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The discreet charm of molecular evolution

Approches MolCculaires de 1’Evolution by Jacques Ninio, Masson, Paris, New York, Barcelona and Milan, 1979. (132 pages) ISBN 2 225 62623 5

The origin of life and the evolution of living cells are certainly amongst the most intrigu- ing problems in molecular biology, for which a general understanding at the molecular level is a central aim of current research.

It is the purpose of this book by Jacques Ninio to review, in a critical but very con- structive way, the various .approaches and main conclusions that have been reached in this extensive field; the book, however, is not merely a description and summary of our current understanding, but rather an interesting and thoughtful discussion of the most basic aspects of the molecular proces- ses or strategies that may be used by the cell in order to evolve. In this, Jacques Ninio does not hesitate to question fundamental concepts in molecular biology, or evolutionists who think that a detailed comparison between amino acid or nucleic acid sequences of a few selected macro- molecules may provide the key to our understanding of how the cell has evolved. The same may be said of comparisons of functions.

For Jacques Ninio, the essential problem in molecular evolution is to consider how the living cell has evolved from a simple, but nevertheless coherent system at a primitive stage, to another coherent but more elaborate system that we now find. One aspect of this process in which he is most personally interested and involved, is related to the gradual acquisition and refinement of the specificity with which dif- ferent components of the cell interact with each other, and the related but often neg- lected aspect of this development: the progressive elimination of undesirable interactions in the cell.

Besides the intrinsic capacities of macromolecules for specific recognition, Jacques Ninio elaborates and discusses several strategies that are used or might be used by cells in order to ameliorate the levels of accuracy attainable in simple rec- ognition processes, or to adapt the specific- ity of recognition to multiple and perhaps varying evolutionary constraints. In any such process of adaptation the cell is oblivious to its potential destiny and attempts a piecemeal assembly of the gene- tic apparatus (as others now do ‘genetic engineering’) in answer to the challenges of

evolution; the system of immune defense in eukaryotic cells is amongst the most strik- ing illustrations of such cellular strategies at the genetic level.

Each chapter examines a different aspect of molecular evolution: those concerned with aquisitive evolution, the stability of the genetic code and prebiotic evolution displaying perhaps the greatest degree of originality. In this book we have moved a long way from comparisons between molecules at the level of their chemical constitution, the usual diet for discussions between molecular evolutionists;

The language used by the author is sim- ple yet adequate, little encumbered by unnecessary technicalities or mathematical formulation. Important ideas are often illustrated by ingenious models that really assist communication of the concepts involved. At the end of the book an excel- lent general as well as specialized biblio- graphy is provided for each chapter.

Incorporated in this book are a number of observations that do not strictly concern molecular evolution but rather scientific politics or relations between scientists, which are not necessarily all they might be. It is indeed undeniable that criticism of cur- rent modes of scientific thinking is some- times stifled simply because the established view emanates from eminent personalities. The ‘evolution of scientific knowledge’ depends to some extent on these problems and there is some justification for alluding to them. Our only criticism of this book is that some such remarks emerge in a very personal way which will inevitably offend

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some members of the scientific community. We are afraid that some will attempt to dis- credit the real scientific value of this book on account of the few indiscretions which it contains; this would be unfortunate.

In conclusion, this book is small in size (132 pages) but remarkably rich in ideas. It deseives to be read not only by specialists in the field but by anyone who wishes to gain access to the more exciting aspects of molecular evolution.

HENRI GROSJEAN RICHARD BUCKINGHAM

Henri Grosjean is ai the Department of Molecular Biology, University of Brussels, Belgium. Richard Buckingham is at the Institute of Physicochem- ical Biology, Paris, France.

Unravelling the cell’s surface Cell Surface Glycoproteins: Structure, Biosynthesis and Function, Volume 11 of ‘Current Topics in Membranes and Transport’

edited by R. L. Juliano and Aser Rothstein, Academic Press, London and New York, 1978. f16.90 (518 pages) ISBN 12 153 3026

With the shift of emphasis in biology from molecular to cellular aspects, there has been a remarkable increase of interest in cell membranes, and in particular in mem- brane carbohydrates. In animal cells, car- bohydrates comprise a small proportion (l-10%) of the weight of the surface mem- brane, and they are attached either to pro- teins or to lipids, forming glycoproteini or glycolipids, respectively. The oligosac- charide units of these glycoproteins and

glycolipids are structurally diverse, and they are all located on the outer surface of the cell. This strategic location enables them to serve as sensitive antennae with which the cell may probe its environment. By virtue of their structural variability, they are admirably suited to function as specific- ity markers. Indeed, it has been known for some 30 years that sialic acid, a prominent cell surface sugar, acts as the receptor for the influenza virus. Recently, it has been shown that other cell surface saccharides act as receptors for bacteria (e.g. for Escherichia coli and Salmonella typhi), glycoprotein hormones (thyrotropin and human chorionic gonadotropin), certain bacterial toxins (cholera and tetanus) and for interferon. There is also a growing body of evidence suggesting that cell surface sugars are of crucial importance in intercel-

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lular communication, in regulation of cell growth and differentiation and in the immune response. Moreover, characteris- tic changes occur in cell surface sugars dur- ing malignant transformation, as has been demonstrated with the aid of lectins.

The appearance of a new book on cell surface glycoproteins is, therefore, a wel- come event to the many scientists interested in this topic. Coming only two years after the publication of ‘Membrane Glycoproteins’ by R. C. Hughes it also attests to the vitality of the research on the subject.

The new book is a collection of nine review articles, all written by specialists and active researchers in the topics with which they deal. However, as is often the case with multi-author books, the quality is not uniform throughout.

The opening article by A. Rothstein is particularly interesting and instructive, since it presents a brief (13 pages) and very readable account of the history of mem- brane research and of the current state of the art. It is followed by an article on the structure and biosynthesis of membrane glycoproteins by J. Sturgess, M. Moscarello and H. Schachter. The discussion of struc- ture is somewhat cursory and dwells almost exclusively on soluble glycoproteins, since the number of membrane glycoproteins that have been isolated in a form pure enough for structural studies is very small, perhaps a dozen or so. In fact, the first definitive carbohydrate structure of a membrane glycoprotein, that of the vesicu- lar stomatitis virus, was published only last year. It is in agreement with the assumption presented also by Sturgess et al. in their article, ‘that the oligosaccharide moieties of membrane-bound glycoproteins are structurally similar to the moieties present on secretory glycoproteins’.

Biosynthesis is dealt with in detail, including the formation of sugar nucleo- tides and lipid-linked intermediates, the assembly of N-glycosidically linked car- bohydrate units, and the properties of glycosyltransferases - several of which have now been purified to a high degree. A clear scheme illustrating the biosynthesis of a membrane glycoprotein and its insertion into the plasma membrane is presented. It is based on the recent exciting work on the biosynthesis of viral membrane glycopro- teins, which has demonstrated that attach- ment of N-glycosidic carbohydrate units occurs on nascent chains, inside the vesicles of the endoplasmic reticulum, in the course of translation, and that subsequent modifi- cation of the carbohydrate units occurs in the Golgi apparatus.

In the following article, R. L. Juliano

presents a very useful survey of techniques for the analysis of membrane glycopro- teins. Methods for the specific labeling of surface glycoproteins (e.g. the widely used galactose oxidase-sodium borohydride technique) for the isolation of the labeled membranes and for fractionation of their constituents, are critically discussed, pre- cautions are mentioned and pitfalls pointed out. Special emphasis is given to lectin affinity techniques, which are proving to be of enormous value in the isolation and characterization of membrane glycopro- teins. The survey of methods for the determination of the carbohydrate struc- ture of glycoprotein is, however, weak and in part outdated.

Membrane enzymes which are glycopro- teins are dealt with at length in the article by J. R. Riordan and G. G. Forstner. Some 20 such enzymes have been well character- ized, most of which are bound to the brush border membranes of intestinal and renal proximal tubular cells. They include glycosyltransferases, cytochrome bs reduc- tase, acetylcholinesterase, and various other hydrolases. The authors make the point that glycoprotein enzymes are an important part of cell membranes con- tributing to both their structure and func- tion. The nature of the association of the enzymes with the membrane, whether electrostatic or hydrophobic, is discussed, as is the possible function of the carbo- hydrate, which is still obscure.

Studies of enveloped viruses are making decisive contributions to our knowledge of membrane glycoproteins. This is because of the similarity of viral envelopes to those of other biological membranes, their rela- tive simplicity and in particular the fact that some of them, like vesicular stomatitis virus, contain only one glycoprotein. R. W. Compans and M. C. Kemp discuss these enveloped viruses, with special attention to their organization and biosynthesis, as well as the assembly of viral membrane - a sim- ple and excellent model for the assembly of other membranes.

M. J. A. Tanner, deals with erythrocyte glycoproteins. The human erythrocyte membrane is probably the most intensively studied cell membrane. Its major sialo- glycoprotein, glycophorin, is the best- characterized membrane glycoprotein. However, even for this molecule the struc- tures of the carbohydrate units (1.5 of the 0-glycosidic type, and one N-glycosidic) have not yet been fully elucidated and they are still based on the pioneering work carried out in the 1960s by the late R. J. Winzler and his co-workers. Although glycophorin serves as the paradigm for membrane glycoproteins, there are indica-

tions that this may be unjustified. Other well-studied membrane glycoproteins, such as ‘Band 3’ (the human erythrocyte anion channel), appear to differ from glycophorin in their structure, their disposi- tion within the membrane and function.

The importance of cell surface glycopro- teins and proteoglycans as mediators of cell-to-cell and cell-to-substrate adhesion is discussed in the article by L. A. Culp. There are good reasons to believe that the specificity of these interactions is analog- ous to that of enzyme-substrate, anti- gen-polysaccharide, and lectin-carbohy- drate interactions. The article is too long for the amount of solid evidence available on the subject, and the treatment is some- what unbalanced. Too much space is allo- cated to work from the author’s own laboratory on a cell-surface adhesion com- plex that remains firmly adherent to the substrate on which animal cells were grown. Also, the article is difficult to read because of the excessive use of uncommon abbreviations and the occasional use of very long and complicated sentences (one on p. 382 is 91 words long!)

The article by K. D. Noonan is mainly an attempt to summarize the many conflicting reports and theories on the effect of pro- teolytic modification of cell surface mac- romolecules in stimulating cell growth. It reads like a series of accounts on the ‘rise and fall of . . .‘. In my opinion, the book should have contained no more than an abridged and carefully edited version of this article. In some of the figures the legends are incomplete and the style is very heavy.

The last article, by M. Letarte, again makes refreshing reading. It deals in a clear and balanced manner with glycoprotein antigens of murine lymphocytes, the most important of which are the H-2 antigens. Much is known about the genetics and immunology of these and some of the other antigens discussed (such as the Ia anti- gens). Unfortunately, the small amounts of starting material and the lack of micro- techniques for isolation and structural analysis of the products, have greatly ham- pered their chemical characterization. Here, as elsewhere in the book, it is very clear that development of new techniques, especially micromethods, is the key to further progress.

There is a certain amount of unnecessary overlap between the different articles. For example, the dubious role of cell surface glycosyltransferases as mediators of inter- cellular adhesion, is discussed at length both by Riordan and Forstner, and by Culp. As noted in both articles, even the presence of such enzymes on cell surfaces

TIBS - September 1979

has not yet been unequivocally demon- strated.

The various articles were completed by the end of 1976, and most of them updated in 1977. The book does not include, there- fore, some of the recent significant developments in the study of membrane glycoproteins, such as the processing or trimming of N-glycosidically-linked car- bohydrate units or the demonstration that the polypeptide sequence of glycophorin, and not its carbohydrate structure, is responsible for differences between blood group M and N activity.

The book is produced at the high stan- dard characteristic of Academic Press and is illustrated by schemes, graphs and elec- tron micrographs. There are relatively few typographic errors, although there is indis- criminate and sometimes non-uniform use of symbols and abbreviations. The reader would have benefited not only if the number of abbreviations had kept to an essential minimum, but also by the inclu- sion of a list of the abbreviations (and

acronyms) used. The index is unfortunately much too short with less than 500 entries; at least twice as many entries should have been given.

It is a pity that the book comes under the major title ‘Current Topics in Membranes and Transport 11’ (as is printed on the spine); because of this, it may be over- looked by many potential readers.

On the whole this is a very useful book. At the price of $39.50 it is also a good buy. With the current explosive rise in interest in membranes on the one hand, and in glycoproteins on the other, most of it should be read and re-read by those re- searchers who are fascinated by the cell surface, and who believe that in unravelling its structure and function, particularly that of its glycoproteins, they will find answers to some of the central problems of biology - those of growth, differentiation and malignancy.

NATHAN SHARON

N. Sharon is at the Department of Biophysics, Weiz- mann Institute of Science, Rehovot, Israel.

The seeds of the evolutionary tree are sown The Beagle Record - Selections from the original pictorial records and written accounts of the voyage of H.M.S. Beagle edited by Richard Darwin Keynes, Cam- bridge University Press, Cambridge, New York and Melbourne, 1979. f30 (xiv + 409 pages) ISBN 0 52121822 5

‘I find to my great surprise that a ship is sin- gularly comfortable for all sorts of work. Everything is so close at hand, & being cramped makes one so methodical, in the end I have been a gainer. . . . I think, if I can so soon judge, I shall be able to do some original work inNatural History. . . .’

Thus, in prophetic. innocence, wrote Charles Darwin to his father at the outset of the round-the-world voyage that indeed did determine his brilliant career as a naturalist. During five years exploration of South American and Pacific coasts, the recent university graduate, intending clergyman, and emissary of Cambridge’s prestigious scientific professors, developed a profound vocation for science and accumulated the evidence for his life’s work. Darwin’s crucial formative voyage of personal discovery vividly comes to life in his letters to his family, friends and mentor Professor Henslow, and in the extracts from his diary included in this attractive volume edited by his great-grandson, Richard Darwin Keynes. Informal writings such as these are unsurpassed for the immediacy and color of Darwin’s fist impressions, for example, of walking in a Brazilian rain forest.

‘The delight one experiences in such times bewilders the mind; if the eye attempts to follow the flight of a gaudy butter-fly, it is arrested by some strange tree or fruit; if watching an insect one forgets it in the strange flower it is crawling over; if turning to admire the splendour of the scenery, the individual character of the foreground fixes the attention. The mind is a chaos of delight, out of which a world of future & more quiet pleasure will arise.’

But as Dr. Keynes’ wide-ranging selec- tion of original documents, watercolors and drawings, and early published accounts illustrates, Darwin was not voyaging through strange seas of thought alone. On the contrary, his endeavors - like those of the several participants who are re- presented in The Beagle Record - were shaped and supported within the larger context of the British Admiralty’s hydro- graphical program. It was Captain Francis Beaufort, appointed Hydrographer in 1829, who devised and directed the work of this second BeagZe voyage under Captain FitzRoy. At a time of renewed British con- cern for an expanding world trade and empire, Beaufort’s efforts were not only suitably ambitious (over 170 major survey- ing expeditions were sent out during his 25year tenure), but also scientific on an unprecedented scale. The Hydrographer shared the interests of his Cambridge scien- tist friends Herschel, Whewell, Babbage, Peacock, Airy, Lubbock and incorporated parts of their research programs in astronomy, meteorology, terrestrial mag- netism, the tides, and. geology into his

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instructions to FitzRoy. Not least, Beaufort recruited from the ranks of their students one Charles Darwin, in answer to Fitz- Roy’s request for a gentleman companion cum naturalist.

In The Beagle Record we reap the rewards of Beaufort’s judicious planning and of the sheer competency and ingenuity of his agents on the seas. The master-work of the book is the reproduction of 54 watercolors and drawings, produced in part at Beaufort’s behest, by the ship’s artist Conrad Martens. Martens’ exquisite views of harbors, towns and landscapes, and of scenes of Beagle life, appear at appropriate intervals in the Beagle’s progress around the world, enthralling the reader in a writ- ten narrative interesting enough in its own right. It is the great achievement of the editor to have at last brought to light these valuable but long neglected pictorial records.

Among the less well known artifacts of Captain FitzRoy’s command are his pro- gress reports to the Beaufort, some of which are hitherto unpublished. His assessment of one of the crew puts our knowledge in wider perspective. ‘Mr Dar- win is a very superior young man, and the very best (as far as I can judge) that could have been selected for the task.’ The naturalist’s growing collection of speci- mens, he noted, ‘is numerous and valuable, and will convince the Cantabrigians that their envoy is no Idler.’ In extracts from his own published, though long out of print, Narrative, we follow FitzRoy in some of his most interesting ventures on behalf of the British Empire - installing a missionary at Tierra de1 Fuego, then withdrawing him under threat of violence; disciplining Queen Pomare of Tahiti for confiscations from British ships; and setting up floats, weights and pulleys among the Keeling Islands to investigate geologist Charles Lyell’s theory of the formation of coral reefs.

Much of the Darwin material is already familiar from the vast literature. Neverthe- less, in the setting of a narrative retelling the Beagle’s historic mission through sev- eral points of view, Darwin’s remarks often illuminate anew the growth of his own intellectual horizons. In a letter to his col- lege friend, former entomological compan- ion and cousin William Darwin Fox, he records the enthusiasm the voyage has given him for yet another branch of sci- ence. In geology, Darwin apprises Fox,

‘there is so much larger a field for thought than in the other branches of Natural His- tory. I am become a zealous disciple of Mr Lyell’s views, as known in his admirable book. Geologising in South America, I am tempted to carry parts to a greater extent