How Genes Work

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How Genes Work

• Chapter 15

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What do genes do?
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How do genes work?

• Genes carry the instructions for making and
  maintaining an individual
• But how is this information translated into
  action?
• How does an organisms genotype specify its
  phenotype?

RR
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Garrod

• Provided the first clue to gene function
• studied alkaptonuria, a disease in which
  homogentisic acid is secreted in the urine.
• Hypothesized that the metabolic pathway in which
  homogentisic acid is an intermediate must be
  blocked in alkaptonurics
• Block due to lack of an enzyme that breaks down
  homogentisic acid, leading to its buildup.

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Garrod
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George Beadle and Edward Tatum

• Developed the one-gene, one-enzyme hypothesis
  from Garrods work
• Each gene carries the information for one protein
  or enzyme.
• Did experiments using red bread mold Neurospora
  crassa
• Irradiated mold to create mutants
• Tested if they could grow on minimal media
• Adrian Srb and Norman Horowitz tested for arginine

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Adrian Srb and Norman Horowitz
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Adrian Srb and Norman Horowitz

• Followed work by Krebs showing that cells from
  mammals synthesize arginine via a series of steps
  and that ornithine and citrulline act as
  intermediates
• Enzymes are required to convert ornithine to
  citrulline and citrulline to arginine

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Adrian Srb and Norman Horowitz

• Set out to link the biochemistry to genetics
• Used a genetic screen
• Technique for picking certain types of mutants
  out of many thousands of randomly generated
  mutants
• Isolated knock-out mutants
• inable to grow in the absence of arginine
• Indicating that the biosynthetic pathway was not
  functioning properly

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Adrian Srb and Norman Horowitz

• Grew the mutants on intermediates of arginine
  pathway to figure out where pathway was blocked
• Mutants were able to grow in the presence of an
  intermediate in the pathway downstream, but not
  upstream, of the blocked step
• Demonstrated that each type of mutant lacked the
  enzyme responsible for a certain step in the
  pathway

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The Gene

• Crick proposed that the sequence of the bases in
  DNA is a kind of code
• Information storage molecule
• A particular stretch of DNA (a gene) contains the
  information to specify the amino acid sequence of
  only one protein.

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RNA

• Francois Jacob and
• Jacques Monod
• proposed the
• Messenger RNA (mRNA)
• hypothesis
• RNA is the intermediary
• between DNA and protein
• Carries information from DNA to the site of
  protein synthesis

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RNA

• RNA polymerase synthesizes mRNA by reading DNA
  sequences
• Transcribes one strand of the DNA, making a
  complementary RNA copy

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The Genetic Code

• George Gamow predicted that each word (codon) in
  the genetic code would be three nucleotides long
• Minimum code length that could specify the 20
  different amino acids found in proteins
• This triplet code is redundant, with some amino
  acids being specified by more than one codon

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The Genetic Code
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The Genetic Code

• Francis Crick and colleagues established that the
  code is indeed based on three nucleotides for
  each amino acid
• Used insertion and deletion mutations
• Reading frame (sequence of codons) of a gene
  could be destroyed by mutation
• Restored if the total number of deletions or
  additions were multiples of three

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(No Transcript)
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The Genetic Code
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DNA to Protein
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DNA

• Long-term information storage unit
• Allows for the stable maintenance of the
  information and its passage from generation to
  generation
• RNA carries the information from the DNA to the
  translation machinery (ribosomes)
• RNA is ephemeral
• Allows for preservation of the DNA
• Proteins carry out cellular functions

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Genes ultimately code for proteins

• DNA is the hereditary material.
• Genes consist of specific stretches of DNA.
• The sequence of bases in DNA specifies the
  sequence of bases in an RNA molecule.
• Groups of three bases within a sequence of mRNA
  specify the sequence of amino acids in a protein.

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Proteins

• Most proteins function as enzymes
• Motor proteins and contractile proteins move the
  cell itself or cellular cargo.
• Peptide hormones carry signals from cell to cell.
• Transport proteins conduct specific ions or
  molecules across the plasma membrane.
• Antibodies and other immune system proteins
  recognize and destroy invading viruses and
  bacteria