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[[Image:RNA-codon.png|thumb|[[RNA]] codons.]]
[[Image:RNA-codon.png|thumb|[[RNA]] codons.]]
The '''genetic code''' is a set of rules that [[mapping|map]]s information encoded in messenger [[RNA]] sequences to [[amino acid]] sequences ([[protein]]s) in the living [[cell (biology)|cell]], and is employed in the process of [[protein biosynthesis]]. All living things use a code that is very similar to the '''standard genetic code'''. It is possible for a single organism to translate different parts of genome in different ways - in case of humans [[mitochondrion|mitochondria]] use slightly different genetic code than [[cell nucleus|nuclei]]. The code was identified in the 1960s.
The '''genetic code''' are the rules by which information encoded in [[DNA]] or [[RNA]] genetic material is translated into [[amino acid]] sequences of [[protein]]s in [[organism]]s through the intermediacy of discrete sequences or '''[[codons]]''' transcribed in [[messenger RNA]]. The code also specifies what amino acids are attached to [[tRNA]] "adaptor" molecules that carry specific amino acids required for the process of [[protein biosynthesis]]. Most organisms use a nearly universal code that is referred to as the '''standard genetic code'''. However, there are notable exceptions. It is also possible for a single organism to translate different parts of the genome in different ways. For example, in humans, protein synthesis in [[mitochondrion|mitochondria]] relies on a modified genetic code that varies from the standard one.


==History==
==Discovery==


After the structure of DNA was deciphered by [[James Watson]], [[Francis Crick]] and [[Rosalind Franklin]], serious efforts to understand the nature of the encoding of proteins began. [[George Gamov]] postulated that a three-letter code must be employed to encode the 20 different [[amino acid]]s used by living cells to encode proteins. The first actual deciphering of a codon was done by [[Marshall Nirenberg]] and Johann Matthaei in 1961. They used a cell-free system to [[translation (biology)|translate]] a poly-uracil RNA sequence (UUUUU..., etc.), and thereby deduced that the codon UUU specified the amino-acid [[phenylalanine]]. Subsequent work by [[Har Gobind Khorana]] identified the rest of the code, and shortly thereafter [[Robert Holley]] identified tRNA as the adapter molecule that facilitated translation. In 1968, Khorana, Holley and Nirenberg shared the [[Nobel Prize]] in Physiology or Medicine for their work.
After the structure of DNA was deciphered by [[James Watson]], [[Francis Crick]] and [[Rosalind Franklin]], serious efforts to understand the nature of the encoding of proteins began. [[George Gamov]] postulated that a three-letter code must be employed to encode the 20 different [[amino acid]]s used by living cells to encode proteins. The first elucidation of a codon was done by [[Marshall Nirenberg]] and [[Heinrich J. Matthaei]] in 1961 at the [[National Institutes of Health]]. They used a cell-free system to [[translation (biology)|translate]] a poly-uracil RNA sequence (or UUUUU... in biochemical terms) and discovered that the [[polypeptide]] they had synthesized consisted of only the amino acid [[phenylalanine]]. They, thereby deduced from this poly-phenylalanine that the codon UUU specified the amino-acid [[phenylalanine]]. Subsequent work by [[Har Gobind Khorana]] identified the rest of the code, and shortly thereafter [[Robert Holley]] identified [[transfer RNA]] as the adapter molecule that facilitated translation. In 1968, Khorana, Holley and Nirenberg shared the [[Nobel Prize]] in Physiology or Medicine for their work.


==Transfer of information via the genetic code==
==Genome expression==
The genetic information carried by an organism - its [[genome]] - is inscribed in one or more [[DNA]], or in some cases RNA, molecules. Each functional portion of a DNA or RNA molecule is referred to as a [[gene]]. Each gene is [[transcription (genetics)|transcribed]] into a short template molecule of the related polymer RNA, which is better suited for protein synthesis, [[messenger RNA]] (mRNA). This in turn is [[translation (genetics)|translated]] by mediation of a machinery consisting of [[ribosome]]s and a set of [[transfer RNA]]s and associated [[enzyme]]s into an [[amino acid]] chain (poly[[peptide]]), which will then be folded into a protein.
The genetic information carried by an organism, its [[genome]], is inscribed in one or more [[DNA]], or in some cases [[RNA]], molecules. Each functional portion of a DNA or RNA molecule is referred to as a [[gene]]. The gene sequence inscribed in DNA, and in RNA, is composed of tri-nucleotide units called '''codons''', each coding for a single amino acid. Each nucleotide sub-unit consists of a [[phosphate]], [[deoxyribose]] sugar and one of the 4 nitrogenous [[nucleotide]] bases grouped into 2 categories, [[purine]] and [[pyrimidine]]. The purine bases [[adenine]] ('''A''') and [[guanine]] ('''G''') are larger and consist of two aromatic rings. The pyrimidine bases [[cytosine]] ('''C''') and [[thymine]] ('''T''') are smaller and consist of only one aromatic ring. In RNA, however, thymine ('''T''') is substituted by [[uracil]] ('''U'''), and the deoxyribose is substituted by [[ribose]].


Each protein-coding gene is [[transcription (genetics)|transcribed]] into a short template molecule of the related polymer RNA, known as [[messenger RNA]] or mRNA. This in turn is [[translation (genetics)|translated]] on the [[ribosome]] into an [[amino acid]] chain or [[peptide|polypeptide]], which will then fold, resulting in secondary and tertiary structures. The process of translation requires [[transfer RNA]]s specific for individual amino acids with the amino acids [[covalent| covalently]] attached to them, [[guanosine triphosphate]] as an energy source, and a number of translation factors. tRNAs have anticodons complementary to the codons in mRNA and can be "charged" covalently with amino acids at their 3' terminal CCA ends. Individual tRNAs are charged with specific amino acids by enzymes known as [[aminoacyl tRNA synthetase]]s which have high specificity for both their cognate amino acids and tRNAs. The high specificity of these enzymes is a major reasons why the fidelity of protein translation is maintained.
The gene sequence inscribed in DNA, and in RNA, is composed of tri-nucleotide units called '''codons''', each coding for a single amino acid. Each nucleotide sub-unit consists of a [[phosphate]], [[deoxyribose]] sugar and one of the 4 nitrogenous [[nucleotide]] bases grouped into 2 categories, [[purine]] and [[pyrimidine]]. The purine bases [[adenine]] ('''A''') and [[guanine]] ('''G''') are larger and consist of two aromatic rings. The pyrimidine bases [[cytosine]] ('''C''') and [[thymine]] ('''T''') are smaller and consist of only one aromatic ring. In RNA, however, thymine ('''T''') is substituted by [[uracil]] ('''U'''), and the deoxyribose is substituted by [[ribose]].


Overall, there are 4³ = 64 different codon combinations. For example, the RNA sequence UUUAAACCC contains the codons UUU, AAA and CCC, each of which specifies one amino acid. So, this RNA sequence represents a protein sequence, three amino acids long. (DNA is also a sequence of nucleotide bases, but there [[thymine]] takes the place of uracil.)
Theoretically, there are 4³ = 64 different codon combinations possible with a triplet codon of three nucleotides. In reality, all 64 codons of the standard genetic code are assigned for either amino acids or stop signals during translation. If, for example, an RNA sequence, UUUAAACCC is considered and the '''[[Reading frames| reading-frame]]''' starts with the first U (by convention,[[DNA#Strand direction| 5' to 3']]), there are three codons, namely, UUU, AAA and CCC, each of which specifies one amino acid. This RNA sequence will be translated into an amino acid sequence, three amino acids long.


The standard genetic code is shown in the following tables. [[#Table 1: Codon Table|Table 1]] shows what amino acid each of the 64 codons specifies. [[#Table 2: Reverse Codon Table|Table 2]] shows what codons specify each of the 20 standard amino acids involved in translation. These are called forward and reverse codon tables, respectively. For example, the codon AAU represents the amino acid [[asparagine]] (Asn), and [[cysteine]] (Cys) is represented by UGU and by UGC.
The standard genetic code is shown in the following tables. [[#Table 1: Codon Table|Table 1]] shows what amino acid each of the 64 codons specifies. [[#Table 2: Reverse Codon Table|Table 2]] shows what codons specify each of the 20 standard amino acids involved in translation. These are called forward and reverse codon tables, respectively. For example, the codon AAU represents the amino acid [[asparagine]], and UGU and UGC represent [[cysteine]] {standard three-letter designations, Asn and Cys respectively).


==Table 1: RNA codon table==
==Table 1: RNA codon table==
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==Salient features==
[[Marshall W. Nirenberg]] and [[Heinrich J. Matthaei]] at the [[National Institutes of Health]] performed the experiments that first elucidated the correspondence between the codons and the amino acids that they code. [[Har Gobind Khorana]] expanded on Nirenberg's work and found the codes for the amino acids that Nirenberg's methods could not find. Khorana and Nirenberg won a share of the 1968 [[Nobel Prize in Physiology or Medicine]] for this work.
⚫
===Reading frame of a sequence ===
⚫
Note that a [[codon]] is defined by the inital nucleotide from which translation starts. For example, the string GGGAAACCC, if read from the first position, contains the codons GGG, AAA and CCC; if read from the second position, it contains the codons GGA and AAC; if read starting from the third position, GAA and ACC. Partial codons have been ignored in this example. Every sequence can thus be read in three '''[[reading frames]]''', each of which will produce a different amino acid sequence (in the given example, Gly-Lys-Pro, Gly-Asp, or Glu-Thr, respectively). With double-stranded DNA there are six possible [[reading frames]], three in the forward orientation on one strand and three reverse, or on the opposite strand.

⚫
The actual frame a protein sequence is translated in is defined by a '''[[start codon]]''', usually the first AUG codon in the mRNA sequence. Mutations that disrupt the reading frame by insertions or deletions of one or two nucleotide bases are knwon as [[frameshift mutation]]s. These mutations may impair the function of the resulting protein if it is formed and are thus rare in ''[[in vivo]]'' protein-coding sequences. Often such misformed proteins are targeted for proteolytic degradation. One reason for the rareness of frame-shifted mutations being inherited is that if the protein being translated is essential for growth under the selective pressures the organism faces, absence of a functional protein may cause lethality before the organism is viable.


==Technical details==
=== Start/stop codons ===
=== Start/stop codons ===


Translation starts with a chain [[start codon|initiation codon ]] ([[start codon]]). Unlike stop codons, the codon alone is not sufficient to begin the process, nearby sequences are also required to start translation upon binding by [[ribosome]]s. The most common start codon is AUG, which also codes for methionine, but other [[start codon]]s are also used.
Translation starts with a chain [[start codon|initiation codon ]] ([[start codon]]). Unlike stop codons, the codon alone is not sufficient to begin the process. Nearby sequences and [[initiation factor]]s are also required to start translation. The most common start codon is AUG, which also codes for methionine, but other [[start codon]]s are also used.


In classical genetics, the three stop codons were given names: UAG was ''amber'', UGA was ''opal'' (sometimes also called ''umber''), and UAA was ''ochre''. These names were originally the names of the specific genes in which mutation of each of these stop codons was first detected. Stop codons are also called termination codons.
The three stop codons have been given names: UAG is ''amber'', UGA is ''opal'' (sometimes also called ''umber''), and UAA is ''ochre''. These names are derived from the names of the specific genes in which mutation of each of these stop codons were first detected. Stop codons are also called termination codons and they signal release of the nascent polypeptide from the ribosome due to binding of [[release factor]]s in the absence of cognate tRNAs with anticodons complementary to these stop signals.


=== Degeneracy of the genetic code ===
=== Degeneracy of the genetic code ===
Many codons are '''redundant''', meaning that two or more codons can code for the same amino acid. Degenerate codons may differ in their third positions; e.g., both GAA and GAG code for the amino acid [[glutamic acid]]. A codon is said to be '''four-fold degenerate''' if any nucleotide at its third position specifies the same amino acid; it is said to be '''two-fold degenerate''' if only two of four possible nucleotides at its third position specify the same amino acid. In two-fold degenerate codons, the equivalent third position nucleotides are always either two [[purine]]s (A/G) or two [[pyrimidine]]s (C/T). The degeneracy of the genetic code is what accounts for the existence of [[silent mutations]].
Many codons are '''redundant''', meaning that two or more codons can code for the same amino acid. Degenerate codons may differ in their third positions; e.g., both GAA and GAG code for the amino acid [[glutamic acid]]. A codon is said to be '''four-fold degenerate''' if any nucleotide at its third position specifies the same amino acid; it is said to be '''two-fold degenerate''' if only two of four possible nucleotides at its third position specify the same amino acid. In two-fold degenerate codons, the equivalent third position nucleotides are always either two [[purine]]s (A/G) or two [[pyrimidine]]s (C/T). Only two amino acids are specified by a single codon; one of these is the amino-acid [[methionine]], specified by the codon AUG, which also specifies the start of translation; the other is [[tryptophan]], specified by the codon UGG.
The degeneracy of the genetic code is what accounts for the existence of [[silent mutations]].


Degeneracy is mandatory in order to produce enough different codons to code for 20 amino acids and a stop codon. Because there are four bases, triplet codons are required to produce at least 21 different codes. For example, if there were two bases per codon, then only 16 amino acids could be coded for (4²=16). Because at least 21 codes are required, then 4³ gives 64 possible codons, meaning that some degeneracy must exist.
Degeneracy results because a triplet code designates 20 amino acids and a stop codon. Because there are four bases, triplet codons are required to produce at least 21 different codes. For example, if there were two bases per codon, then only 16 amino acids could be coded for (4²=16). Because at least 21 codes are required, then 4³ gives 64 possible codons, meaning that some degeneracy must exist.


These properties of the genetic code make it more fault-tolerant for [[point mutation]]s. For example, four-fold degenerate codons can tolerate any point mutation at the third position; two-fold degenerate codons can tolerate one out of the three possible point mutations at the third position. Since transition mutations (purine to purine or pyrimidine to pyrimidine mutations) are more likely than transversion (purine to pyrimidine or vice-versa) mutations, the equivalence of purines or that of pyrimidines at two-fold degenerate sites adds a further fault-tolerance.
These properties of the genetic code make it more fault-tolerant for [[point mutation]]s. For example in theory, four-fold degenerate codons can tolerate any point mutation at the third position, although [[codon usage bias]] restricts this in practice in many organisms; two-fold degenerate codons can tolerate one out of the three possible point mutations at the third position. Since transition mutations (purine to purine or pyrimidine to pyrimidine mutations) are more likely than transversion (purine to pyrimidine or vice-versa) mutations, the equivalence of purines or that of pyrimidines at two-fold degenerate sites adds a further fault-tolerance.


A practical consequence of redundancy is that some errors in the genetic code only cause a silent mutation or an error that would not affect the amino acid's [[hydrophilic]]/[[hydrophobic]] property; e.g., a codon of NUN (where N = any nucleotide) tends to code for hydrophobic amino acids. Even so, it is a single point mutation that causes a modified [[hemoglobin]] molecule in [[sickle-cell disease]]. The hydrophilic [[glutamate]] (Glu) is substituted by the hydrophobic [[valine]] (Val), which reduces the solubility of ß-globin. This causes [[hemoglobin]] to form linear polymers linked by the hydrophobic interaction between the valine groups causing sickle-cell deformation of erythrocytes. Sickle-cell disease is generally not caused by a ''[[de novo]]'' mutation. Rather it is selected for in [[malaria|malarial]] regions (in a similar way to [[thalassemia]]), as [[heterozygote|heterozygous]] people have some resistance to the malarial ''[[Plasmodium]]'' parasite ([[heterozygote advantage]]).
A practical consequence of redundancy is that some errors in the genetic code only cause a silent mutation or an error that would not affect the protein becuase the [[hydrophilic|hydrophilicity]] or [[hydrophobic|hydrophobicity]] is maintained by equivalent substitutions of amino acids; for example, a codon of NUN (where N = any nucleotide) tends to code for hydrophobic amino acids. Even so, it is a single point mutation that causes a modified [[hemoglobin]] molecule in [[sickle-cell disease]]. The hydrophilic [[glutamate]] (Glu) is substituted by the hydrophobic [[valine]] (Val), which reduces the solubility of ß-globin. In this case, this mutation causes [[hemoglobin]] to form linear polymers linked by the hydrophobic interaction between the valine groups causing sickle-cell deformation of erythrocytes. Sickle-cell disease is generally not caused by a ''[[de novo]]'' mutation. Rather it is selected for in [[malaria|malarial]] regions (in a similar way to [[thalassemia]]), as [[heterozygote|heterozygous]] people have some resistance to the malarial ''[[Plasmodium]]'' parasite ([[heterozygote advantage]]).


⚫
These variable codes for amino acids are allowed because of modified bases in the first base of the [[anticodon]] of the tRNA, and the base-pair formed is called a [[wobble base pair]]. The modified bases include [[inosine]] and the Non-Watson-Crick U-G basepair.
In general, these properties are widely interpreted to form part of the reason for the origin of the standard genetic code [see below].


In general, properties of the genetic code have used to theorize on the origin of the genetic code, as discussed in a following section.
⚫
These variable codes for amino acids are possible because of modified bases in the first base of the [[anticodon]], and the basepair formed is called a [[wobble base pair]]. The modified bases include [[inosine]] and the U-G basepair.

Only two amino acids are specified by a single codon; one of these is the amino-acid [[methionine]], specified by the codon AUG, which also specifies the start of translation; the other is [[tryptophan]], specified by the codon UGG.

⚫
=== Phase or reading frame of a sequence ===
⚫
Note that a "[[codon]]" is entirely defined by your starting position. For example, the string GGGAAACCC, if read from the first position, contains the codons GGG, AAA and CCC. If read from the second position, it contains the codons GGA and AAC (partial codons being ignored here). If read starting from the third position, GAA and ACC. Every sequence can thus be read in three '''[[reading frames]]''', each of which will produce a radically different amino acid sequence (in our example, Gly-Lys-Pro, Gly-Asp, and Glu-Thr, respectively). On double stranded DNA there are six possible [[reading frames]], three forward and three reverse.

⚫
The actual frame a protein sequence is translated in is defined by a '''[[start codon]]''', usually the first occurrence of AUG in the mRNA sequence. Mutations that disrupt the reading frame (i.e. insertions or deletions of one or two nucleotide bases, [[frameshift mutation]]s) severely impair the function of a protein and are thus exceedingly rare in ''[[in vivo]]'' protein-coding sequences, since they often lead to death before an organism is viable.


==Variations==
==Variations==


Numerous variations of the standard genetic code are found in [[mitochondrion|mitochondria]], which are energy-producing organelles that reside inside eukaryotic cells. [[Mycoplasma]] translate the codon UGA as tryptophan. [[Ciliate]] [[protozoa]] also have some variation in the genetic code: UAG and often UAA code for glutamine (a variant also found in some [[green alga]]e), or UGA codes for cysteine. Another variant is found in some species of the [[yeast]] [[Candida (genus)|candida]], where CUG codes for [[serine]]. In addition in some rare cases certain proteins may also use alternate initiation (start) codons.
Numerous variations of the standard genetic code are found in [[mitochondrion|mitochondria]], which are energy-producing organelles that are found inside eukaryotic cells. ''[[Mycoplasma]]'' translate the codon UGA as tryptophan. [[Ciliate]] [[protozoa]] also have some variation in the genetic code: UAG and often UAA code for glutamine (a variant also found in some [[green alga]]e), or UGA codes for cysteine. Another variant is found in some species of the [[yeast]], ''[[Candida (genus)|Candida]]'', where CUG codes for [[serine]]. In addition in some rare cases certain proteins may also use alternate initiation (start) codons.

In certain proteins, non-standard amino acids are substituted for standard stop codons, depending upon associated signal sequences in the messenger RNA: UGA can code for [[selenocysteine]] and UAG can code for [[pyrrolysine]] (for details, see the articles on these two amino acids). There may be other non-standard interpretations that are not yet known.


A detailed description of variations in the genetic code can be found at the [http://www.ncbi.nlm.nih.gov/Taxonomy/Utils/wprintgc.cgi?mode=c NCBI web site].
In certain proteins, non-standard amino acids are substituted for standard stop codons, depending upon associated signal sequences in the messenger RNA: UGA can code for [[selenocysteine]] and UAG can code for [[pyrrolysine]] as discussed in the relevant articles. A detailed description of variations in the genetic code can be found at the [http://www.ncbi.nlm.nih.gov/Taxonomy/Utils/wprintgc.cgi?mode=c NCBI web site]. However, there may be other non-standard interpretations that are not yet known. Sequencing of genomes may reveal unique genetic codes that allow the incorporation of other novel amino acids into proteins.


==Origin of the genetic code==
==Origin of the genetic code==

Revision as of 06:28, 21 September 2006

RNA codons.

The genetic code are the rules by which information encoded in DNA or RNA genetic material is translated into amino acid sequences of proteins in organisms through the intermediacy of discrete sequences or codons transcribed in messenger RNA. The code also specifies what amino acids are attached to tRNA "adaptor" molecules that carry specific amino acids required for the process of protein biosynthesis. Most organisms use a nearly universal code that is referred to as the standard genetic code. However, there are notable exceptions. It is also possible for a single organism to translate different parts of the genome in different ways. For example, in humans, protein synthesis in mitochondria relies on a modified genetic code that varies from the standard one.

Discovery

After the structure of DNA was deciphered by James Watson, Francis Crick and Rosalind Franklin, serious efforts to understand the nature of the encoding of proteins began. George Gamov postulated that a three-letter code must be employed to encode the 20 different amino acids used by living cells to encode proteins. The first elucidation of a codon was done by Marshall Nirenberg and Heinrich J. Matthaei in 1961 at the National Institutes of Health. They used a cell-free system to translate a poly-uracil RNA sequence (or UUUUU... in biochemical terms) and discovered that the polypeptide they had synthesized consisted of only the amino acid phenylalanine. They, thereby deduced from this poly-phenylalanine that the codon UUU specified the amino-acid phenylalanine. Subsequent work by Har Gobind Khorana identified the rest of the code, and shortly thereafter Robert Holley identified transfer RNA as the adapter molecule that facilitated translation. In 1968, Khorana, Holley and Nirenberg shared the Nobel Prize in Physiology or Medicine for their work.

Transfer of information via the genetic code

The genetic information carried by an organism, its genome, is inscribed in one or more DNA, or in some cases RNA, molecules. Each functional portion of a DNA or RNA molecule is referred to as a gene. The gene sequence inscribed in DNA, and in RNA, is composed of tri-nucleotide units called codons, each coding for a single amino acid. Each nucleotide sub-unit consists of a phosphate, deoxyribose sugar and one of the 4 nitrogenous nucleotide bases grouped into 2 categories, purine and pyrimidine. The purine bases adenine (A) and guanine (G) are larger and consist of two aromatic rings. The pyrimidine bases cytosine (C) and thymine (T) are smaller and consist of only one aromatic ring. In RNA, however, thymine (T) is substituted by uracil (U), and the deoxyribose is substituted by ribose.

Each protein-coding gene is transcribed into a short template molecule of the related polymer RNA, known as messenger RNA or mRNA. This in turn is translated on the ribosome into an amino acid chain or polypeptide, which will then fold, resulting in secondary and tertiary structures. The process of translation requires transfer RNAs specific for individual amino acids with the amino acids covalently attached to them, guanosine triphosphate as an energy source, and a number of translation factors. tRNAs have anticodons complementary to the codons in mRNA and can be "charged" covalently with amino acids at their 3' terminal CCA ends. Individual tRNAs are charged with specific amino acids by enzymes known as aminoacyl tRNA synthetases which have high specificity for both their cognate amino acids and tRNAs. The high specificity of these enzymes is a major reasons why the fidelity of protein translation is maintained.

Theoretically, there are 4³ = 64 different codon combinations possible with a triplet codon of three nucleotides. In reality, all 64 codons of the standard genetic code are assigned for either amino acids or stop signals during translation. If, for example, an RNA sequence, UUUAAACCC is considered and the reading-frame starts with the first U (by convention, 5' to 3'), there are three codons, namely, UUU, AAA and CCC, each of which specifies one amino acid. This RNA sequence will be translated into an amino acid sequence, three amino acids long.

The standard genetic code is shown in the following tables. Table 1 shows what amino acid each of the 64 codons specifies. Table 2 shows what codons specify each of the 20 standard amino acids involved in translation. These are called forward and reverse codon tables, respectively. For example, the codon AAU represents the amino acid asparagine, and UGU and UGC represent cysteine {standard three-letter designations, Asn and Cys respectively).

Table 1: RNA codon table

This table shows the 64 codons and the amino acid each codon codes for. The direction is 5' to 3'.
2nd base
U C A G
1st
base		 U

UUU (Phe/F)Phenylalanine
UUC (Phe/F)Phenylalanine
UUA (Leu/L)Leucine
UUG (Leu/L)Leucine

UCU (Ser/S)Serine
UCC (Ser/S)Serine
UCA (Ser/S)Serine
UCG (Ser/S)Serine

UAU (Tyr/Y)Tyrosine
UAC (Tyr/Y)Tyrosine
UAA Ochre (Stop)
UAG Amber (Stop)

UGU (Cys/C)Cysteine
UGC (Cys/C)Cysteine
UGA Opal (Stop)
UGG (Trp/W)Tryptophan
C

CUU (Leu/L)Leucine
CUC (Leu/L)Leucine
CUA (Leu/L)Leucine
CUG (Leu/L)Leucine

CCU (Pro/P)Proline
CCC (Pro/P)Proline
CCA (Pro/P)Proline
CCG (Pro/P)Proline

CAU (His/H)Histidine
CAC (His/H)Histidine
CAA (Gln/Q)Glutamine
CAG (Gln/Q)Glutamine

CGU (Arg/R)Arginine
CGC (Arg/R)Arginine
CGA (Arg/R)Arginine
CGG (Arg/R)Arginine
A

AUU (Ile/I)Isoleucine
AUC (Ile/I)Isoleucine
AUA (Ile/I)Isoleucine
AUG (Met/M)Methionine, Start1

ACU (Thr/T)Threonine
ACC (Thr/T)Threonine
ACA (Thr/T)Threonine
ACG (Thr/T)Threonine

AAU (Asn/N)Asparagine
AAC (Asn/N)Asparagine
AAA (Lys/K)Lysine
AAG (Lys/K)Lysine

AGU (Ser/S)Serine
AGC (Ser/S)Serine
AGA (Arg/R)Arginine
AGG (Arg/R)Arginine
G

GUU (Val/V)Valine
GUC (Val/V)Valine
GUA (Val/V)Valine
GUG (Val/V)Valine

GCU (Ala/A)Alanine
GCC (Ala/A)Alanine
GCA (Ala/A)Alanine
GCG (Ala/A)Alanine

GAU (Asp/D)Aspartic acid
GAC (Asp/D)Aspartic acid
GAA (Glu/E)Glutamic acid
GAG (Glu/E)Glutamic acid

GGU (Gly/G)Glycine
GGC (Gly/G)Glycine
GGA (Gly/G)Glycine
GGG (Gly/G)Glycine

1The codon AUG both codes for methionine and serves as an initiation site: the first AUG in an mRNA's coding region is where translation into protein begins.

Table 2: Reverse codon table

This table shows the 20 standard amino acids used in proteins, and the codons that code for each amino acid.

Ala A GCU, GCC, GCA, GCG Leu L UUA, UUG, CUU, CUC, CUA, CUG
Arg R CGU, CGC, CGA, CGG, AGA, AGG Lys K AAA, AAG
Asn N AAU, AAC Met M AUG
Asp D GAU, GAC Phe F UUU, UUC
Cys C UGU, UGC Pro P CCU, CCC, CCA, CCG
Gln Q CAA, CAG Ser S UCU, UCC, UCA, UCG, AGU,AGC
Glu E GAA, GAG Thr T ACU, ACC, ACA, ACG
Gly G GGU, GGC, GGA, GGG Trp W UGG
His H CAU, CAC Tyr Y UAU, UAC
Ile I AUU, AUC, AUA Val V GUU, GUC, GUA, GUG
Start AUG Stop UAG, UGA, UAA

Salient features

Reading frame of a sequence

Note that a codon is defined by the inital nucleotide from which translation starts. For example, the string GGGAAACCC, if read from the first position, contains the codons GGG, AAA and CCC; if read from the second position, it contains the codons GGA and AAC; if read starting from the third position, GAA and ACC. Partial codons have been ignored in this example. Every sequence can thus be read in three reading frames, each of which will produce a different amino acid sequence (in the given example, Gly-Lys-Pro, Gly-Asp, or Glu-Thr, respectively). With double-stranded DNA there are six possible reading frames, three in the forward orientation on one strand and three reverse, or on the opposite strand.

The actual frame a protein sequence is translated in is defined by a start codon, usually the first AUG codon in the mRNA sequence. Mutations that disrupt the reading frame by insertions or deletions of one or two nucleotide bases are knwon as frameshift mutations. These mutations may impair the function of the resulting protein if it is formed and are thus rare in in vivo protein-coding sequences. Often such misformed proteins are targeted for proteolytic degradation. One reason for the rareness of frame-shifted mutations being inherited is that if the protein being translated is essential for growth under the selective pressures the organism faces, absence of a functional protein may cause lethality before the organism is viable.

Start/stop codons

Translation starts with a chain initiation codon (start codon). Unlike stop codons, the codon alone is not sufficient to begin the process. Nearby sequences and initiation factors are also required to start translation. The most common start codon is AUG, which also codes for methionine, but other start codons are also used.

The three stop codons have been given names: UAG is amber, UGA is opal (sometimes also called umber), and UAA is ochre. These names are derived from the names of the specific genes in which mutation of each of these stop codons were first detected. Stop codons are also called termination codons and they signal release of the nascent polypeptide from the ribosome due to binding of release factors in the absence of cognate tRNAs with anticodons complementary to these stop signals.

Degeneracy of the genetic code

Many codons are redundant, meaning that two or more codons can code for the same amino acid. Degenerate codons may differ in their third positions; e.g., both GAA and GAG code for the amino acid glutamic acid. A codon is said to be four-fold degenerate if any nucleotide at its third position specifies the same amino acid; it is said to be two-fold degenerate if only two of four possible nucleotides at its third position specify the same amino acid. In two-fold degenerate codons, the equivalent third position nucleotides are always either two purines (A/G) or two pyrimidines (C/T). Only two amino acids are specified by a single codon; one of these is the amino-acid methionine, specified by the codon AUG, which also specifies the start of translation; the other is tryptophan, specified by the codon UGG. The degeneracy of the genetic code is what accounts for the existence of silent mutations.

Degeneracy results because a triplet code designates 20 amino acids and a stop codon. Because there are four bases, triplet codons are required to produce at least 21 different codes. For example, if there were two bases per codon, then only 16 amino acids could be coded for (4²=16). Because at least 21 codes are required, then 4³ gives 64 possible codons, meaning that some degeneracy must exist.

These properties of the genetic code make it more fault-tolerant for point mutations. For example in theory, four-fold degenerate codons can tolerate any point mutation at the third position, although codon usage bias restricts this in practice in many organisms; two-fold degenerate codons can tolerate one out of the three possible point mutations at the third position. Since transition mutations (purine to purine or pyrimidine to pyrimidine mutations) are more likely than transversion (purine to pyrimidine or vice-versa) mutations, the equivalence of purines or that of pyrimidines at two-fold degenerate sites adds a further fault-tolerance.

A practical consequence of redundancy is that some errors in the genetic code only cause a silent mutation or an error that would not affect the protein becuase the hydrophilicity or hydrophobicity is maintained by equivalent substitutions of amino acids; for example, a codon of NUN (where N = any nucleotide) tends to code for hydrophobic amino acids. Even so, it is a single point mutation that causes a modified hemoglobin molecule in sickle-cell disease. The hydrophilic glutamate (Glu) is substituted by the hydrophobic valine (Val), which reduces the solubility of ß-globin. In this case, this mutation causes hemoglobin to form linear polymers linked by the hydrophobic interaction between the valine groups causing sickle-cell deformation of erythrocytes. Sickle-cell disease is generally not caused by a de novo mutation. Rather it is selected for in malarial regions (in a similar way to thalassemia), as heterozygous people have some resistance to the malarial Plasmodium parasite (heterozygote advantage).

These variable codes for amino acids are allowed because of modified bases in the first base of the anticodon of the tRNA, and the base-pair formed is called a wobble base pair. The modified bases include inosine and the Non-Watson-Crick U-G basepair.

In general, properties of the genetic code have used to theorize on the origin of the genetic code, as discussed in a following section.

Variations

Numerous variations of the standard genetic code are found in mitochondria, which are energy-producing organelles that are found inside eukaryotic cells. Mycoplasma translate the codon UGA as tryptophan. Ciliate protozoa also have some variation in the genetic code: UAG and often UAA code for glutamine (a variant also found in some green algae), or UGA codes for cysteine. Another variant is found in some species of the yeast, Candida, where CUG codes for serine. In addition in some rare cases certain proteins may also use alternate initiation (start) codons.

In certain proteins, non-standard amino acids are substituted for standard stop codons, depending upon associated signal sequences in the messenger RNA: UGA can code for selenocysteine and UAG can code for pyrrolysine as discussed in the relevant articles. A detailed description of variations in the genetic code can be found at the NCBI web site. However, there may be other non-standard interpretations that are not yet known. Sequencing of genomes may reveal unique genetic codes that allow the incorporation of other novel amino acids into proteins.

Origin of the genetic code

Despite the variations that exist, the genetic codes used by all known forms of life on Earth are very similar. Since there are many possible genetic codes that are thought to have similar utility to the one used by Earth life, the theory of evolution suggests that the genetic code was established very early in the history of life.

One can ask the question: is the genetic code completely random, just one set of codon-amino acid correspondences that happened to establish itself and be "frozen in" early in evolution, although functionally any of the many other possible transcription tables would have done just as well? Already a cursory look at the table shows patterns that suggest that this is not the case.

There are three themes running through the many theories that seek to explain the evolution of the genetic code (and hence the origin of these patterns)Template:Fn. One is illustrated by recent aptamer experiments which show that some amino acids have a selective chemical affinity for the base triplets that code for them.Template:Fn This suggests that the current, complex transcription mechanism involving tRNA and associated enzymes may be a later development, and that originally, protein sequences were directly templated on base sequences. Another is that the standard genetic code that we see today grew from a simpler, earlier code through a process of "biosynthetic expansion". Here the idea is that primordial life 'invented' new amino acids (e.g. as by-products of metabolism) and later back-incorporated some of these into the machinery of genetic coding. Although much circumstantial evidence has been found to indicate that originally the number of different amino acids used may have been considerably smaller than todayTemplate:Fn, precise and detailed hypotheses about exactly which amino acids entered the code in exactly what order has proved far more controversialTemplate:Fn,Template:Fn. A third is that natural selection organized the codon assignments of the genetic code to minimize the effects of genetic errors (mutations)Template:Fn.

Other resources

There are several books available online that go into great detail on this topic. They are available through the NCBI Bookshelf, maintained by the United States National Institutes of Health. In particular the following books would be useful to consult.

  • Griffiths, Anthony J.F.; Miller, Jeffrey H.; Suzuki, David T.; Lewontin, Richard C.; Gelbart, William M. (1999). Introduction to Genetic Analysis (7th ed.). New York: W. H. Freeman & Co. ISBN 0-7167-3771-X
  • Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter. (2002). Molecular Biology of the Cell (4th ed.). New York: Garland Publishing. ISBN 0-8153-3218-1
  • Lodish, Harvey; Berk, Arnold; Zipursky, S. Lawrence; Matsudaira, Paul; Baltimore, David; Darnell, James E. (1999). Molecular Cell Biology (4th ed.). New York: W. H. Freeman & Co. ISBN 0-7167-3706-X

There is also a themed wiki devoted to the topic of how the genetic code evolved, and its effects on the subsequent evolution of the genome:

References

See also

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