Molecular Genetics
Genetic Code
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The genetic code is a commaless, redundant, triplet code.
Facts
The genetic code, the key to conversion of nucleotide sequences to amino acid sequences, was uncovered before nucleotide sequences of genes could be determined. The process of uncovery included the following information:
- The code was triplet, meaning that groups of three nucleotides coded for a single amino acid. This was deduced from the genetic behavior of acridine-induced mutants of the T4 bacteriophage rII gene.
- Tobacco mosaic virus variants could be easily isolated. Amino acid analysis of the capsid proteins of the variants revealed that a given amino acid was usually replaced by only a few of the 20 possible amino acids.
- Khorana and colleagues synthesized defined sequence copolymers of di, tri and tetra nucleotides. They were used in vitro to program polypeptide synthesis on ribosomes. Selective incorporation of some but not other amino acids was observed (see table below).
|
UUU
UUC
UUA
UUG
|
phe
leu
|
UCU
UCC
UCA
UCG
|
ser |
UAU
UAC
UAA
UAG
|
tyr
stop
stop |
UGU
UGC
UGA
UGG
|
cys
stop
trp |
CUU
CUC
CUA
CUG
|
leu
|
CCU
CCC
CCA
CCG
|
pro |
CAU
CAC
CAA
CAG
|
his
gln |
CGU
CGC
CGA
CGG
|
arg |
AUU
AUC
AUA
AUG
|
ile
met |
ACU
ACC
ACA
ACG
|
thr |
AAU
AAC
AAA
AAG
|
asn
lys |
AGU
AGC
AGA
AGG
|
ser
arg |
GUU
GUC
GUA
GUG
|
val |
GCU
GCC
GCA
GCG
|
ala |
GAU
GAC
GAA
GAG
|
asp
glu |
GGU
GGC
GGA
GGG
|
gly |
| poly U |
poly phe |
- Nirenberg and Matthei found that oligonucleotide triplets stimulated amino acyl tRNA binding to ribosomes. Each triplet stimulated the binding of only one kind of charged tRNA.
|
poly C
|
poly pro |
| poly(U,G) |
mixed copolymer of phe, val, leu, cys, trp, gly |
| poly(UG) |
poly (cys.val) |
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Interpretations
- The genetic code is a triplet code, with three nucleotides coding for one amino acid.
- The code is commaless, there being no molecular signal to indicate where one codon stops and the next one starts. As a result the establishment of the frame of reading nucleotides by the intiation of translation is important for deciphering the genetic code.
- The genetic code is redundant, most amino acids being encoded by several codons. The preferred codons in a translated gene usually reflect the relative abundances of the corresponding tRNAs.
- The redundancy allows some flexibility in nucleotide sequence to accomodate nucleic acid secondary structure features and base composition preferences.
- The genetic code is practically universal. There are exceptions, however.
- Termination codons are expected on average once every 21 nucleotides. Regions of nucleotide sequences devoid of termination codons in one frame of reading are designated "open reading frames".
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Further information
- The development of techniques for nucleotide sequencing of RNA and DNA produced gene sequences that confirmed the conclusions of the above experiments.
- Exceptions to the universal code include (ref):
- Human mitochondria:
- AUA and AUG code for met
- AGA and AGG code for termination
- UGA codes for trp
- Fungal mitochondria
- UGA codes for trp in Saccharomyces
- CUN codes for leu (the standard coding) in Neurospora and Schizosaccharomyces but for thr in Saccharomyces cerevisiae
- Platyhelminth and Echinoderm mitochondria: AAA codes for asn
- Spiroplasma and mycoplasma mollicutes:
- UGA codes for trp
- CGG codes for termination
- Candida albicans: CUG can code for ser
- Certain Pichia species (P. stipitis and P. farinosa): CUG codes for Ser
- Micrococcus: AGA codes for termination
- Some ciliates: UAA and UGA code for gln.
- Other ciliates (Euplotes): UGA codes for cys
- The translation of poly(UG) into poly(cys.val) is frame independent. Similarly, Karposi's Sarcoma herpesvirus has a gene, K12, that is translated independently of reading frame. It consists primarily of a mulitply tandemly repeated 23 bp sequence. The sequence on one strand is devoid of A residues.
It thus lacks TAA, TAG and TGA stop codons in all three frames. Initiation at any CUG (inefficient relative to AUG) results in translation of a polypeptide of 23 amino acid residue repeats regardless of the frame of initiation! Frameshifting occurs at the end of each 23 nucleotide repeat as a consequence of the sequence.
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E-mail inquiries to U. Melcher------------Last Updated: 6 July, 2005
