive aspects of differential species ontogenles rather than the negative aspects of 'reproductive isolation' (as embodied in the so-called biological species concept - 'the only valid species concept'), which Darwin himself had difficulties in explaining, with only natural selection at his disposal.

I have never really understood why cytogeneticists fear so many bogies. I spent years as a card-carrying chromosome man but did not see any conceptual contradictions between knowledge gleaned in this field and that gained from my later involvement with the molecular processes of genomes and their evolutionary consequences. Crick wrote of the 1977 Helsinki Chromosome Conference '..,the metaphase chromosome is the dullest form of chromosome. It is not enough, in order to understand the Book of Nature, to turn over the pages looking at the pictures and not reading the text' (Chromosomes Today, pp. 403-407, Elsevier, 1977). I did not fully agree with his lamentation, notwithstanding that he had sat