Chapter 17: From Gene to Protein

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Chapter 17From Geneto Protein
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Important Point
If you are having trouble understanding lecture
material Try reading your text before
attending lectures. And take the time to read it
well!
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Flow of Information

• DNA ? DNA Replication
• DNA ? RNA Transcription
• RNA ? Protein Translation
• RNA ? DNA Reverse Transcription
• Protein ? RNA or DNA DOES NOT HAPPEN!
• Nucleic acid sequence is most readily translated
  into protein sequence
• But protein sequence cannot be translated into
  nucleic acid sequence
• In other words, information flows from Nucleic
  Acid Sequence to Protein Sequence
• Information flows from Genotype to Phenotype
• Mutation and Natural Selection supplies the means
  by which protein sequence can influence
  nucleic-acid sequence

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Flow of Information
The DNA inherited by an organism leads to
specific traits by dictating the synthesis of
certain proteins. Proteins are the links between
genotype and phenotype.
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Information Flow
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Information Flow
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Roles of Central Players

• A codon is a sequence of three nucleotides
• mRNA is the molecule that presents codons to
  ribosomes
• DNA serves as a codon-storage molecule
• DNA serves as a template for RNA synthesis
• Ribosomes translate codons, in sequence, into
  chains of amino-acids (polypeptides)
• These amino-acid (and RNA) sequences are
  precisely controlled
• Precision is both costly and requires complex
  machinery to achieve
• Once translated, proteins also are often
  post-translationally modified
• Proteins consist of one or more polypeptide

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Triplet Code
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Genetic Code
61 sense codons for 20 amino acids
Note the degeneracy of the triplet code
But also note the lack of ambiguity
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Genetic Code
mRNAs consist of a sequence of nucleotide
tripletscodonsthat code for amino acids and
which together are described as The Genetic Code
Note 3 stop codons nonsense codons
Note AUG, the start codon, codes for Methionine
(Met)
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Wobble

• Codons dont overlap, there is no punctuation,
  each codon codes for at most only one amino acid
  (lack of ambiguity in the code), many amino acids
  are coded by more than one codon ( degeneracy in
  the code)
• The cell would need tRNAs with 61 different
  anticodons to complement the available 61 codons
• However, due to the Degeneracy of the genetic
  code, the third base is less discriminatory for
  the amino acid than the other two bases
• This third position in the codon is referred to
  as the Wobble Position (and cells get by with 45
  tRNAs)
• Us and Cs may be read by a G in the anticodon
  As and Gs may be read by a U or y (pseudouridine)
• If a tRNA contains an inosine (I) in the
  anticodon at the wobble position, then this tRNA
  may read codons having As, Us or Cs in the third
  position

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Wobble one-codon A.A.s
AUG Met Methionine Start codon
UGG Trp Tryptophan Most expensive amino acid
All wobble discussion from http//www.nobel.se/med
icine/educational/dna/a/translation/trna_wobble.ht
ml
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Wobble 2- or 3-codon A.A.s
AAA AAG AAC AAU CAA CAG CAC CAU GAA GAG GAC GAU UAC UAU UGC UGU UUC UUU
Lys Asp Gln His Glu Asp Tyr Cys Phe
Lysine Aspartate Glutamine Histidine Glutamate Apartate Tyrosine Cysteine Phenylalanine
AUA AUC AUU
Ile
Isoleucine
AUG
Met
Methionine
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Wobble 4- or 6-codon A.A.s
ACA ACC ACG ACU CCA CCC CCG CCU GCA GCC GCG GCU GGA GGC GGG GGU GUA GUC GUG GUU
Thr Pro Ala Gly Val
Threonine Proline Alanine Glycine Valine
CGA AGA CGC AGG CGG CGU CUA UUA CUC UUG CUG CUU UCA AGC UCC AGU UCG UCU
Arg Leu Ser
Arginine Leucine Serine
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RNA Diversity

• Transcription makes various kinds of RNAs
• For example
• Messenger RNA (mRNA)
• Ribosomal RNA (rRNA)
• Transfer RNA (tRNA)
• Other (e.g., snRNA)
• RNAs may be matured in various ways (we will
  concentrate on mRNA maturation)
• Translation employs rRNAs and tRNAs to
  translate mRNA nucleotide/codon sequence into
  amino-acid sequence

About 60 of the mass of ribosomes is rRNA
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Types of RNA
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RNA Polymerase
Note 5 to 3 direction
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Transcription
Note that only one strand is serving as template
for transcription
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Initiation of Transcription
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mRNA Processing
Note Eucaryotes
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mRNA Splicing
Note Eucaryotes
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snRNPs Spliceosomes
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Exons Protein Domains
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Translation Overview
Remember that the primary goal of translation is
the synthesis of a polypeptide from mRNA-coded
information
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rRNAs have 2 Structure (e.g., 16S)
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tRNA 2D Structure
Note that the anticodon is more or less
complementary to the mRNA codon in terms of
base-pairing
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tRNA 3D Structure
No, you dont have to memorize this structure
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Aminoacyl tRNA Synthetases
Aminoacyl-tRNA synthetases are responsible for
tRNAs ability to precisely translate codon-based
code into amino-acid sequence
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Ribosome (in 3D)
You dont have to memorize structural detail
(e.g., the various bumps)
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Ribosome Schematic (empty)
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Ribosome Schematic (functioning)
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Translation, Initiation
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Translation, Elongation
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Translation, Termination
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Protein Targeting to ER
Polypeptides are subjected to a number of
post-translational modifications whether or not
they end up in the ER
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Secreting Proteins
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Polyribosomes
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Translation-Transcription Coupling
Works this way in bacteria
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Mutation
Mutations are alterations in DNA sequence that
result either in modified transcription (since
smaller target means less likely) or in modified
translation (which we shall dwell upon)
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Ultimate Source of Variation
Some mutations can be beneficial!
Some mutations are silent, not changing a.a.
sequence
Mutations are typically detrimental, but not
always
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Mutation BP Substitution
Understand the concept, dont memorize the
sequences!!!
Point mutations
Specifically, a missense mutation
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Sickle Cell Anemia Point Mutation
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Insertion / Deletion
Understand the concept, dont memorize the
sequences!!!
Reading frames start with AUG, have numerous
sense codons, and end with a stop codon
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What is a Gene?
Root Category Concept
Mendel Classical Genetics Discrete unit of inheritance
Morgan Chromosome Theory Locus on a chromosome
Watson Crick DNA Structure Sequence of nucleotides
Beadl Tatum Biochemistry one gene-one enzyme
Biochemistry one gene-one protein
Biochemistry one gene-one polypeptide
Modern Transcriptional one gene-one RNA
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Summary
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The End