CMB Lect 8 2011 Colour 2 Slides Per Page

8/13/2019 CMB Lect 8 2011 Colour 2 Slides Per Page

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Lecture 8

The Genetic Code andTranscri tional Control

BIOSCI 101: Cellular and Molecular Biology

Genetic code/transcriptional control

-

- in prokaryotes, mRNA may be polycistronic

- transcription and translation can be occurringsimultaneously in prokaryotes

- mRNA molecules undergo post-transcriptional


processing in eukaryotes- in eukaryotes transcription and translation are

separated by the nuclear membrane


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The flow of genetic information

BIOSCI 101: Cellular and Molecular BiologyCampbell 17.3

Coupled transcription and

translation in bacteria



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Transcription

andtranslation in

eu aryo es


Pro- and eukaryotic mRNA



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Genetic code/transcriptionalcontrol (contd)

a) the code is a triplet of nucleotides

- a triplet of nucleotides is called a codon

- for a triplet code, the possible combinations are4 x 4 x4 = 64


The tripletcode



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The genetic code (contd)

b) The code was deciphered using in vitrosystems

- a cell-free (in vitro) system for proteinsynthesis consists of extracts of E. coli containingribosomes, tRNA molecules and bacterial mRNA

- radioactive amino acids are incorporated into an


-

- experiments using synthetic mRNA molecules

demonstrated thati) mRNA is read sequentially

ii) how it is read depends on the reading frame

Deciphering the genetic code



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c) The code is degenerate

- most amino acids are specified by more thanone triplet

- there is >1 tRNA for some amino acids egleucine

- -


pairing only at the first two positions of the codon

and can tolerate a mis-match at the third (thewobble hypothesis) eg arginine

The geneticcode


Campbell 17.5


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d) The code is more or less universal

- the most usual start codon is AUG and the stopcodons are UAA, UAG and UGA

- comparison of nucleic acid and protein


sequences of molecules from a variety of pro-and eukaryotes confirmed the accuracy anduniversality of the code

- some differences in mitochondrial DNA coding

The genetic code is universal



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e) Changes in sequence cause mutations

- a mutation is any permanent, inheritablealteration in the DNA sequence

- may arise spontaneously, as a result of lowfrequency random errors, or may be induced


Genetic code/transcriptional

control (contd)


- point mutations involve a change in a singlebase pair. Can arise from :

i) mistakes in replication by DNA polymerase

ii) mutagenic agents eg UV light

iii) spontaneous chemical reactions in cells



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i) silent - no effect on the amino acid sequence

ii) missense - an amino acid is changed, maynot be serious

iii) nonsense - creation of a termination codon,usually serious

-


insertion or deletion of a base. Changes many

amino acids and usually causes complete lossof function

Changes may not be detected

Wild type

DNA template strand

5

3

3

5A

A A

A A A A

A AT

T T T T T

T T TT

C C C C

CG G G G

G

A

mRNA5

Protein

Amino end

Stop

Carboxyl end

3

Met Lys Phe Gly

A instead of G

(a) Nucleotide-pair substitution: silent

A CG A A A AG GGU U U U U


StopMet Lys Phe Gly

U instead of C

5 3A A A AT T T TTG G G GA

A G A A A AG GGU U U U U

T

U 35

Campbell 17.24


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Nucleotide-pairsubstitutions


Campbell 17.24

A single base change causessickle-cell disease

Wild-type hemoglobin Sick le-cell hemoglobin

Wild-type hemoglobin DNA

3

35 35

553

mRNA

A AG

C T T

mRNA

A

AG

T

T

Mutant hemoglobin DNA

C


Normal hemoglob in

Glu

Sickle-cell hemoglobin

Val


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Normal vs mutant haemoglobin



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Mapping malaria and the sickle-cell allele


Nucleotide-pairinsertions or

deletions


Campbell 17.24


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Genetic code/transcriptional

control (contd)

g) cells protect themselves from mutations

- fewer than 1 / 1000 random changes causes amutation

- most mutations are eliminated by DNA repair


mechanisms

Excisionrepa r o

damage


Campbell 16.19


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There are 61 mRNA codons that specify an amino acid, butonly about 32 tRNAs are actually required to translate them.

A practice question

A) some tRNAs have anticodons that recognize four or moredifferent codons.B) the rules for base pairing between the third base of acodon and tRNA are flexible.C) many codons are never used, so the tRNAs that recognizethem are dispensable.D Some tRNAs are easil destro ed b nucleases.


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CMB Lect 8 2011 Colour 2 Slides Per Page