The Central Dogma: From DNA to Proteins February 23, 2000
Revised 2 / 25 / 00
The Central Dogma: From DNA to Proteins
February 23, 2000
Revised 2 / 25 / 00
Readings: Starr text: Ch 13 front page, 13.1 - 13.5
"A threefold cord is not quickly broken."
--Ecclesiastes iv. 12.
Outline I. From DNA to Protein - the Central Dogma |
I. From DNA to Protein - the central dogma.
DNA is a huge information database that carries the complete set of instructions for making all the proteins a cell will ever need!
Although there are only four different bases in DNA (A, C, G and T), the order in which the bases occur determines the information to make a protein, just like letters of the alphabet combine to form words and sentences:
Compare: RAT - TAR - ART - same 3 letters; completely different meanings.
The DNA in each chromosome can be divided into portions known as genes.
Q: What are genes? A: Genes are "working units" of DNA.
Generally, each gene "codes for" (contains the instructions for) one protein.
- This is sometimes called the "one-gene, one-protein" hypothesis.
Every gene is made up of thousands of nucleotides (A, C, G, and T). Each human cell contains ~100,000 genes, coding (potentially) for ~100,000 proteins.
- However, only a small percent of genes are used in any given cell type - "liver" genes, "heart" genes, etc., making a liver cell cell very different from a heart cell. A normal cell activates just the genes it needs at the moment and actively suppresses the rest.
Draw a gene on a chromosome :
Q: If DNA is in the nucleus and proteins are synthesized in the cytoplasm, on ribosomes, how to they "get together"?
A: The answer: use a "messenger" to carry the instructions out into the cytoplasm. A nucleic acid very similar to DNA, called mRNA or messenger RNA, serves this function the "bridge" between DNA and protein:
II. What is RNA and where does it come from?
DNA can not only serve as a template for making copies of itself (more DNA), it can also "unzip" and be used as a template for making RNA
Two big differences between DNA and RNA: (see Figure 13.2 and 13.3)
1. The sugar in DNA is deoxyribose; in RNA it is ribose
2. The nitrogenous base uracil (U) is used in RNA in place of T (they are very similar bases; in RNA U= A just like T = A.)
The RNA molecule that is sent into the cytoplasm is basically just a copy of one particular gene; RNA carries instructions to make whatever proteins the cell needs at that particular time. It is also a single stranded molecule, not a double helix.
III. Transcription = Re-writing DNA into RNA (Figure 13.4)
During transcription, the "messenger", mRNA, complementary to a gene on DNA is made in the nucleus. DNA is "transcribed" or re-written into RNA in three steps (see Fig 12.4):
Steps of transcription:
1. Initiation: A region called a "promoter" in front of a gene gets a signal from the cell that more copies of that gene's protein are needed...fast! A short stretch of the DNA double helix starts to unwind at the start of a gene.
2. Elongation: RNA polymerase makes a copy of just that one the gene. Many copies of mRNA are made while the DNA helix is in this unwound state.
3. Termination: RNA polymerase hits the transcription "stop" sequence AATAAA and the mRNA is completed
4. Processing: "Finishing touches" added to process the mRNA (see Fig 13.5):
a. A "cap" and a "tail" (AAAAAA...) are added to the ends of the mRNA to protect transcripts from digestion and to help the mRNA exit nucleus.
b. RNA splicing: the mRNA transcript is cut apart to remove unneeded pieces. Regions called "exons" are kept, and regions called "introns" are discarded.
The exons are rejoined or "spliced", and the transcript leaves the nucleus to get translated (Phil Sharp and Richard Roberts - 1977 Nobel Prize).
IV. What's the connection between mRNA and protein? (Figure 13.6)
The order of the bases in the DNA specifies the order of bases in the mRNA, and
The order of bases in the mRNA specifies the order of amino acids in a protein.
The genetic code is a triplet code (handout) (Figure 13.7)
- 1. Nucleotide bases on mRNA are read "three at a time" by the ribosome.
- Every three nucleotides in an mRNA specifies the addition of one amino acid in a protein.
- Each three-letter "word" (combination of nucleotides) is called a codon. Therefore, amino acids are coded by a series of three-letter "words" - a 300 nucleotide mRNA will code for a 100 amino acid protein.
2. The amino acids corresponding to all 64 codons have been determined - this was done in the 1960s by Marshall Nirenberg and others (Nobel Prize!)
- All proteins start with the initiation codon AUG (Met)
- All proteins end with stop codons -either UAA, UGA, or UAG
- Some codons that differ in the third nucleotide can still code for the same amino acid - this is called "wobble".
All living organisms and viruses use this triplet genetic code - its that "biological unity" idea again!!!
Objectives for 2/23 and 3/1:
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