The genetic code is the set of rules used by living cells to translate information encoded within genetic material (DNA or mRNA sequences) into proteins. Translation is accomplished by the ribosome, which links amino acids in an order specified by messenger RNA (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, a three-nucleotide codon in a nucleic acid sequence specifies a single amino acid. The vast majority of genes are encoded with a single scheme (see the RNA codon table). That scheme is often referred to as the canonical or standard genetic code, or simply the genetic code, though variant codes (such as in human mitochondria) exist.
While the "genetic code" determines a protein's amino acid sequence, other genomic regions determine when and where these proteins are produced according to various "gene regulatory codes".
Efforts to understand how proteins are encoded began after DNA's structure 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, which would allow a maximum of 43 = 64 amino acids.
The Crick, Brenner, Barnett and Watts-Tobin experiment first demonstrated that codons consist of three DNA bases. Marshall Nirenberg and Heinrich J. Matthaei were the first to reveal the nature of a codon in 1961.
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. 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 and that the poly-cytosine RNA sequence (CCCCC...) coded for the polypeptide poly-proline. Therefore, the codon AAA specified the amino acid lysine, and the codon CCC specified the amino acid proline. Using various 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 Ochoa's earlier studies, yielding the latter the Nobel Prize in Physiology or Medicine in 1959 for work on the enzymology of RNA synthesis.
Extending this work, Nirenberg and Philip Leder revealed the code's triplet nature and deciphered its codons. 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. Khorana, Holley and Nirenberg received the 1968 Nobel for their work.
The three stop codons were named by discoverers Richard Epstein and Charles Steinberg. "Amber" was named after their friend Harris Bernstein, whose last name means "amber" in German. The other two stop codons were named "ochre" and "opal" in order to keep the "color names" theme.
In a broad academic audience, the concept of the evolution of the genetic code from the original and ambiguous genetic code to a well-defined ("frozen") code with the repertoire of 20 (+2) canonical amino acids is widely accepted. However, there are different opinions, concepts, approaches and ideas, which is the best way to change it experimentally. Even models are proposed that predict "entry points" for synthetic amino acid invasion of the 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. 
In 2015 N. Budisa, D. Söll and co-workers reported the full substitution of all 20,899 tryptophan residues (UGG codons) with unnatural thienopyrrole-alanine in the genetic code of the bacterium Escherichia coli.
In 2017, researchers in South Korea reported that they had engineered a mouse with an extended genetic code that can produce proteins with unnatural amino acids.
A reading frame is defined by the initial triplet of nucleotides from which translation starts. It sets the frame for a run of successive, non-overlapping codons, which is known as an "open reading frame" (ORF). For example, the string 5'-AAATGAACG-3' (see figure), if read from the first position, contains the codons AAA, TGA, and ACG ; if read from the second position, it contains the codons AAT and GAA ; and if read from the third position, it contains the codons ATG and AAC. Every sequence can, thus, be read in its 5' → 3' direction in three reading frames, each producing a possibly distinct amino acid sequence: in the given example, Lys (K)-Trp (W)-Thr (T), Asn (N)-Glu (E), or Met (M)-Asn (N), respectively (when translating with the vertebrate mitochondrial code). When DNA is double-stranded, six possible reading frames are defined, three in the forward orientation on one strand and three reverse on the opposite strand.:330 Protein-coding frames are defined by a start codon, usually the first AUG (ATG) codon in the RNA (DNA) sequence.
Translation starts with a chain-initiation codon or start codon. The start 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.
The three stop codons have names: UAG is amber, UGA is opal (sometimes also called umber), and UAA is ochre. Stop codons are also called "termination" or "nonsense" codons. They signal release of the nascent polypeptide from the ribosome because no cognate tRNA has anticodons complementary to these stop signals, allowing a release factor to bind to the ribosome instead.
During the process of DNA replication, errors occasionally occur in the polymerization of the second strand. These errors, mutations, can affect an organism's phenotype, especially if they occur within the protein coding sequence of a gene. Error rates are typically 1 error in every 10–100 million bases—due to the "proofreading" ability of DNA polymerases.
Missense mutations and nonsense mutations are examples of point mutations that can cause genetic diseases such as sickle-cell disease and thalassemia respectively. Clinically important missense mutations generally change the properties of the coded amino acid residue among basic, acidic, polar or non-polar states, whereas nonsense mutations result in a stop codon.: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 likely cause a stop codon to be read, which truncates the protein. These mutations may impair the protein's function 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 becomes viable. Frameshift mutations may result in severe genetic diseases such as Tay–Sachs disease.
Although most mutations that change protein sequences are harmful or neutral, some mutations have benefits. 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. Viruses that use RNA as their genetic material have rapid mutation rates, which can be an advantage, since these viruses thereby evolve rapidly, and thus evade the immune system defensive responses. 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.
Degeneracy is the redundancy of the genetic code. This term was given by Bernfield and Nirenberg. 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 specifies another 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).:102–117 :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. 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. Nevertheless, changes in the first position of the codons are more important than changes in the second position on a global scale. The reason may be that charge reversal (from a positive to a negative charge or vice versa) can only occur upon mutations in the first position, but never upon changes in the second position of a codon. Such charge reversal may have dramatic consequences for the structure or function of a protein. This aspect may have been largely underestimated by previous studies.
The frequency of codons, also known as codon usage bias, can vary from species to species with functional implications for the control of translation. The following codon usage table is for the human genome.
Human genome codon frequency table
A Amino acid. B Fraction of each codon among all those specifying a given amino acid. C Frequency among 40,662,582 codons of 93,487 coding sequences. D Number.
|Amino acids biochemical properties||nonpolar||polar||basic||acidic||Termination: stop codon|
|U||UUU||(Phe/F) Phenylalanine||UCU||(Ser/S) Serine||UAU||(Tyr/Y) Tyrosine||UGU||(Cys/C) Cysteine||U|
|UUA||(Leu/L) Leucine||UCA||UAA||Stop (Ochre) [B]||UGA||Stop (Opal) [B]||A|
|UUG||UCG||UAG||Stop (Amber) [B]||UGG||(Trp/W) Tryptophan||G|
|C||CUU||CCU||(Pro/P) Proline||CAU||(His/H) Histidine||CGU||(Arg/R) Arginine||U|
|A||AUU||(Ile/I) Isoleucine||ACU||(Thr/T) Threonine||AAU||(Asn/N) Asparagine||AGU||(Ser/S) Serine||U|
|AUA||ACA||AAA||(Lys/K) Lysine||AGA||(Arg/R) Arginine||A|
|G||GUU||(Val/V) Valine||GCU||(Ala/A) Alanine||GAU||(Asp/D) Aspartic acid||GGU||(Gly/G) Glycine||U|
|GUA||GCA||GAA||(Glu/E) Glutamic acid||GGA||A|
|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|
In some 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 became to be seen as the 21st amino acid, and pyrrolysine as the 22nd. Unlike selenocysteine, pyrrolysine-encoded UAG is translated with the participation of a dedicated aminoacyl-tRNA synthetase. Both selenocysteine and pyrrolysine may be present in the same organism. 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.
Variations on the standard code were predicted in the 1970s. The first was discovered in 1979, by researchers studying human mitochondrial genes. Many slight variants were discovered thereafter, including various alternative mitochondrial codes. These minor variants for example involve translation of the codon UGA as tryptophan in Mycoplasma species, and translation of CUG as a serine rather than leucine in yeasts of the "CTG clade" (such as Candida albicans). Because viruses must use the same genetic code as their hosts, modifications to the standard genetic code could interfere with viral protein synthesis or functioning. However, viruses such as totiviruses have adapted to the host's genetic code modification. In bacteria and archaea, GUG and UUG are common start codons. In rare cases, certain proteins may use alternative start codons. Surprisingly, variations in the interpretation of the genetic code exist also in human nuclear-encoded genes: In 2016, researchers studying the translation of malate dehydrogenase found that in about 4% of the mRNAs encoding this enzyme the stop codon is naturally used to encode the amino acids tryptophan and arginine. This type of recoding is induced by a high-readthrough stop codon context and it is referred to as functional translational readthrough.
Variant genetic codes used by an organism can be inferred by identifying highly conserved genes encoded in that genome, and comparing its codon usage to the amino acids in homologous proteins of other organisms. For example, the program FACIL infers a genetic code by 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.
Despite these differences, all known naturally occurring codes are very similar. The coding mechanism is the same for all organisms: three-base codons, tRNA, ribosomes, single direction reading and translating single codons into single amino acids.
List of alternative codons
The genetic code is a key part of the story of life, according to which self-replicating RNA molecules preceded life as we know it. The main hypothesis for life's origin is 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.
A hypothetical randomly evolved genetic code further motivates a biochemical or evolutionary model for its origin. If amino acids were randomly assigned to triplet codons, there would be 1.5 × 1084 possible genetic codes.:163 This number is found by calculating the number of ways that 21 items (20 amino acids plus one stop) can be placed in 64 bins, wherein each item is used at least once. However, the distribution of codon assignments in the genetic code is nonrandom. In particular, the genetic code clusters certain amino acid assignments.
Amino acids that share the same biosynthetic pathway tend to have the same first base in their codons. This could be an evolutionary relic of an early, simpler genetic code with fewer amino acids that later evolved to code a larger set of amino acids. It could also reflect steric and chemical properties that had another effect on the codon during its evolution. Amino acids with similar physical properties also tend to have similar codons, reducing the problems caused by point mutations and mistranslations.
Given the non-random genetic triplet coding scheme, a tenable hypothesis for the origin of genetic code could address multiple aspects of the codon table, such as absence of codons for D-amino acids, secondary codon patterns for some amino acids, confinement of synonymous positions to third position, the small set of only 20 amino acids (instead of a number approaching 64), and the relation of stop codon patterns to amino acid coding patterns.
Three main hypotheses address the origin of the genetic code. Many models belong to one of them or to a hybrid:
Hypotheses have addressed a variety of scenarios:
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'.
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'.
It is a little surprising that organisms with somewhat different codes do not coexist.(Further discussion)
Amino acids are organic compounds containing amine (-NH2) and carboxyl (-COOH) functional groups, along with a side chain (R group) specific to each amino acid. The key elements of an amino acid are carbon (C), hydrogen (H), oxygen (O), and nitrogen (N), although other elements are found in the side chains of certain amino acids. About 500 naturally occurring amino acids are known (though only 20 appear in the genetic code) and can be classified in many ways. They can be classified according to the core structural functional groups' locations as alpha- (α-), beta- (β-), gamma- (γ-) or delta- (δ-) amino acids; other categories relate to polarity, pH level, and side chain group type (aliphatic, acyclic, aromatic, containing hydroxyl or sulfur, etc.). In the form of proteins, amino acid residues form the second-largest component (water is the largest) of human muscles and other tissues. Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis.
In biochemistry, amino acids having both the amine and the carboxylic acid groups attached to the first (alpha-) carbon atom have particular importance. They are known as 2-, alpha-, or α-amino acids (generic formula H2NCHRCOOH in most cases, where R is an organic substituent known as a "side chain"); often the term "amino acid" is used to refer specifically to these. They include the 22 proteinogenic ("protein-building") amino acids, which combine into peptide chains ("polypeptides") to form the building-blocks of a vast array of proteins. These are all L-stereoisomers ("left-handed" isomers), although a few D-amino acids ("right-handed") occur in bacterial envelopes, as a neuromodulator (D-serine), and in some antibiotics.Twenty of the proteinogenic amino acids are encoded directly by triplet codons in the genetic code and are known as "standard" amino acids. The other two ("non-standard" or "non-canonical") are selenocysteine (present in many prokaryotes as well as most eukaryotes, but not coded directly by DNA), and pyrrolysine (found only in some archea and one bacterium). Pyrrolysine and selenocysteine are encoded via variant codons; for example, selenocysteine is encoded by stop codon and SECIS element. N-formylmethionine (which is often the initial amino acid of proteins in bacteria, mitochondria, and chloroplasts) is generally considered as a form of methionine rather than as a separate proteinogenic amino acid. Codon–tRNA combinations not found in nature can also be used to "expand" the genetic code and form novel proteins known as alloproteins incorporating non-proteinogenic amino acids.Many important proteinogenic and non-proteinogenic amino acids have biological functions. For example, in the human brain, glutamate (standard glutamic acid) and gamma-amino-butyric acid ("GABA", non-standard gamma-amino acid) are, respectively, the main excitatory and inhibitory neurotransmitters. Hydroxyproline, a major component of the connective tissue collagen, is synthesised from proline. Glycine is a biosynthetic precursor to porphyrins used in red blood cells. Carnitine is used in lipid transport.
Nine proteinogenic amino acids are called "essential" for humans because they cannot be produced from other compounds by the human body and so must be taken in as food. Others may be conditionally essential for certain ages or medical conditions. Essential amino acids may also differ between species.Because of their biological significance, amino acids are important in nutrition and are commonly used in nutritional supplements, fertilizers, feed, and food technology. Industrial uses include the production of drugs, biodegradable plastics, and chiral catalysts.Aminoacyl tRNA synthetase
An aminoacyl-tRNA synthetase (aaRS or ARS), also called tRNA-ligase, is an enzyme that attaches the appropriate amino acid onto its tRNA. It does so by catalyzing the esterification of a specific cognate amino acid or its precursor to one of all its compatible cognate tRNAs to form an aminoacyl-tRNA. In humans, the 20 different types of aa-tRNA are made by the 20 different aminoacyl-tRNA synthetases, one for each amino acid of the genetic code.
This is sometimes called "charging" or "loading" the tRNA with the amino acid. Once the tRNA is charged, a ribosome can transfer the amino acid from the tRNA onto a growing peptide, according to the genetic code. Aminoacyl tRNA therefore plays an important role in RNA translation, the expression of genes to create proteins.
As genetic efficiency evolved in higher organisms, 13 new domains with no obvious association with the catalytic activity of aaRSs genes have been added.Code
In communications and information processing, code is a system of rules to convert information—such as a letter, word, sound, image, or gesture—into another form or representation, sometimes shortened or secret, for communication through a communication channel or storage in a storage medium. An early example is the invention of language, which enabled a person, through speech, to communicate what he or she saw, heard, felt, or thought to others. But speech limits the range of communication to the distance a voice can carry, and limits the audience to those present when the speech is uttered. The invention of writing, which converted spoken language into visual symbols, extended the range of communication across space and time.
The process of encoding converts information from a source into symbols for communication or storage. Decoding is the reverse process, converting code symbols back into a form that the recipient understands, such as English or Spanish.
One reason for coding is to enable communication in places where ordinary plain language, spoken or written, is difficult or impossible. For example, semaphore, where the configuration of flags held by a signaler or the arms of a semaphore tower encodes parts of the message, typically individual letters and numbers. Another person standing a great distance away can interpret the flags and reproduce the words sent.Common descent
Common descent describes how, in evolutionary biology, a group of organisms share a most recent common ancestor. There is "massive" evidence of common descent of all life on Earth from the last universal common ancestor (LUCA). In July 2016, scientists reported identifying a set of 355 genes from the LUCA, by comparing the genomes of the three domains of life, archaea, bacteria, and eukaryotes.Common ancestry between organisms of different species arises during speciation, in which new species are established from a single ancestral population. Organisms which share a more-recent common ancestor are more closely related. The most recent common ancestor of all currently living organisms is the last universal ancestor, which lived about 3.9 billion years ago. The two earliest evidences for life on Earth are graphite found to be biogenic in 3.7 billion-year-old metasedimentary rocks discovered in western Greenland and microbial mat fossils found in 3.48 billion-year-old sandstone discovered in Western Australia. All currently living organisms on Earth share a common genetic heritage, though the suggestion of substantial horizontal gene transfer during early evolution has led to questions about the monophyly (single ancestry) of life. 6,331 groups of genes common to all living animals have been identified; these may have arisen from a single common ancestor that lived 650 million years ago in the Precambrian.Universal common descent through an evolutionary process was first proposed by the British naturalist Charles Darwin in the concluding sentence of his 1859 book On the Origin of Species:
There is grandeur in this view of life, with its several powers, having been originally breathed into a few forms or into one; and that, whilst this planet has gone cycling on according to the fixed law of gravity, from so simple a beginning endless forms most beautiful and most wonderful have been, and are being, evolved.Crick, Brenner et al. experiment
The Crick, Brenner et al. experiment (1961) was a scientific experiment performed by Francis Crick, Sydney Brenner, Leslie Barnett and R.J. Watts-Tobin. This study demonstrated that the genetic code is made up of a series of three base pair codons which code for individual amino acids. The experiment also elucidated the nature of gene expression and frame-shift mutations.DNA codon table
The standard genetic code is traditionally represented as an RNA codon table because, when proteins are made in a cell by ribosomes, it is mRNA that directs protein synthesis. The mRNA sequence is determined by the sequence of genomic DNA. With the rise of computational biology and genomics, most genes are now discovered at the DNA level, so a DNA codon table is becoming increasingly useful. In this context, the standard genetic code is referred as to translation table 1.The DNA codons in such tables occur on the sense DNA strand and are arranged in a 5' → 3' direction. There is the existence of symmetrical and asymmetrical characteristics in genetic codes.
A The codon ATG both codes for methionine and serves as an initiation site: the first ATG in an mRNA's coding region is where translation into protein begins.
B ^ ^ ^ The historical basis for designating the stop codons as amber, ochre and opal is described in an autobiography by Sydney Brenner and in a historical article by Bob Edgar.Expanded genetic code
An expanded genetic code is an artificially modified genetic code in which one or more specific codons have been re-allocated to encode an amino acid that is not among the 20 common naturally-encoded proteinogenic amino acids.The key prerequisites to expand the genetic code are:
the non-standard amino acid to encode,
an unused codon to adopt,
a tRNA that recognises this codon, and
a tRNA synthetase that recognises only that tRNA and only the non-standard amino acid.Expanding the genetic code is an area of research of synthetic biology, an applied biological discipline whose goal is to engineer living systems for useful purposes. The genetic code expansion enriches the repertoire of useful tools available to science.Loxodes
Loxodes is a genus of karyorelictean ciliates, belonging to family Loxodidae. It is the only known karyorelictean ciliate that lives in freshwater habitats.
The term Loxodes derives from the ancient greek λοξός (loxós), meaning "oblique, tilted".Marshall Warren Nirenberg
Marshall Warren Nirenberg (April 10, 1927 – January 15, 2010) was a Jewish American biochemist and geneticist. He shared a Nobel Prize in Physiology or Medicine in 1968 with Har Gobind Khorana and Robert W. Holley for "breaking the genetic code" and describing how it operates in protein synthesis. In the same year, together with Har Gobind Khorana, he was awarded the Louisa Gross Horwitz Prize from Columbia University.Nirenberg and Leder experiment
The Nirenberg and Leder experiment was a scientific experiment performed in 1964 by Marshall W. Nirenberg and Philip Leder. The experiment elucidated the triplet nature of the genetic code and allowed the remaining ambiguous codons in the genetic code to be deciphered.
In this experiment, using a ribosome binding assay, various combinations of mRNA were passed through a filter which contained ribosomes. Unique triplets promoted the binding of specific tRNAs to the ribosome. By associating the tRNA with its specific amino acid, it was possible to determine the triplet mRNA sequence that coded for each amino acid.Nirenberg and Matthaei experiment
The Nirenberg and Matthaei experiment was a scientific experiment performed on May 15, 1961, by Marshall W. Nirenberg and his post doctoral fellow, J. Heinrich Matthaei. The experiment deciphered the first of the 64 triplet codons in the genetic code by using nucleic acid homopolymers to translate specific amino acids.
In the experiment, an extract from bacterial cells that could make protein even when no intact living cells were present was prepared. Adding an artificial form of RNA consisting entirely of uracil-containing nucleotides, the polyuridylic acid (or poly-U), to this extract caused it to make a protein composed entirely of the amino acid phenylalanine. This experiment cracked the first codon of the genetic code and showed that RNA controlled the production of specific types of protein.Nucleotide
Nucleotides are organic molecules that serve as the monomer units for forming the nucleic acid polymers deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules within all life-forms on Earth. Nucleotides are the building blocks of nucleic acids; they are composed of three subunit molecules: a nitrogenous base, a five-carbon sugar (ribose or deoxyribose), and at least one phosphate group.
A nucleoside is a nitrogenous base and a 5-carbon sugar. Thus a nucleoside plus a phosphate group yields a nucleotide.
Nucleotides also play a central role in metabolism at a fundamental, cellular level. They carry packets of chemical energy—in the form of the nucleoside triphosphates Adenosine triphosphate (ATP), Guanosine triphosphate (GTP), Cytidine triphosphate (CTP) and Uridine triphosphate (UTP)—throughout the cell to the many cellular functions that demand energy, which include: synthesizing amino acids, proteins and cell membranes and parts, moving the cell and moving cell parts (both internally and intercellularly), dividing the cell, etc. In addition, nucleotides participate in cell signaling (cyclic guanosine monophosphate or cGMP and cyclic adenosine monophosphate or cAMP), and are incorporated into important cofactors of enzymatic reactions (e.g. coenzyme A, FAD, FMN, NAD, and NADP+).
In experimental biochemistry, nucleotides can be radiolabeled with radionuclides to yield radionucleotides.Protein
Proteins are large biomolecules, or macromolecules, consisting of one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific three-dimensional structure that determines its activity.
A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides, or sometimes oligopeptides. The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid residues in a protein is defined by the sequence of a gene, which is encoded in the genetic code. In general, the genetic code specifies 20 standard amino acids; however, in certain organisms the genetic code can include selenocysteine and—in certain archaea—pyrrolysine. Shortly after or even during synthesis, the residues in a protein are often chemically modified by post-translational modification, which alters the physical and chemical properties, folding, stability, activity, and ultimately, the function of the proteins. Sometimes proteins have non-peptide groups attached, which can be called prosthetic groups or cofactors. Proteins can also work together to achieve a particular function, and they often associate to form stable protein complexes.
Once formed, proteins only exist for a certain period and are then degraded and recycled by the cell's machinery through the process of protein turnover. A protein's lifespan is measured in terms of its half-life and covers a wide range. They can exist for minutes or years with an average lifespan of 1–2 days in mammalian cells. Abnormal or misfolded proteins are degraded more rapidly either due to being targeted for destruction or due to being unstable.
Like other biological macromolecules such as polysaccharides and nucleic acids, proteins are essential parts of organisms and participate in virtually every process within cells. Many proteins are enzymes that catalyse biochemical reactions and are vital to metabolism. Proteins also have structural or mechanical functions, such as actin and myosin in muscle and the proteins in the cytoskeleton, which form a system of scaffolding that maintains cell shape. Other proteins are important in cell signaling, immune responses, cell adhesion, and the cell cycle. In animals, proteins are needed in the diet to provide the essential amino acids that cannot be synthesized. Digestion breaks the proteins down for use in the metabolism.
Proteins may be purified from other cellular components using a variety of techniques such as ultracentrifugation, precipitation, electrophoresis, and chromatography; the advent of genetic engineering has made possible a number of methods to facilitate purification. Methods commonly used to study protein structure and function include immunohistochemistry, site-directed mutagenesis, X-ray crystallography, nuclear magnetic resonance and mass spectrometry.Reading frame
In molecular biology, a reading frame is a way of dividing the sequence of nucleotides in a nucleic acid (DNA or RNA) molecule into a set of consecutive, non-overlapping triplets. Where these triplets equate to amino acids or stop signals during translation, they are called codons.
A single strand of a nucleic acid molecule has a phosphoryl end, called the 5′-end, and a hydroxyl or 3′-end. These define the 5'→3' direction. There are three reading frames that can be read in this 5'→3' direction, each beginning from a different nucleotide in a triplet. In a double stranded nucleic acid, an additional three reading frames may be read from the other, complementary strand in the 5'→3' direction along this strand. As the two strands of a double-stranded nucleic acid molecule are antiparallel, the 5'→3' direction on the second strand corresponds to the 3'→5' direction along the first strand.In general, at the most, one reading frame in a given section of a nucleic acid, is biologically relevant (open reading frame). Some viral transcripts can be translated using multiple, overlapping reading frames. There is one known example of overlapping reading frames in mammalian mitochondrial DNA: coding portions of genes for 2 subunits of ATPase overlap.Start codon
The start codon is the first codon of a messenger RNA (mRNA) transcript translated by a ribosome. The start codon always codes for methionine in eukaryotes and a modified Met (fMet) in prokaryotes. The most common start codon is AUG.
The start codon is often preceded by a 5' untranslated region (5' UTR). In prokaryotes this includes the ribosome binding site.Stop codon
In the genetic code, a stop codon (or termination codon) is a nucleotide triplet within messenger RNA that signals a termination of translation into proteins. Proteins are based on polypeptides, which are unique sequences of amino acids. Most codons in messenger RNA (from DNA) correspond to the addition of an amino acid to a growing polypeptide chain, which may ultimately become a protein. Stop codons signal the termination of this process by binding release factors, which cause the ribosomal subunits to disassociate, releasing the amino acid chain. While start codons need nearby sequences or initiation factors to start translation, a stop codon alone is sufficient to initiate termination.Transfer RNA
A transfer RNA (abbreviated tRNA and formerly referred to as sRNA, for soluble RNA) is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length, that serves as the physical link between the mRNA and the amino acid sequence of proteins. tRNA does this by carrying an amino acid to the protein synthetic machinery of a cell (ribosome) as directed by a 3-nucleotide sequence (codon) in a messenger RNA (mRNA). As such, tRNAs are a necessary component of translation, the biological synthesis of new proteins in accordance with the genetic code.Translation (biology)
In molecular biology and genetics, translation is the process in which ribosomes in the cytoplasm or ER synthesize proteins after the process of transcription of DNA to RNA in the cell's nucleus. The entire process is called gene expression.
In translation, messenger RNA (mRNA) is not decoded in a ribosome to produce a specific amino acid chain, or polypeptide. The polypeptide later folds into an active protein and performs its functions in the cell. The ribosome facilitates decoding by inducing the binding of complementary tRNA anticodon sequences to mRNA codons. The tRNAs carry specific amino acids that are chained together into a polypeptide as the mRNA passes through and is "read" by the ribosome.
Translation proceeds in three phases:
Initiation: The ribosome assembles around the target mRNA. The first tRNA is attached at the start codon.
Elongation: The tRNA transfers an amino acid to the tRNA corresponding to the next codon. The ribosome then moves (translocates) to the next mRNA codon to continue the process, creating an amino acid chain.
Termination: When a stop codon is reached, the ribosome releases the polypeptide.In prokaryotes (bacteria), translation occurs in the cytosol, where the medium and small subunits of the ribosome bind to the tRNA. In eukaryotes, translation occurs in the cytosol or across the membrane of the endoplasmic reticulum in a process called co-translational translocation. In co-translational translocation, the entire ribosome/mRNA complex binds to the outer membrane of the rough endoplasmic reticulum (ER) and the new protein is synthesized and released into the ER; the newly created polypeptide can be stored inside the ER for future vesicle transport and secretion outside the cell, or immediately secreted.
Many types of transcribed RNA, such as transfer RNA, ribosomal RNA, and small nuclear RNA, do not undergo translation into proteins.
A number of antibiotics act by inhibiting translation. These include clindamycin, anisomycin, cycloheximide, chloramphenicol, tetracycline, streptomycin, erythromycin, and puromycin. Prokaryotic ribosomes have a different structure from that of eukaryotic ribosomes, and thus antibiotics can specifically target bacterial infections without any harm to a eukaryotic host's cells.Xenobiology
Xenobiology (XB) is a subfield of synthetic biology, the study of synthesizing and manipulating biological devices and systems. Xenobiology derives from the Greek word xenos, which means "stranger, guest". Xenobiology describes a form of biology that is not (yet) familiar to science and is not found in nature. In practice it describes novel biological systems and biochemistries that differ from the canonical DNA-RNA-20 amino acid system (see central dogma of molecular biology). For example, instead of DNA or RNA, XB explores nucleic acid analogues, termed Xeno Nucleic Acid (XNA) as information carriers. It also focuses on an expanded genetic code and the incorporation of non-proteinogenic amino acids into proteins.