BIOL 1400 -- Lecture Outline 22

BIOL 1400 -- Lecture Outline 22

"If you go buzzing about between right and wrong, vibrating and fluctuating, you come out nowhere; but if you are absolutely and thoroughly and persistently wrong, you must, some of these days, have the extreme good fortune of knocking your head against a fact, and that sets you all straight again." -- Thomas Henry Huxley

I. Recap:

DNA base pairs are arranged in a particular order.
1. That order carries meaning -- just as the order of letters in this sentence carries meaning.
2. Specifically, each gene is a stretch of DNA that carries the instructions that you need to make one protein.
3. Here's the DNA base sequence that carries the instructions for making the protein insulin, which regulates the amount of sugar in your blood.
  
  TTGTATTGGGGGTTTTGGCTGTTACTCTGTCTCTCCATCAGGTCATCATCCTTTCATCATG GCTCTGTGGATGCATCTCCTCACCGTGCTGGCCCTGCTGGCCCTCTGGGGGCCCAACACTA ATCAGGCCTTTGTCAGCCGGCATCTGTGCGGCTCCAACTTAGTGGAGACATTGTATTCAGT GTGTCAGGATGATGGCTTCTTCTATATACCCAAGGACCGTCGGGAGCTAGAGGACCCACAG GGTGAGCCCCTACCTGCCATCCCTGCTGTTTCCGTGCCAGTACCCCAGCTGGCAGGGCATA AGTAAGCAGGAAGCTAATTCCAAGGAGAGTCGATGGGTTTGTTGAAAAGGGAGGCGGCTCT CTTGGTCATTTCGTAAAGTGGTGGTGGCTTCCTATAGCTGCTTTTAAGGGTAAAGGGTAAC AGCTGCACCCTTCAGCTGTGGCTTCTGAGCACAACTGGACTCTTCCCTCCACTTGCCTTCG AATGACTGCCCTGGCCTCATGGCAACAGTAGCTCCCTGGTACCAATTTTATTATGCAGATT GCATCTTGGTGTTGATAGCCTTAGGGTAGCCTGGGGGCCATTCATGGGGCGCCCCATCCCT CCTTCCTCCCTGCCTCTGGACAAATGCTCCATGGAGCTCCAAGCTCTGCCACGTGGGAGGT GTGGGTCTCCAGCGCTCTGTGTGCCCAGCATGGCAGCCTCTGTCACCTGGACCAGCTCCCT GGGAGATGCAGTGAGAGGGTGGTAGTGTGGGGCCAGTGCGCAGGCATTCTGCTGCTCCTGA CAGCATCTGCCCCTGTCTCTCTCCCCACTGCTGCTGCTCCTGTATTCTGGCACCTCACCCT GCAGTGGAGCAGACAGAACTGGGCATGGGCCTGGGGGCAGGTGGACTACAGCCCTTGGCAC TGGAGATGGCACTACAGAAGCGTGGCATTGTGGATCAGTGCTGTACTGGCACCTGCACACG CCACCAGCTGCAGAGCTACTGCAACTAGACACCTGCCTTGAACCTGGCCTCCCACTCTCCC CTGGCAACCAATAAACCCCTTGAATGAGCCCCATTGAATGGTCTGTGTGTCATGGAGGGGG AGGGGCTGACTCAAGGGGGCACATGCATGCCAGCCTATCATCCAGGTTCATTGCAAGACCC CCTCTCTATGCTCTGTGCACCTCTAACACACCC
  
  Whew!

II. But how do you get from DNA to protein?

See, here's the problem:
1. DNA (in eukaryotes, anyway) is never found outside the nucleus.
2. Yet proteins were known to be made in the cytoplasm, not in the nucleus.
Francis Crick came up with what he called the "adaptor hypothesis": There must be some molecule that acts as a "go-between", or "adaptor", between the DNA and the protein sequence.
1. We now know that the "adaptor" is a molecule of the other important nucleic acid -- RNA.
  1. RNA is similar to DNA, but differs from DNA in several ways:
    - it's usually single-stranded and doesn't form a double helix
    - the sugar in its nucleotides is ribose, not deoxyribose
    - instead of using the base thymine, it uses a different base called uracil (abbreviated U.)
  2. You can see the differences in these formulas:
    
    Left: deoxyribose bonded to thymine. Right: ribose bonded to uracil.
The Central Dogma of Molecular Biology is this: Information is copied and transmitted in only one direction:

DNA -> RNA -> protein
(There are exceptions to the rule, but for now, understanding the Central Dogma will work. . . )

III. Transcription

Transcription is the first step in the Central Dogma scheme: Information is copied from DNA to RNA
1. A DNA sequence is used as a pattern to make a single strand of RNA which is complementary to it.
  1. Here we have two strands of DNA that would form one double helix:
    
    ATGGCTCTGTGGATGCATCTCCTCACCGTG -- complementary strand
    TACCGAGACACCTACGTAGAGGAGTGGCAC -- template strand
    
    Enzymes unzip the helix. Then the enzyme RNA polymerase make an RNA strand that is complementary to the template strand:
    
    AUGGCUCUGUGGAUGCAUCUCCUCACCGUG -- messenger RNA strand
    TACCGAGACACCTACGTAGAGGAGTGGCAC -- template strand
    
    This RNA -- called messenger RNA -- peels off the DNA. Here's the messenger RNA, or mRNA, for insulin. . .
    UUGUAUUGGGGGUUUUGGCUGUUACUCUGUCUCUCCAUCAGGUCAUCAUCCUUUCAUCAUG GCUCUGUGGAUGCAUCUCCUCACCGUGCUGGCCCUGCUGGCCCUCUGGGGGCCCAACACUA AUCAGGCCUUUGUCAGCCGGCAUCUGUGCGGCUCCAACUUAGUGGAGACAUUGUAUUCAGU GUGUCAGGAUGAUGGCUUCUUCUAUAUACCCAAGGACCGUCGGGAGCUAGAGGACCCACAG GGUGAGCCCCUACCUGCCAUCCCUGCUGUUUCCGUGCCAGUACCCCAGCUGGCAGGGCAUA AGUAAGCAGGAAGCUAAUUCCAAGGAGAGUCGAUGGGUUUGUUGAAAAGGGAGGCGGCUCU CUUGGUCAUUUCGUAAAGUGGUGGUGGCUUCCUAUAGCUGCUUUUAAGGGUAAAGGGUAAC AGCUGCACCCUUCAGCUGUGGCUUCUGAGCACAACUGGACUCUUCCCUCCACUUGCCUUCG AAUGACUGCCCUGGCCUCAUGGCAACAGUAGCUCCCUGGUACCAAUUUUAUUAUGCAGAUU GCAUCUUGGUGUUGAUAGCCUUAGGGUAGCCUGGGGGCCAUUCAUGGGGCGCCCCAUCCCU CCUUCCUCCCUGCCUCUGGACAAAUGCUCCAUGGAGCUCCAAGCUCUGCCACGUGGGAGGU GUGGGUCUCCAGCGCUCUGUGUGCCCAGCAUGGCAGCCUCUGUCACCUGGACCAGCUCCCU GGGAGAUGCAGUGAGAGGGUGGUAGUGUGGGGCCAGUGCGCAGGCAUUCUGCUGCUCCUGA CAGCAUCUGCCCCUGUCUCUCUCCCCACUGCUGCUGCUCCUGUAUUCUGGCACCUCACCCU GCAGUGGAGCAGACAGAACUGGGCAUGGGCCUGGGGGCAGGUGGACUACAGCCCUUGGCAC UGGAGAUGGCACUACAGAAGCGUGGCAUUGUGGAUCAGUGCUGUACUGGCACCUGCACACG CCACCAGCUGCAGAGCUACUGCAACUAGACACCUGCCUUGAACCUGGCCUCCCACUCUCCC CUGGCAACCAAUAAACCCCUUGAAUGAGCCCCAUUGAAUGGUCUGUGUGUCAUGGAGGGGG AGGGGCUGACUCAAGGGGGCACAUGCAUGCCAGCCUAUCAUCCAGGUUCAUUGCAAGACCC CCUCUCUAUGCUCUGUGCACCUCUAACACACCC

IV. Translation

The messenger RNA goes out to a specialized organelle in the cytoplasm called a ribosome. It's the ribosome that "reads" the messenger RNA and translates it into a sequence of amino acids.

But how are you supposed to read this?
1. Get the idea? A cell can read this string of DNA bases:
  
  . . . AUGGCUCUGUGGAUGCAUCUCCUCACCGUG . . . .
  
  and get this string of amino acids, the primary structure of insulin:
  
  methionine - alanine - leucine - tryptophan - methionine - histidine - leucine - leucine - serine - valine - . . .
2. Notice that the code is redundant -- one amino acid may be coded by several triplets. (There are sixty-four possible triplet codons and only twenty amino acids, so this is bound to happen.) For instance, in the example above, both CUG and CUC code for the amino acid leucine. (So do the codons CUU, CUC, UUA, and UUC, by the way.)
3. Finally, three DNA codons don't code for any amino acid, but instead mean "stop stringing amino acids together." (These three stop codons are UAA, UAG, and UGA.)

V. How's translation happen?

Again: translation happens on ribosomes. . .
. . . with the help of other types of RNA molecules called transfer RNAs.
1. There are sixty-four different types of transfer RNA molecule. They're all single- stranded, but the strand loops back on itself at several points.
2. Each tRNA molecule has one loop (called the anticodon loop), that has three bases that stick out. These can form hydrogen bonds with a complementary mRNA codon.
3. Each tRNA molecule is also bound to one and only one amino acid. Here's what they look like:
  
  A typical tRNA molecule. For clarity, the sugar-phosphate 'backbone' is shown as a long ribbon.
4. When the mRNA is bound to the ribosome, a tRNA comes along.
  1. If the tRNA doesn't have bases on the anticodon loop that are complementary with the first three mRNA base pairs, the tRNA falls back out of the ribosome, and another tRNA slots in.
  2. If the tRNA happens to be complementary to the mRNA, then the tRNA bonds to both the mRNA and the ribosome.
5. The ribosome then 'ratchets" down the mRNA by three nucleotides.
6. Another tRNA molecule pairs with the next mRNA codon.
7. Then a peptide bond is formed between the amino acids carried on the first and second tRNA molecules. . .
8. . . . . and the first tRNA molecule drops off.
9. Then the ribosome 'ratchets' down three more nucleotides. . .
10. . . . and the process repeats itself. . .
11. . . . . until the ribosome hits a 'stop' codon, which -- since this is RNA -- will be either UAA, UAG, or UGA. Then the ribosome falls apart, and the finished protein drops away.
Here's a diagram of the whole process (taken from an old exam of mine). Try covering up the caption and quizzing yourself:

1 -- nuclear membrane
2 -- messenger RNA
3 -- ribosome
4 -- chain of amino acids, soon to fold into a protein
5 -- transfer RNA

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