Preface

Basic and essential topics suitable for courses on nucleic acids for graduate students are scattered throughout the literature, and as devotees can attest, the subject remains in transition and continues to expand in new directions. At the front lines of research the subject is necessarily treated under the heading of different disciplines, often in journals that are not readily accessible. I have attempted to include discussions of as many disparate topics as possible together under the same cover, and in a format that minimizes the distractions of methodologies while including important interdisciplinary and analytical topics and explanations. Of necessity some discussions are superficial. 

The stress is on the chemistry and biology of the nucleic acids, with a consideration of proteins as informational biopolymers in order to call attention to their associated biosynthesis and roles with the nucleic acids in gene expression, replication and maintenance, but also in recognition of the complement nature of their interactions and co-evolutionary origins. Monographs and texts on nucleic acids generally lack a suitable treatment of proteins that would give better appreciation of their interaction with nucleic acids. Proteins are required in one capacity or another for virtually all molecular processes, and are the principle products of living organisms. The minimal treatment of the proteins here is not designed as a substitute for excellent texts on proteins.[i]^{, [ii],[iii],[iv]} 

The goal has been to convey as complete a picture as possible of the nucleic acids and proteins, their structures, biological properties, origins and evolution at a level suitable for graduate and upper-level undergraduate students. Though it is somewhat incidental to the chemical origins and evolution of the nucleic acids, the underlying picture is one of the unity of life, of which man is a part. Brief discussions, footnotes and boxed asides touch on analytical and physical topics, and only at an introductory level appropriate for upper level biology students, and in such a way that hopefully leads to further exploration, or that complements descriptive material in introductory texts in molecular and cellular biology. Methodologies and physical properties of the nucleic acids and proteins have been covered more thoroughly and in commendable style by Cantor and Schimmel, [v] Bloomfield, et al,[vi]^,[vii] and Saenger.[viii] Although it is far from a complete list, other texts useful in studies of the informational biopolymers include those by Adams, et al,[ix] Alberts, et al,[x] Berry, et al,[xi] Chang,[xii] Chang,[xiii] Eigen,[xiv] Friedberg, et al,[xv] Lewin,[xvi] Miller, et al,[xvii] Purves, et al,[xviii] and Mathews and van Holde.[xix] These or comparable texts are prerequisites for the subjects discussed in this volume, and I recommend that students have access to them. 

This volume contains more material than can be covered in the usual one-semester course, since it is designed to meet three requirements: to provide a clear and incisive treatment of nucleic acids at a level accessible to students in all fields of the biological sciences, to provide topics and questions for students coming into the course with specialized backgrounds and interests, and to provide topics together with original citations as a basis for student writing experiences. Although problems are included, the material covered is rich in unarticulated questions that advanced and serious students of the subject should be readily able to identify. 

The broad spectrum of topics relating to the nucleic acids is a good basis for the practice students need in writing, since it allows them to indulge their interests in an array of topics not necessarily covered in class. For this reason I have included citations that oftentimes represent different perspectives on specific topics using different methods of analysis. Besides recognizing the pioneers, the older references are often easier to read where they lack the specialized and abbreviated vocabulary that characterizes much of contemporary literature. The extensive bibliographies that follow each chapter are therefore mainly for the benefit of students in their research and writing requirements. The experience of writing 5, 6 or 10 papers/semester-course is not sufficient, of course, for students to become proficient in recognizing important questions, organizing their thoughts and mastering the craft at a level required for the submission of acceptable manuscripts, but it is at least a contribution. 

If the emphasis of the course is to be on the chemistry of the informational biopolymers, the core chapters are 1-4, plus the first half of 5, all of 6, first three-quarters of 7, and all of 8 and 9. A number of sections and topics can be expanded with material cited or abridged or omitted if deemed unsuitable to a particular group of students without breaking the flow of argument. If the emphasis is to be on the molecular biology of the informational biopolymers, the core chapters are 1, 3-7, 9-12. The format of the book is also suitable for specific discussion and special topics courses for students and instructors with particular interests. Thus, molecular evolution can be covered with selected sections of the core chapters, together with Chapters 7, 10-13, while a course on the origin of life can be presented with the core chapters together with Chapters 7, 11 and 13. A special topics course on protein-nucleic acid interactions can be assembled from material in Chapters 3, 5, 9, 10, and 12. 

Over the years the majority of students who enrolled in my courses were from the biological sciences, but it was not unusual to find a significant number of students from physics, chemistry, the computer sciences and engineering, and in this regard I suspect that my experience is not unusual. While these students often lack some of the prerequisites expected of students of biology, they are more proficient in areas that students of biology are often not exposed to, bringing skills in physics and physical chemistry that have been most responsible for our understanding of biology at the molecular level. It is important to these students that they find biological phenomena discussed in a way they can quickly appreciate and readily explore. It is, of course, no less important for students of the biological sciences for the detailed explanations of molecular phenomena. 

I have had the encouragement and assistance of many colleagues, but I make special mention of my closest longtime collaborator and son Jon. Despite an extraordinarily active academic career, Jon has always accepted my calls for help and comment on matters of science and computers. A more knowledgeable, effective and patient teacher is unimaginable. He has maintained my computers, introduced me to the Linux operating system, and installed and coached me in the use of the molecular modeling program Molscript,[xx]^,[xxi] which together with Raster3D[xxii]^,[xxiii] has been used to display many of the molecular structures in this book from coordinates in the Protein Data Bank (PDB) at the Research Collaboratory for Structural Bioinformatics (RCSB),[xxiv] or in the Nucleic Acid Database (NDB).[xxv] Besides several well known unix-based modeling programs running on Sun and SGI machines, the vector postscript outputs of NUCPLOT[xxvi] and RASMOL[xxvii] have been particularly useful. I recommend that students acquire a good quality adjustable 3D viewer for viewing the many stereo images in this book. Not everyone has that easy ability to separate what each eye is seeing, taught to me by an old colleague of mine who makes his living primarily in the area of molecular graphics.  

I owe a special debt of gratitude to J. R. Fresco and S. D. Delcourt for many wonderful years of collegial discussions of science and for their expert advice and encouragement when I needed it. Thanks also to R. Cochrane for her help in collating many thousands of references from my collection of the early literature. The following read sections of the book, which were returned with excellent comments and suggestions: N. L. Allinger, R. F. Doolittle, R. Chang, J. R. Fresco, G. F. Joyce, W. K. Olson, L. E. Orgel, K. E. van Holde, J. Völker, and P. H. von Hippel. They have my sincere thanks. Thanks also to members of the Chemistry Department and Schow Science Library at Williams College and the Science Library at SUNY Albany for their kind hospitality. 

R.D.B.
University of Maine

End notes

[i] Schulz, G.E. and Schirmer, R.H. (1979) Principles of Protein Structure. Springer-Verlag: New York.
[ii] Lesk, A.M. (1991) Protein Architecture, A Practical Approach. IRL: New York.
[iii] Branden, C. and Tooze, J. (1991) Introduction to Protein Structure. Garland: New York.
[iv] Creighton, T.E. (1993) Proteins: Structures and Molecular Properties. Freeman: New York.
[v] Cantor, C.R. and Schimmel, P.R. (1980) Biophysical Chemistry Part I: The Conformation of Biological Macromolecules; Part II: Techniques for the study of Biological Structure and Function. Part III: The Behavior of Biological Macromolecules. Freeman: New York
[vi] Bloomfield, V.A., Crothers, D.M. and Tinoco, I., Jr. (1974) Physical Chemistry of Nucleic Acids. Harper & Row: New York.
[vii] Bloomfield, V.A., Crothers, D.M., Tinoco, I., Jr., and Hearst, J. (2000) Nucleic Acids: Structures, Properties, and Functions. University Science Books: Sausalito, CA.
[viii] Saenger, W. (1984) Principles of Nucleic Acid Structure. Springer-Verlag: New York.
[ix] Adams, R.L.P., Knowler, J.T., and Leader, D.P. (1992) The Biochemistry of the Nucleic AcidsI. 11^th Edition. Chapman and Hall: London.
[x] Alberts, B., Bray, D., Lewis, J., et al. (1994) Molecular Biology of the Cell, 3^rd Edition. Garland Publishers: New York, pp 921–934.
[xi] Berry, R.S., Rice, S.A. and Ross, J. (1980) Physical Chemistry. John Wiley & Sons: New York.
[xii] Chang, R. (2000) Physical Chemistry for the Chemical and Biological Sciences. University Science Books: Sausalito, CA.
[xiii] Chang, R. (2001) Chemistry. 7^th Edition. McGraw-Hill: New York
[xiv] Eigen, M. and Winkler-Oswatitsch, R. (1996) Steps Toward Life. Oxford University Press: New York.
[xv] Friedberg, E.C., Walker, G.C. and Siede, W. (1995) DNA Repair and Mutagenesis. ASM Press: Washington, D.C.
[xvi] Lewin, B. (1999) Genes VII. Oxford University Press: New York.
[xvii] Griffiths, A.J.F., Miller, J.H., Suzuki, D.T., Lewontin, R.C., and Gelbart, W.M. (1999) An Introduction to Genetic Analysis. 7^th Edition. Freeman: New York.
[xviii] Purves, W.K., Sadava, D., and Heller, H.C. (2001) Life: The Science of Biology. 6^th Edition. Sinauer: Sunderland, MA.
[xix] Mathews, C.K. and van Holde, K.E. (1995) Biochemistry 2^ond Edition. Benjamin/Cummings: New York.
[xx] Kraulis, P.J. (1991) MOLSCRIPT: A program to produce both detailed and schematic plots of protein structures. J. Appl. Crystallogr. 24, 946-950.
[xxi] Esnouf, R.M. (1997) An extensively modified version of MOLSCRIPT  that includes greatly enhanced coloring capabilities. J. Mol. Graphics 15, 132-134.
[xxii] Merritt, E.A. and Murphy, M.E.P. (1994) Raster3D Version 2.0 – A program for photorealistic molecular graphics. Acta Cryst. D50, 869-873.
[xxiii] Merritt, E.A. and Bacon, D.J. (1997) Raster3D: photorealistic molecular graphics. Meth. Enzym. 277, 505-525.
[xxiv] http://www.rcsb.org
[xxv] Berman, H.M., Olson, W.K., Beveridge, D.L., et al. (1992) The nucleic acid database: a comprehensive relational database of three-dimensional structures of nucleic acids. Biophys. J. 63, 751-759; http//beta-ndb.rutgers.edu.
[xxvi] L Pratt, Biochemistry Department, University of Maine.
[xxvii] R. Sayle, Biomolecular Structures Group, Glaxo Wellcome Research & Development, Stevenage, UK.