Ch 12: Mechanisms of Transcription Ch 13: RNA Splicing Ch 14: Translation Ch 15: The Genetic Code
CHAPTER 15
DNA
Replicatio 1. Genetic information n transfer from polynucleotide chain into polypeptide chain. 2. Take place in ribosomes. 3. tRNAs recognize codons.
Many amino acids are specified by more than one codondegeneracy ( ). Codons specifying the same amino acid are called synonyms (
Coding role #1
1.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. 1.Transition in the third position of a codon specifies a same amino acid. Transversion in this position changes the amino acid about half the time.
CUG
CUC
Code degeneracy explains how there can be great variation in the AT/GC ratios in the DNA of various organisms without large changes in the proportion of amino acids in their proteins.
Coding role #2
1.The second position of a codon: Pyrimidines-hydrophobic amino acids Purines-polar amino acids 2.If the first two positions are both occupied by G or C, each of the four nucleotides in the third position specifies the same amino acid.
( ) Question: Is there a specific tRNA for every codon? (If it was true, at least 61 different tRNAs would exist.)
The answer is NO Some tRNA could recognize several different codons Inosine is present in the anticodon
Inosine
inosine
adenine
Wobble Concept
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.
G C A U I
U or C G U A or G A, U, or C
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:
The ribose-ribose distances for the wobble pairs are close to those of A:U or G:C base pairs Figure 15-2 Wobble base pairing
Critical Thinking
The wobble concept predicted that at least three tRNAs exist for the six serine codons (UCU, UCC, UCA, UCG, AGU, and AGC). Why?
The adjacent base is always a bulky modified purine residue. Figure 15-3 Structure of yeast tRNA(Phe)
Experimental Results: UUU codes for phenylalanine. CCC codes for proline. AAA codes for lysine. The guanine residues in poly-G firmly hydrogen bond to each other and form multistranded triple helices that do not bind to ribosomes.
Poly-AC contain 8 codons: CCC, CCA, CAC, ACC, CAA, ACA, AAC, and AAA. They code for Asp, Glu, His, Thr & Pro (CCC), Lys (AAA). The proportions of the 8 codons incorporated into polypeptide products depend on the A/C ratio
Such experiment can determine the composition of the codons, but not the order of the three nucleotides.
See Table 15-3 on Page 467
Transfer RNA Binding to Defined Trinucleotide Codons (1964) A method to order the nucleotides within some of the codons. Specific amino-acyl-tRNA can bind to ribosome-mRNA complexes. The addition of trinucleotide results in corresponding amino-
Amino Acids Codons Codon copolymer Recognized Incorporated or Assignment Polypeptide Made
(CU) UCU (UG) GUG (AC) CAC (AG) AGA|GAG|AGA Arginine ACA|CAC|ACA UGU|GUG|UGU Cystine Valine Threonine Histidine AGA ACA CUC|UCU|CUC Leucine 5-CUC-3 Serine UGU
Table 15-5
4/22/05
Three Rules
Codons are read in a 5 to 3 direction. 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.
1. Missense mutation: An alternation that changes a codon specific for one amino acid to a codon specific for another amino acid. 2. Nonsense or stop mutation: An alternation causing a change to a chain-termination codon.
3. Frameshift mutation: Insertions or deletions of one or a small number of base pairs that alter the reading frame.
Reverse the harmful mutations Reverse the harmful mutations by a second genetic change 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 (2) Intergenic suppression
Suppressor genes: genes that cause suppression of mutations in other genes. Suppressor mutations work by producing good (or partially good) copies of the protein that are made inactive by the original harmful mutation.
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.
Figure 15-7 a
Figure 15-7 a
Figure 15-7 b
The act of nonsense suppression is a competition between the suppressor tRNA and the release factor. In E. coli, Suppression of UAG codons is efficient, and suppression of UAA codon average is inefficient. Why??.
Suppressor mutations
4/22/05
The results of large-scale sequencing of genomes have confirmed the universality of the genetic code.
Benefits of the universal codes (1)Allow us to directly compare the protein coding sequences among all organisms. (2) Make it possible to express cloned copies of genes encoding useful protein in different host organism. Example: Human insulin ecpression in bacteria)
However, in certain subcellular organelles, the genetic code is slightly different from the standard code.
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.