Chapter 14 Opener
The Genetic Code
Lin, Ching-Hsuan (林晉玄)
Phone: 3366-4449
E-mail: chinghsuanlin@[Link]
The Code Is Degenerate
Codon: degeneracy
Anticodon: wobble
64 possibilities, but only have 20-amino-acids language
Degeneracy: each amino
acid is specified by more
than one codon
Synonyms: codons
specifying the same amino
acid
Coding role - Degeneracy
Often, when the first two
nucleotides are identical, the
third nucleotide can be either
C or U without changing the
code.
A and G at the third position
are interchangeable as well.
Minimize the deleterious effects of mutations
Reasons for degeneracy
Some tRNAs (a total of 40) could
recognize more than one different codons
(a total of 61).
The wobble feature of the base at the 5’
end of the anticodon (also called the
wobble position).
Wobble in the Anticodon
[Link]
ki/Francis_Crick
In 1966, Francis Crick devised the wobble
concept. It states that the base at the 5’ end
of the anticodon is not as spatially confined
as the other two, allowing it to form
hydrogen bonds with more than one bases
located at the 3’ end of a codon.
Why wobble is allowed at the 5’
anticodon? --the structural basis
The 3-D structure of tRNA shows that the stacking
interactions between the flat surfaces of the 3 anticodon
bases + 2 followed bases, and the first (5’) anticodon base
is positioned at the end of the stack, thus less restricted in
its movements.
The 3’ base appears in the middle of the stack, resulting in
the restriction of its movements.
The first (5’) anticodon base is positioned at the
end of the stack
Wobble in the Anticodon
Inosine Is the Fifith Base in the Anticodon
[Link]
Inosine arises through enzymatic modification
of adenine to give the 6-keto group
The Wobble Rules
The pairings permitted are those give
ribose-ribose distances close to that of
the standard A:U or G:C base pairs.
The ribose-ribose distances:
---Purine-purine: too long
---Pyrimidine-pyrimidine: too short
The ribose-ribose distances for
the wobble pairs are close to
those of A:U or G:C base pairs
Three Codons Direct Chain Termination
Three codons, UAA, UAG, and UGA signify
chain termination.
They are not read by tRNAs but by proteins
called release factors (RF1 and RF2 in bacteria
and eRF1 in eukaryotes).
Assignment of Codons Using Repeating
Copolymers Built from Two or Three Nucleotides
Three Rules Govern the Genetic Code
Codons are read in a 5’ to 3’ direction in units of three
nucleotides
Codons are nonoverlapping and the message contains
no gaps
The message is translated in a fixed reading frame
which is set by the initiation codon.
Three Kinds of Point Mutations
Alter the Genetic Code
Missense mutation: An alternation that changes a codon
specific for one amino acid to a codon specific for another
amino acid [Sense mutations do not alter genetic code]
Nonsense or stop mutation: An alternation causing a
change to a chain-termination codon
Frameshift mutation: mutations are insertions or
deletions of one or a small number of base pairs that
alter the reading frame
Ala Ala Ala Ala Ala Ala Ala Ala
5’ GCU GCU GCU GCU GCU GCU GCU GCU 3’
Frameshit
Ala Ala Ser Cys Cys Cys Cys Cys
5’ GCU GCU AGC UGC UGC UGC UGC UGC 3’
Frameshit 3 nucleotides
Ala Ala Ser Met Leu His Ala Ala
5’ GCU GCU AGC AUG CUG CAU GCU GCU 3’
The Harmful Mutations Can Be Reversed by a
Second Genetic Change
Reverse (back) mutations: change an altered nucleotide
sequence back to its original arrangement
Suppressor mutations: suppress the change due to
mutation at site A by producing an additional genetic
change at site B
(1) Intragenic suppression: same gene
(2) Intergenic suppression: another genes
Suppressor genes: genes that cause suppression of
mutations in other genes.
Suppression of Frame-Shift Mutations
(intragenic suppression)
Intergenic Suppression Involves Mutant tRNAs
Mutant tRNA genes suppress the effects of
nonsense mutations in protein-coding genes
They act by reading a stop codon as if it were a
signal for a specific amino acid
Intergenic Suppression Involves Mutant tRNAs
The Code Is Nearly Universal
Benefits of the universal codes
Allow us to directly compare the protein coding
sequences among all organisms (comparative
genomics)
Make it possible to express cloned copies of genes
encoding useful protein in different host organism.
Example: Human insulin expression in bacteria)
In certain subcellular organelles, the
genetic code is slightly different
Mitochondrial tRNAs are unusual in the way
that they decode mitochondrial messages
Only 22 tRNAs are present in mammalian
mitochondria. The U in the 5’ wobble position of
a tRNA is capable of recognizing all four bases in
the 3’ of the codon
Key points of the chapter
1. What is the degeneracy of genetic code? what is its importance?
and what is its molecular mechanisms?
2. What are the three roles governing the genetic code? What are
the mutations altering genetic code? What is the suppressor
mutation? and What are the best known intergenic suppressor
genes?
3. What are the benefits of the code universality?