Life on Planet Earth
BIOLOGY 101
6 February, 1998

- James Watson in The Double Helix

 

1. The central Dogma
2. DNA is like Coke
3. The Family of DNAs
4. A few words about the SIZE of genes.
5. References
 BOOKS on DNA
A Brief History of DNA
Nobel Prizes for work related to genetics/DNA

DNA is the gentic material
The First demonstration of bacterial transformation.
Experiments done by Frederick Griffith (in London) in 1928 found there were two different types of the bacterium Streptococcus pneumoniae:

In 1952, Alfred Hershey and Martha Chase (she was an UNDERGRADUATE at the time!) demonstrated clearly that DNA must be the genetic material, using bacteriophage T2.

RNA -> protein
We will discuss more on the "Central Dogma" on Monday and Wednesday of next week.

2. DNA is like Coke. 

Compare the structures of Caffeine: 

with Adenine: 
Here's the structure of caffeine, flipped:

Caffeine is a "base analogue" of Adenine, and in fact can sometimes be incorporated into a growing DNA chain, instead of Adenine.  Caffeine is a weak mutagen, for this reason.

The VERY MOST important property contributing to DNA helix stability is the stacking of the base-pairs on top of one another, due to hydrophobic forces.  (Remember, the bases "hate" water, and are not very soluble.)  Free bases will stack on top of each other and form a helix in solution!  This type of process is called "self-assembly", where you just throw something in solution, and it fits together on its own, with no extra work needed.
 

 

3. The Family of DNAs

3 families of DNA helices:

A-DNA family - this is most common for double stranded RNA, RNA/DNA hybrids, as well as for certain DNA sequences, such as long stretches of purines.

B-DNA family - DNA exists in the "B-DNA form", most of the time inside the cells of living organisms.  This is the classical "Watson-Crick" structure.

B-DNA

Z-DNA family - this is much more rare than the other two families, although certains sequences (such as runs of GC repeats (GCGCGC)) can form Z-DNA easily.

 

4. A few words about the SIZE of genes & genomes...

• Bacterial genes are often around 1000 bp long.       
  (NOTE: we will talk more about what a gene actually is, on Monday)

• Many human genes are more than 100,000 bp long, and a few (like the gene for muscular dystrophy & cystic fibrosis) are close to 1,000,000 bp long!

 
• The complete GENOME (or all the DNA) from an organism is much generally larger for more complex organisms.  (NOTE, however, that for plants the size can be perhaps 100x to 1000x the size of many animal genomes - this is due to chromosomal duplication, which happens more often in plants than animals.

 
REFERENCES

BOOKS on DNA
 

 1. Sinden, R.R. DNA Structure and Function, (San Diego: Academic Press, 1994).

 

 2. Saenger, W. Principles of Nucleic Acid Structure, (New York, Springer-Verlag, 1984).  A very good, though a bit old, book for the most DETAILED analysis of DNA Structure
 

Some other good textbooks:

* 3. Calladine, C.R. and Drew, H.R. Understanding DNA - The Molecule & How It Works, (San Diego:Academic Press, 1992). (* I like this book!)
 
 

 4. Adams, R.L.P., Knowler, J.T. and Leader, D.P. The Biochemistry of the NUCLEIC ACIDS, (London:Chapman and Hall, 1986, Tenth edition).
 

 5. Blackburn, G.M. and Gait, M.J. Nucleic Acids in Chemistry and Biology, (Oxford:IRL Press at Oxford University Press, 1990).
 

 6. Watson, J., Hopkins, N., Roberts, J., Steitz, J. and Weiner, A. The Structures of DNA. In: Molecular Biology of the Gene, (The Benjamin/Cummings Publishing Company, Inc., 1992).
 

 7. Cantor, C.R. and Schimmel, P.R. Structures of nucleic acids. In: Biophysical Chemistry, Part I, (San Francisco: W.H. Freeman & Co., 1980, p. 155-205).

 some good (less technical) books, written more for people outside the field:

 8. Berg, P. and Singer, M. DEALING WITH GENES - The Language of Heredity, (Mill Valley, California:University Science Books, Blackwell Scientific Publications, 1992).
 

 9. Frank-Kamenetskii, M.D. Unravelling DNA, (Cambridge:VCH Publishers (UK) Ltd., 1993).
 

10. Drlica, K. Understanding DNA and Gene CLONING - A Guide for the Curious, (New York:John Wiley & Sons, 1984).
 

11. Rosenfield, I., Ziff, E. and Van Loon, B. DNA for Beginners, (New York:W.W. Norton and Company, 1983).
 

1865 Gregor Mendel describes "unit of heredity"

1869 Friedreich Miescher isolates "nuclein" (DNA) from trout fish from the Rhine.

1903 Walter Sutton proposes that chromosomes contain genetic material

1908 T.H.Morgan proposes that genes can mutate (somehow), based on work with Drosophila

1927 Muller discovers x-rays induce mutations in chromosomes.

1941 Beadle & Tatum propose "one gene - one enzyme" hypothesis.

1944 Avery, MacLeod, McArty show DNA is "transforming" agent (e.g., genetic material)

1952 Alfred Hershey & Martha Chase demonstrate that DNA contains genetic material

1953 Postulation of complimentary, double helical structure for DNA (by Watson & Crick)
 
1960 Discovery of messenger RNA

1966 Establishment of complete genetic code

1973 Eukaryotic genes cloned in bacterial plasmids

1977 DNA sequencing becomes possible - X174 virus

1984 Human Genome project first started - projected to take 20 years and cost $4,000,000,000.

1993 First clinical trials for gene therapy in humans started in England

1995 First complete bacterial genome sequenced
 
1997 Cloning of "Dolly the sheep"….

A Brief History of DNA

Some  interesting books about the history of DNA:
 

Early 1900’s (1900-1929)

12.  Thomson, J.A., HEREDITY (New York: R.V. Coleman, National Book Buyer's Service, 1907).  This is an interesting view of genetics, BEFORE Mendell’s work had been linked to (Darwinian) evolution, and (of course) long before anybody knew about genes and DNA.

* 13. Morgan, T.H. The Physical Basis of Heredity, (Philadelphia:J.B. Lippincott Company, 1919). In this book, Morgan proposes the idea that perhaps these chromosomes that he observes in Drosophila, might contain the genetic material.  This is the work for which he received the Nobel prize, more than a decade later!

 

1930’s

14. Fisher, R.A., The Genetical Theory of Natural Selection, (Clarendon Press, Oxford, 1930).  This is the first link between Mendellian genetics and Darwinian evolution, even though both of Darwin and Mendell published around the same time (1850’s to 1860’s).  Francois Jacob (1973, see below) makes a strong argument that the two ideas were not really deemed compatible in the late 1800’s, and it was not until the beginning of this century that Mendell’s genes could be considered as a valid mechanism for explaining evolution.

15. Levene, P.A. and Bass, L.W. NUCLEIC ACIDS, (New York:American Chemical Society, 1931). This book was written more than 20 years BEFORE it was known (or even suspected) that DNA contains the genetic material!
 

16. Dobzhansky, Th., Genetics and the Origin of Species  (New York: Morningside Heights: Columbia University Press, 1941).  In this edition, Dobzhansky further links Darwinian evolution to Mendellian genetics (see Fisher (1930), above) - Dobzhansky’s book was important for establishing this idea in the US.

* 17. Schrödinger, E. WHAT IS LIFE & MIND and MATTER, (Cambridge: Cambridge University Press, 1944).  This is the famous book that inspired Crick when he was trying to solve the structure of the DNA helix.  Schrödinger makes some predictions about the nature of the genetic material (at the time thought to be PROTEIN (not DNA!), but his predictions turned out to be very true).  He discusses in detail the hypothesis (of Max Delbrück) that the genetic information might be stored in the form of a "code" - and uses Morse code as an example.  Here are a few quotes:
 "... Consequently, we may safely assert that there is no alternative to the molecular explanation of the hereditary substance..."
 "We shall assume the structure of a gene to be that of a huge molecule, capable only of discontinuous change, which consists in a rearrangement of the atoms and leads to an isomeric molecule.  The rearrangements may affect only a small region of the gene, and a vast number of different rearrangements are possible."
 

* McCarty,M., The Transforming Principle - Discovering that Genes are made of DNA, (New York: W.W.Norton & company, 1985) - Although this book was written more recently, it is an excellent history of the research that was going on in the early 1940's.  I would strongly recommend the reading of this text.
 

18. Pauling,L., The Nature of the Chemical Bond - and the structure of molecules and crystals (New York: Cornell University Press, 1948).
 

1950’s

19. Sinnot, E.W., Dunn, L.C., and Dobzhansky, Th., Principles of GENETICS (New York: McGraw-Hill Book Company, Inc., 1950).

20. Dunn, L.C., Genetics in the 20th Century - Essays of the Progress of Genetics During Its First 50 years (New York: The MacMillan Company,1951).

* 21. Chargaff, E. and Davidson, J.N. The NUCLEIC ACIDS, Volumes 1-3, (New York:Academic Press, Inc., 1955)  This is the "classic" reference work for obscure facts about DNA.  This book was published shortly after the discovery of the structure of the double helix, and before much was known about DNA being the "genetic material".

* 21. McElroy,W.D., Glass,B., (editors)A Symposium on THE CHEMICAL BASIS OF HEREDITY, (Baltimore: The Johns Hopkins Press, 1957).  This is an edited book from a symposium held in 1956, to discuss the recent discoveries of the DNA structure, and that DNA contains the genetic material.  Note that this is still several years before the "genetic code problem" had been solved.  The contributors were at the forefront of research at the time - many of them were later to receive Nobel prizes for their work!

22. Zamenhof, S., The Chemistry of Heredity (Springfield, Illinois, USA: Charles C. Thomas - Publisher, 1959).  This book is written for the "non-scientist", and does a good job of explaining WHY it is important to know about DNA.
 

1960’s

23. Steiner, R.F. and Beers, R.F., POLYNUCLEOTIDES - Natural and Synthetic Nucleic Acids (New York: Elsevier Publishing Company,1961).

24. Davidson, J.N. , The Biochemistry of Nucleic Acids  (New York: John Wiley & Sons, 1965).

* 25. Watson, J.D. Molecular Biology of the Gene, New York:W.A. Benjamin, Inc., 1965. This is the first edition of the "classic" textbook on molecular biology.  At the time it was written, the genetic code was just being completely deciphered.

26.  Phage and The Origins of Molecular Biology , (Cold Spring Harbor, Long Island, New York: Cold Spring Harbor Laboratory of Quantitative Biology, 1966).

* 27. Beadle, G. and Beadle, M., THE LANGUAGE OF LIFE - An Introduction to the Science of Genetics, (Garden City, New York: Doubleday & Company, Inc., 1966).  This is a good overview of genetics, the discovery of DNA, and the "breaking of the [genetic] code".  It was written about 10 years after George Beadle had won the Nobel prize.

* 28. Kendrew, J.C., The Thread of Life - an introduction to molecular biology (Cambridge, Massachusetts: Harvard University Press, 1967).  This is a thin book that gives a good, plain explanation of the "recent discoveries" of the structure of DNA and proteins.  The explanation of how to interpret X-ray diffraction patters is especially nice.

29. Harbers, E., Domagk, G.F., and Müller, W., Introduction to NUCLEIC ACIDS - Chemistry, Biochemistry, and Functions  (New York: Reinhold Book Corporation, 1968).

30. Hayes, W., The Genetics of Bacteria and their Viruses - Studies in Basic Genetics and Molecular Biology  (New York: John Wiley & Sons, Inc., 1968).

*  31. Watson, J.D. The Double Helix, (New York:W.W.Norton & Company, 1968). This is a fun, very readable, "gossipy" account of the discovery of the DNA double helix.  Of course, it is very biased, but nonetheless it makes good reading, and is very insightful into the personalities and politics involved in solving the basic structure of DNA.

32. Bodmer, W.F., Darlington, A.J., Dunn, L.C., Emerson, S., Grell, R.F., Sobell, H.M., and Taylor, J.H., GENETIC ORGANISATION - A Comprehensive Treatise (New York: Academic Press, 1969).
 

*  33. Medvedev, Z.A. The Rise and Fall of T.D. LYSENKO, (New York:Columbia University Press, 1969).  I think this is an important book for several different reasons.  First, it is well-written, and tells a nice story about the history of genetics.  Perhaps more importantly, it also warns of what can happen when the government tries to control scientific thought.  In this particular instance, the government was the Soviet Union, under Stalin.  I am told that the communist Chinese still do not officially believe in Mendellian genetics, and that they must be "careful" when they talk about DNA - many government officials consider this as "bourgeoisie capitalistic ideas".

34. Ycas, M., THE BIOLOGICAL CODE (Frontiers of Biology, volume 12) (Amsterdam: North-Holland Publishing Company, 1969).

1970’s

35. Hershey, A.D., The Bacteriophage Lambda (Cold Spring Harbor, New York: Cold Spring Harbor Laboratory, 1971).

* 36. Jacob, F. The Logic of Life: A History of Heredity, (New York:Vintage Books, 1973).  This is an excellent historical account of the development of the idea of genes (and DNA) as the source of hereditary units.  He traces the history of ideas, in terms of the overall scientific point of view at various times in history.  Basically, Jacob proposes that, although Darwin and Mendell were contemporaries, the time was not right for acceptance of  Mendellian genetics as the form of Darwinian evolution.  He argues that the development of statistical mechanics, and the concept of "negative entropy" (e.g., the universe is running down, or becoming more random, and that it takes energy to prevent things from becoming more disorganised - thus life requires energy to fight the tendency towards decay) were necessary requirements for the acceptance of the "randomness" of the assortment of genes.  Thus he strongly relates developments in the physical sciences to ideas in biology.

37. Lewin, B., GENE EXPRESSION - vol. 2.  Eukaryotic Chromosomes (London: John Wiley & Sons, 1974).

38. Dawkins, R., The Selfish Gene (New York: Oxford University Press, 1976).

39. Grobstein, C., A Double Image of the Double Helix - The Recombinant-DNA debate (San Francisco: W.H.Freeman & Company, 1979).
 

* 40. Judson, H.F. The Eighth Day of Creation - Makers of the Revolution in Biology, (New York:Simon and Schuster, 1979).  This is a comprehensive treatise (686 pages!), detailing the work leading up to, and past the discovery of the double helix.  It is a wonderful historical account of the development of molecular biology, and also is a good source for gaining a basic understanding of the underlying principles of the concepts.  Unfortunately, it is now a bit dated, but still nonetheless a good "starting point".

41. Harsanyi, Z. and Hutton, R., GENETIC PROPHECY: BEYOND THE DOUBLE HELIX (New York: BANTAM BOOKS, 1981).  This book talks about the importance of "genetics" ( = DNA sequence) in determining many aspects of our health and behaviour.  In a sense, because it was written at the early stages of such an explosion in knowledge, this is a good preview of what is happening presently.

42. Watson, J.D. and Tooze, J., THE DNA STORY - A Documentary History of Gene Cloning (San Francisco: W.H. Freeman and Company, 1981).  This is kind of like a "scrapbook", with newspaper clippings, old letters, and lots of interesting stories about the beginning of genetic engineering.

* 43. Gribbin, J. In Search of the Double Helix - Quantum Physics & Life, (New York:McGraw-Hill Book Company, 1985).  This book traces the influence of quantum mechanics on molecular biology.  It is written for the "non-specialist", and offers a different perspective on the history of DNA.  Obviously, this is from a very reductionistic point of view.  While I personally think that you cannot explain ALL of biology from a reductionistic point of view, I do think this approach has been quite successful in many applications - and this book is both an explanation of the approach, as well as a look at its success.

44. Hall, S.S., INVISIBLE FRONTIERS - The Race to Synthesise a Human Gene (Redmond, Washington, USA: Tempus Books of Microsoft Press, 1987).  The "gene" referred to is, (of course) the insulin gene, and this reads a bit like Watson’s gossipy "double helix", but this book is NOT written by one of one of the main characters.

* 45. Crick, F. WHAT MAD PURSUIT - A Personal View of Scientific Discovery, (New York:Basic Books, Inc., 1988).  I used a quote from this book  in the introduction to my thesis:
 "Really the ideas needed to grasp the structure [of the double helix] are, if properly present, ridiculously easy, since they do not violate common sense, as quantum mechanics and relativity do.  I believe that there is a good reason for the simplicity of the nucleic acids.  They probably go back to the origin of life, or very close to it.  At that time mechanisms had to be fairly simple or life could not have started."
 

1990’s

46. Micklos, D.A.,  and Freyer, G.A.,  DNA Science - A First Course in Recombinant DNA Technology (Cold Spring Harbor, New York: Cold Spring Harbor Press, 1990).  This a very good introduction to "molecular biology".  With lots of experimental protocols along with a clear description of the basic principles.  It is presently being used as a supplemental text to our  "Advanced Molecular Genetics" course.

47. Mark Ptashne,  A Genetic Switch - Phage l and Higher Organisms (Oxford: Blackwell Publishers, 1992: 2nd edition).  This is an EXCELLENT text, in terms of "structure function" relationships.  By understanding gene expression and regulation in a very simple "organism" (a small bacteriophage), much insight is given into how DNA functions in animals and plants.
 
48.  Watson,J.D., Gilman,M., Witkowski,J., Zoller,M., Recombinant DNA - A Short Course, (2nd Edition, Published by W H Freeman & Co., 1992; ISBN: 0716722828) This ia very good overview of recombinant DNA technology - written by Jim Watson.  It has managed to withstand the test of time, and is recommended as a good starting point for the "non-specialist".

49.  Lewontin,R.C., Biology As Ideology : The Doctrine of DNA, (Reprint Edition, Published by Harperperennial Library, 1993; ISBN: 0060975199) Lewontin is easily considered one of the world's leading scientists; in this book he examines how "pure science" is in fact shaped and guided by social and political needs and assumptions.   Very interesting reading, although I think he sometimes perhaps goes a bit overboard.

50. Herrmann,B., and Herrmann,S.H., Ancient DNA : Recovery and Analysis of Genetic Material from Paleontological, Archaeological, Museum, Medical, and Forensic Specimens (Heidelberg: Springer Verlag, 1994; ISBN: 0387943080).  Although this does NOT tell you how to reconstruct a dinosaur, it IS a good source of information for many diverse and powerful  applications of recombinant DNA technology.

51.  Primrose,S.B., Old,R.W., Principles of Gene Manipulation : An Introduction to Genetic Engineering (Studies in Microbiology), (Published by Blackwell Science Inc., 1994; ISBN: 0632037121).  This is the 5th Edition of a classic text. As in previous editions, the basic philosophy of this extremely popular text
remains to present the principles and techniques of gene manipulation in sufficient detail for the non-specialist reader to understand them.  This edition has been thoroughly revised, and although it's already a bit outdated, it is still an excellent reference.

52. Dawkins, R., RIVER OUT OF EDEN - A Darwinian View of Life (London: Weidenfeld & Nicolson, 1995).  This book is essentially an updated version of "The Selfish Gene", modified a bit.  Basically the idea is that we (humans) are nothing more than vehicles for replicating our genes, and that "DNA" is our sole reason for existence.  As much as I like DNA, I find this idea philosophically depressing.

53. Eldredge, N., Reinventing Darwin - The Great Evolutionary Debate (London: Weidenfeld and Nicolson, 1995).  This book describes the differences between two different ideas about evolution: the "ultra-Darwinians", including Richard Dawkins (see above) and the "organismal" biologists, who look at the evolution of whole creatures, rather than "just genes".

54.  Mones,P., Stalking Justice; The Dramatic True Story of the Detective Who First Used DNA Testing (Published by Pocket Books, 1995; ISBN: 067170348X).  This is about a serial killer near Richmond, Virginia, who eventually was caught, and the DNA evidence was used to send him to the electric chair in 1994.

55.  Pollack,R., Signs of Life : The Language and Meanings of DNA, (Reprint Edition, Published by Houghton Mifflin Co, 1995; ISBN: 0395735300).  Pollack makes the analogy of DNA sequence being like a "language".  This is a very nice text for an introduction to the conecpt of genetic information being stored in DNA.

56.  Cook-Deegan,R., The Gene Wars: Science, Politics, and the Human Genome (W.W. Norton & Company, New York, 1996).  I reviewed this book for Bios magazine, and also used this review as a topic for a Religion & Philosophy Colloquium Disscussion in December of 1997.  Click on the picture of the book for a link to the web page for the review.

57.  Nelkin,D., Lindee,M.S.,  The DNA Mystique : The Gene As a Cultural Icon (W H Freeman &Co., 1996; ISBN: 0716730499)  This book was written by two sociologists.  I thought some of their points were interesting, but I was a bit dissapointed with their lack of understanding of the science.  Perhaps it really is a better discussion of what SOCIETY at large thinks of DNA, rather than what is the mindset within the scientific community.

58.  Soyfer,V.N., Potaman,V.N., Triple Helical Nucleic Acids, (Published by Springer Verlag, 1996; ISBN: 0387944958) This is an exhaustive reference about triple-stranded DNA.  It is quite technical, but very useful for people in the field!

59.  Levy, H., And the Blood Cried Out : A Prosecutor's Spellbinding Account of DNA's Power to Free or Convict, (Reprint Edition, Mass Market Paperback, Published by Avon press, 1997; ISBN: 0380730618)
 

60.  Teichler-Zallen, D.,  Does It Run in the Family? : A Consumer's Guide to DNA Testing for Genetic Disorders, (Published by Rutgers Univ. Press, 1997; ISBN: 0813524466).  Genetic testing is becoming ever more common, with many more difficult choices as more tests tell us more about ourselves.

61.  Primrose, S.B., Principles of Genome Analysis : A Guide to Mapping and Sequencing DNA from Different Organisms, (2nd Edition, Published by Blackwell Science Inc., 1998; ISBN: 0632049839).  There are already several Universities that offer a course in "comparative genomics" - an area that was not even possible a mere two years ago!  This is a good source book for what will surely become an important field in the new future - the comparison of complete DNA genomes.
 

Nobel Prizes for work related to genetics/DNA

In today's New York Times:

• Study Ties Folate, B-6 to Reduced Heart Disease.


• Study Places HIV Origins a Decade Earlier.


• Fossils From China Are Earliest Known Animals.

Last modified on: 3 February, 2000 by Dave Ussery