Genetic code

"Codon" redirects here. For the plant genus, see Codon (genus).
A series of codons in part of a messenger RNA (mRNA) molecule. Each codon consists of three nucleotides, usually corresponding to a single amino acid. The nucleotides are abbreviated with the letters A, U, G and C. This is mRNA, which uses U (uracil). DNA uses T (thymine) instead. This mRNA molecule will instruct a ribosome to synthesize a protein according to this code.

The genetic code is the set of rules by which information encoded within genetic material (DNA or mRNA sequences) can be both translated into proteins by living cells or transcribed into non-coding RNAs that serve as regulatory tools in gene regulation. Biological decoding is accomplished by the ribosome, which links amino acids in an order specified by mRNA, using transfer RNA (tRNA) molecules to carry amino acids and to read the mRNA three nucleotides at a time. The genetic code is highly similar among all organisms and can be expressed in a simple table with 64 entries.

The code defines how sequences of nucleotide triplets, called codons, specify which amino acid will be added next during protein synthesis. With some exceptions,[1] a three-nucleotide codon in a nucleic acid sequence specifies a single amino acid. Because the vast majority of genes are encoded with exactly the same code (see the RNA codon table), this particular code is often referred to as the canonical or standard genetic code, or simply the genetic code, though in fact some variant codes have evolved. For example, protein synthesis in human mitochondria relies on a genetic code that differs from the standard genetic code.

While the genetic code determines the protein sequence for a given coding region, other genomic regions can influence when and where these proteins are produced.

Discovery

The genetic code

Serious efforts to understand how proteins are encoded began after the structure of DNA was discovered in 1953. George Gamow postulated that sets of three bases must be employed to encode the 20 standard amino acids used by living cells to build proteins. With four different nucleotides, a code of 2 nucleotides would allow for only a maximum of 42 = 16 amino acids. A code of 3 nucleotides could code for a maximum of 43 = 64 amino acids.[2]

The Crick, Brenner et al. experiment first demonstrated that codons consist of three DNA bases; Marshall Nirenberg and Heinrich J. Matthaei were the first to elucidate the nature of a codon in 1961 at the National Institutes of Health. They used a cell-free system to translate a poly-uracil RNA sequence (i.e., UUUUU...) and discovered that the polypeptide that they had synthesized consisted of only the amino acid phenylalanine.[3] They thereby deduced that the codon UUU specified the amino acid phenylalanine. This was followed by experiments in Severo Ochoa's laboratory that demonstrated that the poly-adenine RNA sequence (AAAAA...) coded for the polypeptide poly-lysine[4] and that the poly-cytosine RNA sequence (CCCCC...) coded for the polypeptide poly-proline.[5] Therefore, the codon AAA specified the amino acid lysine, and the codon CCC specified the amino acid proline. Using different copolymers most of the remaining codons were then determined. Subsequent work by Har Gobind Khorana identified the rest of the genetic code. Shortly thereafter, Robert W. Holley determined the structure of transfer RNA (tRNA), the adapter molecule that facilitates the process of translating RNA into protein. This work was based upon earlier studies by Severo Ochoa, who received the Nobel Prize in Physiology or Medicine in 1959 for his work on the enzymology of RNA synthesis.[6]

Extending this work, Nirenberg and Philip Leder revealed the triplet nature of the genetic code and deciphered the codons of the standard genetic code. In these experiments, various combinations of mRNA were passed through a filter that contained ribosomes, the components of cells that translate RNA into protein. Unique triplets promoted the binding of specific tRNAs to the ribosome. Leder and Nirenberg were able to determine the sequences of 54 out of 64 codons in their experiments.[7] In 1968, Khorana, Holley and Nirenberg received the Nobel Prize in Physiology or Medicine for their work.[8]

Salient features

Sequence reading frame

A codon is defined by the initial nucleotide from which translation starts. For example, the string GGGAAACCC, if read from the first position, contains the codons GGG, AAA, and CCC; and, if read from the second position, it contains the codons GGA and AAC; if read starting from the third position, GAA and ACC. Every sequence can, thus, be read in its 5' → 3' direction in three reading frames, each of which will produce a different amino acid sequence (in the given example, Gly-Lys-Pro, Gly-Asn, 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 on the opposite strand.[9]:330 The actual frame from which a protein sequence is translated is defined by a start codon, usually the first AUG codon in the mRNA sequence.

Start/stop codons

Translation starts with a chain initiation codon or start codon. Unlike stop codons, the codon alone is not sufficient to begin the process. Nearby sequences such as the Shine-Dalgarno sequence in E. coli and initiation factors are also required to start translation. The most common start codon is AUG, which is read as methionine or, in bacteria, as formylmethionine. Alternative start codons depending on the organism include "GUG" or "UUG"; these codons normally represent valine and leucine, respectively, but as start codons they are translated as methionine or formylmethionine.[10]

The three stop codons have been given names: UAG is amber, UGA is opal (sometimes also called umber), and UAA is ochre. "Amber" was named by discoverers Richard Epstein and Charles Steinberg after their friend Harris Bernstein, whose last name means "amber" in German.[11] The other two stop codons were named "ochre" and "opal" in order to keep the "color names" theme. Stop codons are also called "termination" or "nonsense" codons. They signal release of the nascent polypeptide from the ribosome because there is no cognate tRNA that has anticodons complementary to these stop signals, and so a release factor binds to the ribosome instead.[12]

Effect of mutations

Examples of notable mutations that can occur in humans.[13]

During the process of DNA replication, errors occasionally occur in the polymerization of the second strand. These errors, called mutations, can have an impact on the phenotype of an organism, especially if they occur within the protein coding sequence of a gene. Error rates are usually very low—1 error in every 10–100 million bases—due to the "proofreading" ability of DNA polymerases.[14][15]

Missense mutations and nonsense mutations are examples of point mutations, which can cause genetic diseases such as sickle-cell disease and thalassemia respectively.[16][17][18] Clinically important missense mutations generally change the properties of the coded amino acid residue between being basic, acidic, polar or non-polar, whereas nonsense mutations result in a stop codon.[9]:266

Mutations that disrupt the reading frame sequence by indels (insertions or deletions) of a non-multiple of 3 nucleotide bases are known as frameshift mutations. These mutations usually result in a completely different translation from the original, and are also very likely to cause a stop codon to be read, which truncates the creation of the protein.[19] These mutations may impair the function of the resulting protein, and are thus rare in in vivo protein-coding sequences. One reason inheritance of frameshift mutations is rare 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 death before the organism is viable.[20] Frameshift mutations may result in severe genetic diseases such as Tay-Sachs disease.[21]

Although most mutations that change protein sequences are harmful or neutral, some mutations have a beneficial effect on an organism.[22] These mutations may enable the mutant organism to withstand particular environmental stresses better than wild-type organisms, or reproduce more quickly. In these cases a mutation will tend to become more common in a population through natural selection.[23] Viruses that use RNA as their genetic material have rapid mutation rates,[24] which can be an advantage, since these viruses will evolve constantly and rapidly, and thus evade the defensive responses of e.g. the human immune system.[25] In large populations of asexually reproducing organisms, for example, E. coli, multiple beneficial mutations may co-occur. This phenomenon is called clonal interference and causes competition among the mutations.[26]

Degeneracy

Main article: Codon degeneracy

Degeneracy is the redundancy of the genetic code. The genetic code has redundancy but no ambiguity (see the codon tables below for the full correlation). For example, although codons GAA and GAG both specify glutamic acid (redundancy), neither of them specifies any other amino acid (no ambiguity). The codons encoding one amino acid may differ in any of their three positions. For example, the amino acid leucine is specified by YUR or CUN (UUA, UUG, CUU, CUC, CUA, or CUG) codons (difference in the first or third position indicated using IUPAC notation), while the amino acid serine is specified by UCN or AGY (UCA, UCG, UCC, UCU, AGU, or AGC) codons (difference in the first, second, or third position).[27]:521–522 A practical consequence of redundancy is that errors in the third position of the triplet codon cause only a silent mutation or an error that would not affect the protein because the hydrophilicity or hydrophobicity is maintained by equivalent substitution of amino acids; for example, a codon of NUN (where N = any nucleotide) tends to code for hydrophobic amino acids. NCN yields amino acid residues that are small in size and moderate in hydropathy; NAN encodes average size hydrophilic residues. The genetic code is so well-structured for hydropathy that a mathematical analysis (Singular Value Decomposition) of 12 variables (4 nucleotides x 3 positions) yields a remarkable correlation (C = 0.95) for predicting the hydropathy of the encoded amino acid directly from the triplet nucleotide sequence, without translation.[28][29] Note in the table, below, eight amino acids are not affected at all by mutations at the third position of the codon, whereas in the figure above, a mutation at the second position is likely to cause a radical change in the physicochemical properties of the encoded amino acid.

Grouping of codons by amino acid residue molar volume and hydropathy. A more detailed version is available.

Transfer of information via the genetic code

The genome of an organism is inscribed in DNA, or, in the case of some viruses, RNA. The portion of the genome that codes for a protein or an RNA is called a gene. Those genes that code for proteins are composed of tri-nucleotide units called codons, each coding for a single amino acid. Each nucleotide sub-unit consists of a phosphate, a deoxyribose sugar, and one of the four nitrogenous nucleobases. 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 the double-helix configuration, two strands of DNA are joined to each other by hydrogen bonds in an arrangement known as base pairing. These bonds almost always form between an adenine base on one strand and a thymine base on the other strand, or between a cytosine base on one strand and a guanine base on the other. This means that the number of A and T bases will be the same in a given double helix, as will the number of G and C bases.[27]:102–117 In RNA, thymine (T) is replaced by uracil (U), and the deoxyribose is substituted by ribose.[27]:127

Each protein-coding gene is transcribed into a molecule of the related RNA polymer. In prokaryotes, this RNA functions as messenger RNA or mRNA; in eukaryotes, the transcript needs to be processed to produce a mature mRNA. The mRNA is, in turn, translated on a ribosome into a chain of amino acids otherwise known as a polypeptide.[27]:Chp 12 The process of translation requires transfer RNAs which are covalently attached to a specific amino acid, guanosine triphosphate as an energy source, and a number of translation factors. tRNAs have anticodons complementary to the codons in an mRNA and can be covalently "charged" with specific amino acids at their 3' terminal CCA ends by enzymes known as aminoacyl tRNA synthetases, which have high specificity for both their cognate amino acid and tRNA. The high specificity of these enzymes is a major reason why the fidelity of protein translation is maintained.[27]:464–469

There are 4³ = 64 different codon combinations possible with a triplet codon of three nucleotides; all 64 codons are assigned to either an amino acid or a stop signal. 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. Therefore, this 9 base RNA sequence will be translated into an amino acid sequence that is three amino acids long.[27]:521–539 A given amino acid may be encoded by between one and six different codon sequences. A comparison may be made using bioinformatics tools wherein the codon is similar to a word, which is the standard data "chunk" and a nucleotide is similar to a bit, in that it is the smallest unit. This allows for powerful comparisons across species as well as within organisms.

The standard genetic code is shown in the following tables. Table 1 shows which amino acid each of the 64 codons specifies. Table 2 shows which 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).[27]:522

RNA codon table

nonpolar polar basic acidic (stop codon)
Standard genetic code
1st
base		 2nd base 3rd
base
U C A G
U UUU (Phe/F) Phenylalanine UCU (Ser/S) Serine UAU (Tyr/Y) Tyrosine UGU (Cys/C) Cysteine U
UUC UCC UAC UGC C
UUA (Leu/L) Leucine UCA UAA Stop (Ochre) UGA Stop (Opal) A
UUG UCG UAG Stop (Amber) UGG (Trp/W) Tryptophan     G
C CUU CCU (Pro/P) Proline CAU (His/H) Histidine CGU (Arg/R) Arginine U
CUC CCC CAC CGC C
CUA CCA CAA (Gln/Q) Glutamine CGA A
CUG CCG CAG CGG G
A AUU (Ile/I) Isoleucine ACU (Thr/T) Threonine         AAU (Asn/N) Asparagine AGU (Ser/S) Serine U
AUC ACC AAC AGC C
AUA ACA AAA (Lys/K) Lysine AGA (Arg/R) Arginine A
AUG[A] (Met/M) Methionine ACG AAG AGG G
G GUU (Val/V) Valine GCU (Ala/A) Alanine GAU (Asp/D) Aspartic acid GGU (Gly/G) Glycine U
GUC GCC GAC GGC C
GUA GCA GAA (Glu/E) Glutamic acid GGA A
GUG GCG GAG GGG G
A The 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.[30]
Inverse table (compressed using IUPAC notation)
Amino acid Codons Compressed Amino acid Codons Compressed
Ala/A GCU, GCC, GCA, GCG GCN Leu/L UUA, UUG, CUU, CUC, CUA, CUG YUR, CUN
Arg/R CGU, CGC, CGA, CGG, AGA, AGG CGN, MGR Lys/K AAA, AAG AAR
Asn/N AAU, AAC AAY Met/M AUG
Asp/D GAU, GAC GAY Phe/F UUU, UUC UUY
Cys/C UGU, UGC UGY Pro/P CCU, CCC, CCA, CCG CCN
Gln/Q CAA, CAG CAR Ser/S UCU, UCC, UCA, UCG, AGU, AGC UCN, AGY
Glu/E GAA, GAG GAR Thr/T ACU, ACC, ACA, ACG ACN
Gly/G GGU, GGC, GGA, GGG GGN Trp/W UGG
His/H CAU, CAC CAY Tyr/Y UAU, UAC UAY
Ile/I AUU, AUC, AUA AUH Val/V GUU, GUC, GUA, GUG GUN
START AUG STOP UAA, UGA, UAG UAR, URA

DNA codon table

Main article: DNA codon table

The DNA codon table is essentially identical to that for RNA, but with U replaced by T.


Codon frequency

The frequency of codons varies from species to species, and also intraspecifically. The following table is for the human genome.[31]

Human Genome

CodonAA Fraction Freq ‰ Number CodonAA Fraction Freq ‰ Number CodonAA Fraction Freq ‰ NumberCodonAA Fraction Freq ‰ Number
UUUF0.4617.6714298UCUS0.1915.2618711UAUY0.4412.2495699UGUC0.4610.6430311
UUCF0.5420.3824692UCCS0.2217.7718892UACY0.5615.3622407UGCC0.5412.6513028
UUAL0.087.7311881UCAS0.1512.2496448UAA*0.301.040285UGA*0.471.663237
UUGL0.1312.9525688UCGS0.054.4179419UAG*0.240.832109UGGW1.0013.2535595
CUUL0.1313.2536515CCUP0.2917.5713233CAUH0.4210.9441711CGUR0.084.5184609
CUCL0.2019.6796638CCCP0.3219.8804620CACH0.5815.1613713CGCR0.1810.4423516
CUAL0.077.2290751CCAP0.2816.9688038CAAQ0.2712.3501911CGAR0.116.2250760
CUGL0.4039.61611801CCGP0.116.9281570CAGQ0.7334.21391973CGGR0.2011.4464485
AUUI0.3616.0650473ACUT0.2513.1533609AAUN0.4717.0689701AGUS0.1512.1493429
AUCI0.4720.8846466ACCT0.3618.9768147AACN0.5319.1776603AGCS0.2419.5791383
AUAI0.177.5304565ACAT0.2815.1614523AAAK0.4324.4993621AGAR0.2112.2494682
AUGM1.0022.0896005ACGT0.116.1246105AAGK0.5731.91295568AGGR0.2112.0486463
GUUV0.1811.0448607GCUA0.2718.4750096GAUD0.4621.8885429GGUG0.1610.8437126
GUCV0.2414.5588138GCCA0.4027.71127679GACD0.5425.11020595GGCG0.3422.2903565
GUAV0.127.1287712GCAA0.2315.8643471GAAE0.4229.01177632GGAG0.2516.5669873
GUGV0.4628.11143534GCGA0.117.4299495GAGE0.5839.61609975GGGG0.2516.5669768

Variations to the standard genetic code

While slight variations on the standard code had been predicted earlier,[32] none were discovered until 1979, when researchers studying human mitochondrial genes discovered they used an alternative code.[33] Many slight variants have been discovered since then,[34] including various alternative mitochondrial codes,[35] and small variants such as translation of the codon UGA as tryptophan in Mycoplasma species, and translation of CUG as a serine rather than a leucine in yeasts of the "CTG clade" (Candida albicans is member of this group).[36][37][38] Because viruses must use the same genetic code as their hosts, modifications to the standard genetic code could interfere with the synthesis or functioning of viral proteins.[39] However, some viruses (such as totiviruses) have adapted to the genetic code modification of the host.[40] In bacteria and archaea, GUG and UUG are common start codons, but in rare cases, certain proteins may use alternative start codons not normally used by that species.[34]

In certain proteins, non-standard amino acids are substituted for standard stop codons, depending on associated signal sequences in the messenger RNA. For example, UGA can code for selenocysteine and UAG can code for pyrrolysine. Selenocysteine is now viewed as the 21st amino acid, and pyrrolysine is viewed as the 22nd.[34] Unlike selenocysteine, pyrrolysine encoded UAG is translated with the participation of a dedicated aminoacyl-tRNA synthetase.[41] Both selenocysteine and pyrrolysine may be present in the same organism.[42] Although the genetic code is normally fixed in an organism the achaeal prokaryote Acetohalobium arabaticum can expand its genetic code from 20 to 21 amino acids (by including pyrrolysine) under different conditions of growth.[43]

Despite these differences, all known naturally-occurring codes are very similar to each other, and the coding mechanism is the same for all organisms: three-base codons, tRNA, ribosomes, reading the code in the same direction and translating the code three letters at a time into sequences of amino acids.

Genetic code logo of the Globobulimina pseudospinescens mitochondrial genome. The logo shows the 64 codons from left to right, predicted alternatives in red (relative to the standard genetic code). Red line: stop codons. The height of each amino acid in the stack shows how often it is aligned to the codon in homologous protein domains. The stack height indicates the support for the prediction.

Predicting the genetic code

The genetic code used by a genome can be predicted by identifying the genes encoded on that genome, and comparing the codons on the DNA to the amino acids in homologous proteins in other genomes. The evolutionary conservation of protein sequences makes it possible to predict the amino acid translation for each codon as the one that is most often aligned to that codon. The program FACIL[44] allows the automated prediction of the genetic code, searching which amino acids in homologous protein domains are most often aligned to every codon. The resulting amino acid probabilities for each codon are displayed in a genetic code logo, that also shows the support for a stop codon.

Expanded genetic code

Main article: Expanded genetic code

Since 2001, 40 non-natural amino acids have been added into protein by creating a unique codon (recoding) and a corresponding transfer-RNA:aminoacyl – tRNA-synthetase pair to encode it with diverse physicochemical and biological properties in order to be used as a tool to exploring protein structure and function or to create novel or enhanced proteins.[45] [46]

H. Murakami and M. Sisido have extended some codons to have four and five bases. Steven A. Benner constructed a functional 65th (in vivo) codon.[47]

Origin

The origin of the genetic code is a part of the question of the origin of life. Under the main hypothesis for the origin of life, the RNA world hypothesis, any model for the emergence of genetic code is intimately related to a model of the transfer from ribozymes (RNA enzymes) to proteins as the principal enzymes in cells.

In line with the RNA world hypothesis, transfer RNA molecules appear to have evolved before modern aminoacyl-tRNA synthetases, so the latter cannot be part of the explanation of its patterns.[48]

There are three main ideas for the origin of the genetic code, and many models belong to either one of them or to a combination thereof:[49]

Many hypotheses stand as a combination of these three basic ideas, and run through four themes:[52]

Non-randomness

If amino acids were randomly assigned to triplet codons, then there would be 1.5 × 1084 possible genetic codes to choose from.[54]:163 This number is found by calculating how many ways there are to place 21 items (20 amino acids plus one stop) in 64 bins, wherein each item is used at least once.

In fact, the distribution of codon assignments in the genetic code is nonrandom.[66] In particular, the genetic code clusters certain amino acid assignments. For example:


Further models

Models based on signaling games combine elements of game theory, natural selection and information channels. Such models have been used to suggest that the first polypeptides were likely short and had some use other than enzymatic function. Game theoretic models have also suggested that the organization of RNA strings into cells may have been necessary to prevent "deceptive" use of the genetic code, i.e. preventing the ancient equivalent of viruses from overwhelming the RNA world.[70]

It has been suggested that robust hypothesis for the origin of genetic code should also address or predict the following gross features of the codon table:[71]

  1. absence of codons for D-amino acids
  2. secondary codon patterns for some amino acids
  3. confinement of synonymous positions to third position
  4. limitation to 20 amino acids instead of a number closer to 64
  5. relation of stop codon patterns to amino acid coding patterns

As an example for addressing the latter requirement, it has been suggested that the stop codons are such that they are most likely to terminate translation early in the case of a frame shift error.[72]

See also

References

  1. ↑ Turanov AA, Lobanov AV, Fomenko DE, Morrison HG, Sogin ML, Klobutcher LA, Hatfield DL, Gladyshev VN (Jan 2009). "Genetic code supports targeted insertion of two amino acids by one codon". Science 323 (5911): 259–61. doi:10.1126/science.1164748. PMC 3088105. PMID 19131629.
  2. ↑ Crick F (1988). "Chapter 8: The genetic code". What mad pursuit: a personal view of scientific discovery. New York: Basic Books. pp. 89–101. ISBN 0-465-09138-5.
  3. ↑ Nirenberg MW, Matthaei JH (Oct 1961). "The dependence of cell-free protein synthesis in E. coli upon naturally occurring or synthetic polyribonucleotides". Proceedings of the National Academy of Sciences of the United States of America 47 (10): 1588–602. Bibcode:1961PNAS...47.1588N. doi:10.1073/pnas.47.10.1588. PMC 223178. PMID 14479932.
  4. ↑ Gardner RS, Wahba AJ, Basilio C, Miller RS, Lengyel P, Speyer JF (Dec 1962). "Synthetic polynucleotides and the amino acid code. VII". Proceedings of the National Academy of Sciences of the United States of America 48 (12): 2087–94. Bibcode:1962PNAS...48.2087G. doi:10.1073/pnas.48.12.2087. PMC 221128. PMID 13946552.
  5. ↑ Wahba AJ, Gardner RS, Basilio C, Miller RS, Speyer JF, Lengyel P (Jan 1963). "Synthetic polynucleotides and the amino acid code. VIII". Proceedings of the National Academy of Sciences of the United States of America 49 (1): 116–22. Bibcode:1963PNAS...49..116W. doi:10.1073/pnas.49.1.116. PMC 300638. PMID 13998282.
  6. ↑ "The Nobel Prize in Physiology or Medicine 1959" (Press release). The Royal Swedish Academy of Science. 1959. Retrieved 2010-02-27. The Nobel Prize in Physiology or Medicine 1959 was awarded jointly to Severo Ochoa and Arthur Kornberg 'for their discovery of the mechanisms in the biological synthesis of ribonucleic acid and deoxyribonucleic acid'.
  7. ↑ Nirenberg M, Leder P, Bernfield M, Brimacombe R, Trupin J, Rottman F, O'Neal C (May 1965). "RNA codewords and protein synthesis, VII. On the general nature of the RNA code". Proceedings of the National Academy of Sciences of the United States of America 53 (5): 1161–8. Bibcode:1965PNAS...53.1161N. doi:10.1073/pnas.53.5.1161. PMC 301388. PMID 5330357.
  8. ↑ "The Nobel Prize in Physiology or Medicine 1968" (Press release). The Royal Swedish Academy of Science. 1968. Retrieved 2010-02-27. The Nobel Prize in Physiology or Medicine 1968 was awarded jointly to Robert W. Holley, Har Gobind Khorana and Marshall W. Nirenberg 'for their interpretation of the genetic code and its function in protein synthesis'.
  9. 1 2 Mulligan PK, King RC, Stansfield WD (2006). A dictionary of genetics. Oxford [Oxfordshire]: Oxford University Press. p. 608. ISBN 0-19-530761-5.
  10. ↑ Touriol C, Bornes S, Bonnal S, Audigier S, Prats H, Prats AC, Vagner S (2003). "Generation of protein isoform diversity by alternative initiation of translation at non-AUG codons". Biology of the Cell / Under the Auspices of the European Cell Biology Organization 95 (3–4): 169–78. doi:10.1016/S0248-4900(03)00033-9. PMID 12867081.
  11. ↑ Edgar B (Oct 2004). "The genome of bacteriophage T4: an archeological dig". Genetics 168 (2): 575–82. PMC 1448817. PMID 15514035.
  12. ↑ Maloy S (2003-11-29). "How nonsense mutations got their names". Microbial Genetics Course. San Diego State University. Retrieved 2010-03-10.
  13. ↑ References for the image are found in Wikimedia Commons page at: Commons:File:Notable mutations.svg#References.
  14. ↑ Griffiths AJ, Miller JH, Suzuki DT, Lewontin RC, et al., eds. (2000). "Spontaneous mutations". An Introduction to Genetic Analysis (7th ed.). New York: W. H. Freeman. ISBN 0-7167-3520-2.
  15. ↑ Freisinger E, Grollman AP, Miller H, Kisker C (Apr 2004). "Lesion (in)tolerance reveals insights into DNA replication fidelity". The EMBO Journal 23 (7): 1494–505. doi:10.1038/sj.emboj.7600158. PMC 391067. PMID 15057282.
  16. ↑ (Boillée 2006, p. 39)
  17. ↑ Chang JC, Kan YW (Jun 1979). "beta 0 thalassemia, a nonsense mutation in man". Proceedings of the National Academy of Sciences of the United States of America 76 (6): 2886–9. Bibcode:1979PNAS...76.2886C. doi:10.1073/pnas.76.6.2886. PMC 383714. PMID 88735.
  18. ↑ Boillée S, Vande Velde C, Cleveland DW (Oct 2006). "ALS: a disease of motor neurons and their nonneuronal neighbors". Neuron 52 (1): 39–59. doi:10.1016/j.neuron.2006.09.018. PMID 17015226.
  19. ↑ Isbrandt D, Hopwood JJ, von Figura K, Peters C (1996). "Two novel frameshift mutations causing premature stop codons in a patient with the severe form of Maroteaux-Lamy syndrome". Human Mutation 7 (4): 361–3. doi:10.1002/(SICI)1098-1004(1996)7:4<361::AID-HUMU12>3.0.CO;2-0. PMID 8723688.
  20. ↑ Crow JF (1993). "How much do we know about spontaneous human mutation rates?". Environmental and Molecular Mutagenesis 21 (2): 122–9. doi:10.1002/em.2850210205. PMID 8444142.
  21. ↑ Lewis R (2005). Human Genetics: Concepts and Applications (6th ed.). Boston, Mass: McGraw Hill. pp. 227–228. ISBN 0-07-111156-5.
  22. ↑ Sawyer SA, Parsch J, Zhang Z, Hartl DL (Apr 2007). "Prevalence of positive selection among nearly neutral amino acid replacements in Drosophila". Proceedings of the National Academy of Sciences of the United States of America 104 (16): 6504–10. Bibcode:2007PNAS..104.6504S. doi:10.1073/pnas.0701572104. PMC 1871816. PMID 17409186.
  23. ↑ Bridges KR (2002). "Malaria and the Red Cell". Harvard.
  24. ↑ Drake JW, Holland JJ (Nov 1999). "Mutation rates among RNA viruses". Proceedings of the National Academy of Sciences of the United States of America 96 (24): 13910–3. Bibcode:1999PNAS...9613910D. doi:10.1073/pnas.96.24.13910. PMC 24164. PMID 10570172.
  25. ↑ Holland J, Spindler K, Horodyski F, Grabau E, Nichol S, VandePol S (Mar 1982). "Rapid evolution of RNA genomes". Science 215 (4540): 1577–85. Bibcode:1982Sci...215.1577H. doi:10.1126/science.7041255. PMID 7041255.
  26. ↑ de Visser JA, Rozen DE (Apr 2006). "Clonal interference and the periodic selection of new beneficial mutations in Escherichia coli". Genetics 172 (4): 2093–100. doi:10.1534/genetics.105.052373. PMC 1456385. PMID 16489229.
  27. 1 2 3 4 5 6 7 Watson JD, Baker TA, Bell SP, Gann A, Levine M, Oosick R (2008). Molecular Biology of the Gene. San Francisco: Pearson/Benjamin Cummings. ISBN 0-8053-9592-X.
  28. ↑ Yang et al. (1990) in Michel-Beyerle, M. E., ed. Reaction centers of photosynthetic bacteria: Feldafing-II-Meeting 6. Berlin: Springer-Verlag. pp. 209–18. ISBN 3-540-53420-2.
  29. ↑ Füllen G, Youvan DC (1994). "Genetic Algorithms and Recursive Ensemble Mutagenesis in Protein Engineering". Complexity International 1.
  30. ↑ Nakamoto T (March 2009). "Evolution and the universality of the mechanism of initiation of protein synthesis". Gene 432 (1–2): 1–6. doi:10.1016/j.gene.2008.11.001. PMID 19056476.
  31. ↑ http://www.kazusa.or.jp/codon/cgi-bin/showcodon.cgi?species=9606&aa=1&style=N
  32. ↑ Crick FH, Orgel LE (1973). "Directed panspermia". Icarus 19 (3): 341–6, 344. Bibcode:1973Icar...19..341C. doi:10.1016/0019-1035(73)90110-3. It is a little surprising that organisms with somewhat different codes do not coexist. (Further discussion)
  33. ↑ Barrell BG, Bankier AT, Drouin J (1979). "A different genetic code in human mitochondria". Nature 282 (5735): 189–194. ()
  34. 1 2 3 Elzanowski A, Ostell J (2008-04-07). "The Genetic Codes". National Center for Biotechnology Information (NCBI). Retrieved 2010-03-10.
  35. ↑ Jukes TH, Osawa S (Dec 1990). "The genetic code in mitochondria and chloroplasts". Experientia 46 (11–12): 1117–26. doi:10.1007/BF01936921. PMID 2253709.
  36. ↑ Fitzpatrick DA, Logue ME, Stajich JE, Butler G (1 January 2006). "A fungal phylogeny based on 42 complete genomes derived from supertree and combined gene analysis". BMC Evolutionary Biology 6: 99. doi:10.1186/1471-2148-6-99. PMC 1679813. PMID 17121679.
  37. ↑ Santos MA, Tuite MF (May 1995). "The CUG codon is decoded in vivo as serine and not leucine in Candida albicans". Nucleic Acids Research 23 (9): 1481–6. doi:10.1093/nar/23.9.1481. PMC 306886. PMID 7784200.
  38. ↑ Butler G, Rasmussen MD, Lin MF, Santos MA, Sakthikumar S, Munro CA, Rheinbay E, Grabherr M, Forche A, Reedy JL, Agrafioti I, Arnaud MB, Bates S, Brown AJ, Brunke S, Costanzo MC, Fitzpatrick DA, de Groot PW, Harris D, Hoyer LL, Hube B, Klis FM, Kodira C, Lennard N, Logue ME, Martin R, Neiman AM, Nikolaou E, Quail MA, Quinn J, Santos MC, Schmitzberger FF, Sherlock G, Shah P, Silverstein KA, Skrzypek MS, Soll D, Staggs R, Stansfield I, Stumpf MP, Sudbery PE, Srikantha T, Zeng Q, Berman J, Berriman M, Heitman J, Gow NA, Lorenz MC, Birren BW, Kellis M, Cuomo CA (Jun 2009). "Evolution of pathogenicity and sexual reproduction in eight Candida genomes". Nature 459 (7247): 657–62. Bibcode:2009Natur.459..657B. doi:10.1038/nature08064. PMC 2834264. PMID 19465905.
  39. ↑ Witzany, G (2016) Crucial steps to life: From chemical reactions to code using agents. Biosystems 140: 49–57.
  40. ↑ Taylor DJ, Ballinger MJ, Bowman SM, Bruenn JA (2013). "Virus-host co-evolution under a modified nuclear genetic code". PeerJ 1: e50. doi:10.7717/peerj.50. PMC 3628385. PMID 23638388.
  41. ↑ Krzycki JA (Dec 2005). "The direct genetic encoding of pyrrolysine". Current Opinion in Microbiology 8 (6): 706–12. doi:10.1016/j.mib.2005.10.009. PMID 16256420.
  42. ↑ Zhang Y, Baranov PV, Atkins JF, Gladyshev VN (May 2005). "Pyrrolysine and selenocysteine use dissimilar decoding strategies". The Journal of Biological Chemistry 280 (21): 20740–51. doi:10.1074/jbc.M501458200. PMID 15788401.
  43. ↑ Prat L, Heinemann IU, Aerni HR, Rinehart J, O'Donoghue P, Söll D (Dec 2012). "Carbon source-dependent expansion of the genetic code in bacteria". Proceedings of the National Academy of Sciences of the United States of America 109 (51): 21070–5. Bibcode:2012PNAS..10921070P. doi:10.1073/pnas.1218613110. PMC 3529041. PMID 23185002.
  44. ↑ Dutilh BE, Jurgelenaite R, Szklarczyk R, van Hijum SA, Harhangi HR, Schmid M, de Wild B, Françoijs KJ, Stunnenberg HG, Strous M, Jetten MS, Op den Camp HJ, Huynen MA (Jul 2011). "FACIL: Fast and Accurate Genetic Code Inference and Logo". Bioinformatics 27 (14): 1929–33. doi:10.1093/bioinformatics/btr316. PMID 21653513.
  45. ↑ Xie J, Schultz PG (Dec 2005). "Adding amino acids to the genetic repertoire". Current Opinion in Chemical Biology 9 (6): 548–54. doi:10.1016/j.cbpa.2005.10.011. PMID 16260173.
  46. ↑ Wang Q, Parrish AR, Wang L (Mar 2009). "Expanding the genetic code for biological studies". Chemistry & Biology 16 (3): 323–36. doi:10.1016/j.chembiol.2009.03.001. PMC 2696486. PMID 19318213.
  47. ↑ Simon M (2005). Emergent computation: emphasizing bioinformatics. New York: AIP Press/Springer Science+Business Media. pp. 105–106. ISBN 0-387-22046-1.
  48. ↑ Ribas de Pouplana L, Turner RJ, Steer BA, Schimmel P (Sep 1998). "Genetic code origins: tRNAs older than their synthetases?". Proceedings of the National Academy of Sciences of the United States of America 95 (19): 11295–300. Bibcode:1998PNAS...9511295D. doi:10.1073/pnas.95.19.11295. PMC 21636. PMID 9736730.
  49. 1 2 Freeland SJ, Knight RD, Landweber LF, Hurst LD (Apr 2000). "Early fixation of an optimal genetic code". Molecular Biology and Evolution 17 (4): 511–18. PMID 10742043.
  50. ↑ Crick FH (Dec 1968). "The origin of the genetic code". Journal of Molecular Evolution 38 (3): 367–79. PMID 4887876.
  51. 1 2 Yarus M, Widmann JJ, Knight R (Nov 2009). "RNA-amino acid binding: a stereochemical era for the genetic code". Journal of Molecular Evolution 69 (5): 406–29. doi:10.1007/s00239-009-9270-1. PMID 19795157.
  52. ↑ Knight RD, Freeland SJ, Landweber LF (Jun 1999). "Selection, history and chemistry: the three faces of the genetic code". Trends in Biochemical Sciences 24 (6): 241–7. doi:10.1016/S0968-0004(99)01392-4. PMID 10366854.
  53. ↑ Knight RD, Landweber LF (Sep 1998). "Rhyme or reason: RNA-arginine interactions and the genetic code". Chemistry & Biology 5 (9): R215–20. doi:10.1016/S1074-5521(98)90001-1. PMID 9751648.
  54. 1 2 Yarus M (2010). Life from an RNA World: The Ancestor Within. Cambridge: Harvard University Press. p. 163. ISBN 0-674-05075-4.
  55. ↑ Sengupta, S., and P. G. Higgs (2015). Pathways of genetic code evolution in ancient and modern organisms. Journal of Molecular Evolution 80:229–243.
  56. ↑ Brooks DJ, Fresco JR, Lesk AM, Singh M (Oct 2002). "Evolution of amino acid frequencies in proteins over deep time: inferred order of introduction of amino acids into the genetic code". Molecular Biology and Evolution 19 (10): 1645–55. doi:10.1093/oxfordjournals.molbev.a003988. PMID 12270892.
  57. ↑ Amirnovin R (May 1997). "An analysis of the metabolic theory of the origin of the genetic code". Journal of Molecular Evolution 44 (5): 473–6. doi:10.1007/PL00006170. PMID 9115171.
  58. ↑ Ronneberg TA, Landweber LF, Freeland SJ (Dec 2000). "Testing a biosynthetic theory of the genetic code: fact or artifact?". Proceedings of the National Academy of Sciences of the United States of America 97 (25): 13690–5. Bibcode:2000PNAS...9713690R. doi:10.1073/pnas.250403097. PMC 17637. PMID 11087835.
  59. 1 2 Freeland SJ, Wu T, Keulmann N (Oct 2003). "The case for an error minimizing standard genetic code". Origins of Life and Evolution of the Biosphere 33 (4–5): 457–77. doi:10.1023/A:1025771327614. PMID 14604186.
  60. ↑ Baranov PV, Venin M, Provan G (2009). Gemmell NJ, ed. "Codon size reduction as the origin of the triplet genetic code". PLOS ONE 4 (5): e5708. Bibcode:2009PLoSO...4.5708B. doi:10.1371/journal.pone.0005708. PMC 2682656. PMID 19479032.
  61. ↑ Tlusty T (Nov 2007). "A model for the emergence of the genetic code as a transition in a noisy information channel". Journal of Theoretical Biology 249 (2): 331–42. doi:10.1016/j.jtbi.2007.07.029. PMID 17826800.
  62. ↑ Sonneborn TM (1965). Bryson V, Vogel H, eds. Evolving genes and proteins. New York: Academic Press. pp. 377–397.
  63. ↑ Tlusty T (Feb 2008). "Rate-distortion scenario for the emergence and evolution of noisy molecular codes". Physical Review Letters 100 (4): 048101. arXiv:1007.4149. Bibcode:2008PhRvL.100d8101T. doi:10.1103/PhysRevLett.100.048101. PMID 18352335.
  64. ↑ Sella G, Ardell DH (Sep 2006). "The coevolution of genes and genetic codes: Crick's frozen accident revisited". Journal of Molecular Evolution 63 (3): 297–313. doi:10.1007/s00239-004-0176-7. PMID 16838217.
  65. ↑ Tlusty T (Sep 2010). "A colorful origin for the genetic code: information theory, statistical mechanics and the emergence of molecular codes". Physics of Life Reviews 7 (3): 362–76. arXiv:1007.3906. Bibcode:2010PhLRv...7..362T. doi:10.1016/j.plrev.2010.06.002. PMID 20558115.
  66. 1 2 Freeland SJ, Hurst LD (Sep 1998). "The genetic code is one in a million". Journal of Molecular Evolution 47 (3): 238–48. doi:10.1007/PL00006381. PMID 9732450.
  67. ↑ Taylor FJ, Coates D (1989). "The code within the codons". Bio Systems 22 (3): 177–87. doi:10.1016/0303-2647(89)90059-2. PMID 2650752.
  68. ↑ Di Giulio M (Oct 1989). "The extension reached by the minimization of the polarity distances during the evolution of the genetic code". Journal of Molecular Evolution 29 (4): 288–93. doi:10.1007/BF02103616. PMID 2514270.
  69. ↑ Wong JT (Feb 1980). "Role of minimization of chemical distances between amino acids in the evolution of the genetic code". Proceedings of the National Academy of Sciences of the United States of America 77 (2): 1083–6. Bibcode:1980PNAS...77.1083W. doi:10.1073/pnas.77.2.1083. PMC 348428. PMID 6928661.
  70. ↑ Jee J, Sundstrom A, Massey SE, Mishra B (Nov 2013). "What can information-asymmetric games tell us about the context of Crick's 'frozen accident'?". Journal of the Royal Society, Interface / the Royal Society 10 (88): 20130614. doi:10.1098/rsif.2013.0614. PMC 3785830. PMID 23985735.
  71. ↑ Erives A (Aug 2011). "A model of proto-anti-codon RNA enzymes requiring L-amino acid homochirality". Journal of Molecular Evolution 73 (1–2): 10–22. doi:10.1007/s00239-011-9453-4. PMC 3223571. PMID 21779963.
  72. ↑ Itzkovitz S, Alon U (2007). "The genetic code is nearly optimal for allowing additional information within protein-coding sequences". Genome research 17 (4): 405–412. doi:10.1101/gr.5987307.

Further reading

External links

Wikimedia Commons has media related to Genetic code.

This article is issued from Wikipedia - version of the Saturday, April 30, 2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.