What is DNA and What Does it Do?
February 23, 2004
Readings: Starr, Ch 3: p 46, Ch 12 p 190-191, 194-195; CD-ROM: great animations of DNA! (*If you would like to read a pretty interesting synopsis of the race to solve the structure of the DNA double helix, read this story about Watson and Crick.)
Remember: Warm Up 6 and Good For 6 due this week!
It has not escaped our notice that the specific pairing that we have postulated immediately suggests a possible copying mechanism for the genetic material". -- Nobel Laureates James Watson and Francis Crick, after solving the structure of DNA in 1953
I. The not-so-exciting discovery of DNA..from (ewww) open wounds:
In 1868, Johann Friedrich Mieschner, a physician, was collecting the fluid draining from patients' wounds after injury or surgery. He eventually purified a chemical from the white blood cells and pus oozing from these wounds (yuk!). He noticed that this chemical was acidic, contained a lot of phosphate and nitrogen, and was localized to the cell's nucleus. He called this chemical nuclein, and eventually, it became known by a more precise name: deoxyribonucleic acid, or DNA.
Who would have thought that these humble beginnings would eventually result in our knowledge of genetics, cell division, inheritance, and protein synthesis!
II. Nucleic Acids: the 4
monomers:
The monomer for all nucleic acids is the
nucleotide, which has 3 parts:
Chargaff's Rule: A scientific finding that did not seem significant at first, but was eventually a crucial piece of information to understanding the structure of the DNA double helix. In 1947, Erwin Chargaff detemined that the ratio of nucleotide monomers (A, C, G, T) in DNA was always the same in a given organism:
However, Chargaff did not realize the significance of this finding as it relates to the structure of DNA - which was not to be determined for another 6 years (and not by Chargaff, either!)
II. The Nobel Prize-winning Discovery of DNA as the Genetic Material
In the early 1900s it was discovered that chromosomes controlled heredity (more on this later)
Most
scientists thought proteins were the hereditary material -
their R groups are diverse and have numerous interesting
chemical properties. Nucleic acids like DNA seemed too
uniform to be able to account for the thousands of traits of an
organism - no one could imagine how DNA could carry genetic
information - chemically it seemed like a really boring
molecule.
However, several key experiments provided evidence that DNA is the genetic material:
Finally, after this and several other key experiments, there was acceptance that DNA was in fact, the genetic material. The race was on to solve the puzzle - how could DNA transmit genetic information? What was the 3-dimentional structure of DNA?
III. The really exciting, and Nobel Prize-winning, discovery that DNA is a Double Helix:
The race:
between Linus Pauling,
Rosalind Franklin and Maurice Wilkins, and James Watson
and Francis Crick
Although all of these scientists were working fast
and furious to solve the structure of DNA, Watson and Crick (1953)
were the first to propose the correct model, which was
corraborated by Franklin and Wilkins.
Watson and Crick proposed that DNA is a double helix, and built a model based on what was known about the structure of DNA from X-ray crystallography (done by Rosalind Franklin and Maurice Wilkins) and the experiments mentioned above (Hershey and Chase, Chargaff, and others).
At first, they weren't sure where to put the bases (Inside the helix? Outside the helix?) until they remembered Chargaff's rule. (A = T, C= G). This arrangement fit perfectly! Thus, wherever one molecule has an A, the opposite strand has a T, and a G in one strand is always paired with a C = complementary base pairing. This was a VERY significant finding about DNA - the order of bases on one DNA strand determines the order of bases on the other...
Watson and Crick submitted a one-page paper to the journal Nature. They ended the paper with this (not so) subtle statement:
"It has not escaped our notice that the specific pairing that we have postulated immediately suggests a possible copying mechanism for the genetic material".
Shortly after that (1962) they bought their tickets to Stockholm!! Maurice Wilkins was also given the Nobel Prize (Why didn't Rosalind Franklin receive the Nobel Prize?).
Interested in reading more about this classic Race to the Finish, filled with drama, intrique, chauvinist remarks, and the discovery of DNA?
14 April 2003: Press Release: The Human Genome Project is finished BETHESDA, Md., – "The International Human Genome Sequencing Consortium, led in the United States by the National Human Genome Research Institute (NHGRI) and the Department of Energy (DOE), today announced the successful completion of the Human Genome Project more than two years ahead of schedule. 'The Human Genome Project has been an amazing adventure into ourselves, to understand our own DNA instruction book, the shared inheritance of all humankind,' said NHGRI Director Francis S. Collins, M.D., Ph.D., leader of the Human Genome Project since 1993. "All of the project’s goals have been completed successfully – well in advance of the original deadline and for a cost substantially less than the original estimates."
25 April 2003: Happy Birthday Double Helix! It's DNA Day! On April 25, 1953, James Watson and Francis Crick published their landmark letter to Nature describing the DNA double helix. Nature marked the 50th anniversary of the event with a free Nature web focus "containing news, features and web specials celebrating the historical, scientific and cultural impacts of the discovery of the double helix." To find out more, see The National Human Genome Research Institute (NHGRI)
IV. What is the Structure of DNA, the Macromolecule ?
DNA is a nucleic acid - a polymer - that contains
multiple copies of the 4
nucleotide monomers - Adenine (A),
Cytosine (C), Guanine (G), and Thymine (T) arranged in a spiral
staircase shape - the DNA double helix.
The nucleotides, when joined together, polymerize to form a long strand, the backbone of which is repeating sugar and phosphate groups that twist around each other to form a double helix "staircase".
The backbone, or "stair rails" consists of repeating nucleotides joined sugar-to-phosphate - a sugar-phosphate backbone
The nitrogenous bases, "rungs", are held together by weak hydrogen bonds between the A and T and the C and G base pairs:
The
structure of the DNA
Double Helix.
Note the "sugar-phosphate backbone" (red ribbons) and
the "rungs" made up of the blue bases A, C, G and T
How much DNA is in a human cell? Every cell in your body (only exception: mature red blood cells!) has a nucleus packed with DNA, tightly coiled and condensed around histone proteins to make it all fit in. If stretched out, it would be about 1 meter long! From just one cell! (And you have 75 trillion cells!!)
Each cell contains the complete 'genome' of an organism, and in our case contains 3 billion (3,000,000,000) A, C, G, and T' base pairs!!! In each cell! (And you have 75 trillion cells!!) Different genes (pieces of DNA) are turned on or off in cells to give each cell type its specific properties (ie: liver cell, heart cell, brain cell). The human genome contains ~30,000 genes, which can be made into ~100,000 different proteins.
Biological Unity of DNA: All living organisms use the same 4 nucleotide bases of DNA (or a related molecule, RNA) as the genetic material, and use the same machinery (ribosomes) to turn the information in DNA and RNA into protein. DNA from different organisms can be joined or 'spliced' together and introduced into a cell, and this recombinant DNA is treated just like any other DNA in the cell - it is copied and made into protein in whatever cell it is put into. This is the basis of the Biotechnology industry - read this week's Good For about Humulin, recombinant DNA Human Insulin made in bacterial cells!
The Genes We Share: This cool chart compares how similar we are to other experimental "model organisms" that scientists like to work with because of there usefulness as 'lab rats' (so to speak!) in discovering similarities in disease and developmental processes in humans - specifically mice, fruitfiles, roundworms, and yeast - all eukaryotes. Read the entire booklet here.
V. What does DNA DO?
1. DNA makes copies of itself (DNA replication) DNA replication precedes cell division. Before cells divide in two (mitosis) the DNA within the cell must make an identical copy of itself so that each of the two cells receives a complete copy of DNA. We will talk about this after Exam 1 when we talk about mitosis, or cell division!
2. DNA encodes information (for protein synthesis) DNA segments called genes encode directions to make proteins that control cellular growth and metabolism. (Transcription and translation, later in the semester).
3. DNA controls cells and tells them what to do (by gene expression) DNA contains regulatory elements to turn genes on or off in tissues or at different times in development (Later in the semester).
4. DNA changes by mutation: DNA is the molecule of heredity, and contains genetic information and genetic changes (mutations) that are passed on to offspring. (Genetics, later in the semester).
Learning Objectives:
1. Explain the 4 important functions of
DNA as the molecule of heredity
2. Summarize experiments performed by the
following scientists, which provided evidence that DNA is the
genetic material:
3. Describe the structure of DNA with
regard to the sugar phosphate backbone and the nucleotide bases.
What is Chargaff's rule?
4. What is a 'genome'? What is a 'gene'?
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