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.
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],
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
Berry, et al,[xi]
Friedberg, et al,[xv]
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]
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
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
University of Maine
[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. 11th Edition. Chapman and Hall: London.
Alberts, B., Bray, D., Lewis, J., et
al. (1994) Molecular Biology of the Cell, 3rd 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. 7th 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. 7th Edition. Freeman: New York.
[xviii] Purves, W.K., Sadava, D., and Heller, H.C. (2001) Life: The Science of Biology. 6th Edition. Sinauer: Sunderland, MA.
[xix] Mathews, C.K. and van Holde, K.E. (1995) Biochemistry 2ond 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.
[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.