Chapter 10: DNA and the Molecular Structure of Chromosomes
Section One of Two Sections on Chapter 10 (Link to Section 2)
- In 1868, J.F. Miescher isolated DNA from pussy bandages.
- The acid contained both phosphorus and nitrogen, unusual for acids.
- This acid, coined nuclein, later was found to be the genetic information molecule, DNA.
Functions of Genetic Material:
- must store information and replicate with high fidelity to account for the accurate transmission of information from parent cells to daughter cells and from parents to offspring;
- must be able to be used to control development and the maintenance of the phenotype of the organism;
- must be changeable, slowly and naturally, over time to accommodate species' adaptability over the eons, (must mutate);
- must be consistent with the then existing evidence which was that the transmitted heritable information was contained in the chromosomes;
- chromosomes are composed of two types of macromolecules: protein and nucleic acid; therefore, the heritable information molecule had to be one or the other.
- At first it was guessed that the genetic information molecule was the protein. This was because the alphabet of amino acids is far greater than that for nucleic acids, 20 versus just 4, respectively.
- However, it was proved that the genetic information was in fact the nucleic acid.
The Proof that DNA is the Molecule of Heredity
- DNA, not RNA, is the predominant nucleic acid found in chromosomes.
- Griffith, 1928, conducted experiments with Diplococcus pneumoniae strains.
- One strain was virulent (Type S) and the other not (Type R). (Figure 9.1)
- The interesting thing was that dead Type S could change living Type T, causing it to become a virulent strain. Dead changing the living! This meant genetic information did not have to be "alive". Also, the substance of heredity was contained somewhere in the debris of the dead cells.
- Genetics text writers commonly criticized Griffith unfairly for having dropped the ball at this point of the investigation.
- It was not until 1944 that Avery, MacLeod and McCarthy continued the experiment to prove DNA was the "transforming factor". (Figure 9.1)
- Why was it so long before Griffith's experiment was completed? Because technology and knowledge walk hand in hand down the path of progress. New techniques were available to these scientists.
- Using Griffith's experiment as the starting point, Avery et al. degraded various fractions of the cellular debris of the dead Type S bacteria and found that only when the DNA was degraded was there a loss in the transforming ability. (Figure 9.2)
- Additional experiments further supported that DNA is the genetic material.
- T2 phage experiment by Hershey and Chase demonstrated with a limited confidence that DNA was the genetic material of a T2 bacteriophage. (Figure 9.3)
- A few exceptions were found where the genetic material of some types of viruses is RNA, not DNA. (All autonomous organisms, including all prokaryotic and eukaryotic organisms, use DNA for their genetic information storage molecule.)
- Fraenkel-Conrat and coworkers first discovered that RNA was the genetic molecule for the tobacco mosaic virus (TMV).
- They separated the protein and RNA of the virus and used both separately to try to infect plant cells.
- They mixed the protein from one strain with the RNA of another to reconstitute infectious particles.
- The RNA not the protein determined the kind of protein that was made by the replicating virus. See Figure 9.4.
- DNA macromolecules are composed of nucleotide subunits.
- Each is composed of a phosphate group, a five-carbon sugar, and a cyclic nitrogen-containing compound called the base. See Figure 9.5.
- There are just 4 kinds of bases found in DNA or in RNA.
- For DNA: adenine (A), guanine (G; name derived from the Spanish word for bird excrement), thymine (T) and cytosine (C).
- RNA has all but thymine is not found; uracil is the equivalent base for it.
- A and G are purines, double-ringed bases.
- C and T are pyrimidines, single-ringed bases.
- RNA is found single-stranded in the cell.
- DNA is found double-stranded in the cell.
DNA Structure: The Double Helix
- Chargaff's rule: The amount of A base found in the DNA of a cell equals T and the amount of C found in a cell equals the amount of G.
- This discovery provided an important clue as to the structure of the double-stranded DNA molecule.
- Clues also came in the form of X-ray diffraction patterns.
- James Watson and Francis Crick used these clues and information from a chemist about the normal form of DNA found in conditions like those of a living cell, what is called tautomeric structure, plus cardboard, to model the structure of the DNA.
- Watson later wrote what many other scientists called a highly controversial book, but what you and I might call a light hearted account, titled "The Double Helix", which described the process of his discovery .
- It's short and fun reading; I highly recommend you read it.
- There is an argument that other scientists would have determined the structure of DNA if Watson and Crick hadn't.
- Certainly, someone would have eventually. However, I think they had what it takes. They were unaffected by their ignorance and therefore sought advice where ever they could find it.
- Their major competitor was secretive and cloistered.
- The structure proposed was that of a double stranded molecule in the shape of a helix, that turned to the right, had a major and minor groove, was antiparallel, and had A forming two hydrogen bonds with T, and had C forming three hydrogen bonds with G. See Figure 9.12.
- Therefor a purine is always associated with a pyrimidine. With this structure the backbone of the molecule, which is made of sugar-phosphate-sugar-phosphate repeats, would sweep evenly, without going in and out, toward or away from the center of the molecule.
- Their model was perfect in every way. Even the distances were predicted with precision.
- Today, we're still predominantly using the original proposed model in genetics discussions. It was a defining accomplishment in scientific and world history.
- A nucleoside is the chemical name of the sugar and the base, but minus the phosphate. If the term nucleoside is used and there is one or more phosphates bonded, then you must describe the phosphates separately; for example, deoxiadenosine monophosphate. See Figure 9.6.
- A nucleotide is a sugar and base with one or more phosphate groups. It fails to be descriptive about the number of phosphates.
- In Figure 9.6, nucleotide is used as the slide title, because each of the molecules has a phosphate.
- The names below each are the name of it as a nucleoside because the phosphate is being described separately, in this case, as a monophosphate.
- We can also use symbols: dGMP, dCMP, dTMP, and dAMP; are the abbreviated symbols for the nucleoside monophosphates or nucleotides.
- The molecules of DNA monomers are not symmetrical.
- I commonly state that they have a 5' head and a 3' tail.
- We will learn later that in nature, during DNA replication, a head is always snapped onto a tail of an existing polymer. See Figure 9.7.
- For now, it's important for you to notice the head and tail of the DNA monomer.
- For each strand of a double-stranded DNA molecule in the direction of 5' to 3' there is another one that complements it that is going in the opposite direction: 3' to 5'.
- Whenever you find a C on one strand, you find a G across it on the other, and vice versa.
- Whenever you find a T on one strand you find an A on the other, and vice versa.
- The two strands are held together by the accumulated strength of otherwise weak hydrogen bonds. See Figure 9.6.
- Be sure to review your general biology text if you do not clearly recall the nature of hydrogen bonds.
- There are three hydrogen bonds formed between each C/G pair, and two between each A/T pair. See Figure 9.11.
- Heat will "break" these bonds. Which type do you think are more stable at elevated temperature?
- Eastern's DNA art gallery, which you can connect to from the other links page, has many models of DNA molecules made by the person who writes molecule modeling programs. Take a look: The DNA Art Gallery
DNA Structures: Alternate Forms of Double Helix
- The Watson-Crick model is DNA in the B-form.
- This is the most predominant form found of DNA.
- Also found are A and Z forms. See Figure 9.13.
- A form does not exist within a cell but DNA-RNA double-strands and RNA-RNA double-strands can take on a similar structure.
- Z-DNA, a zigzag-like structure, can be found in regions of DNA that are G:C rich.
- It has twelve bases, instead of 10 bases, per turn.
- DNA in prokaryotes is a long single continuous circular molecule.
- A special class of enzymes can cut this molecule and twist it so it has another level of coiling. See Figure 9.15.
- Supercoils would not occur globally in organisms that have linear DNA molecules, like those found in us.
- On a regional scale it does, and is necessary for DNA replication, and most likely, gene regulation, RNA transcription and genetic recombination.
- The enzymes that make supercoils are called topoisomerases.
- Gyrase is an example, and has been isolated from prokaryotes and eukaryotes.
Ribo & Deoxiribo-nucleosides Problem Set
Link to Section 2
Dr. Herr's Biology 171 relevant chapter notes for foundational information
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