All organisms' DNA contain regulatory sequences, intergenic segments, chomosomal structural areas, which can contribute greatly to phenotype but operate using a distinct sets of rules which may or may not be as straightforward as the well-defined codon-to-amino acid paradigm which underlies the genetic code.
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 because 3 is the smallest n such that 4 n is at least The fact that codons did consist of three DNA bases was first demonstrated in the Crick, Brenner et al. The first elucidation of a codon was done by Marshall Nirenberg and Heinrich J.
Matthaei in at the National Institutes of Health. They thereby deduced from this poly-phenylalanine that the codon UUU specified the amino-acid phenylalanine. Extending this work, Nirenberg and his coworkers were able to determine the nucleotide makeup of each codon. In order to determine the order of the sequence, trinucleotides were bound to ribosomes and radioactively labeled aminoacyl-tRNA was used to determine which amino acid corresponded to the codon.
Nirenberg's group was able to determine the sequences of 54 out of 64 codons. Subsequent work by Har Gobind Khorana identified the rest of the code, and shortly thereafter Robert W. Holley determined the structure of transfer RNA , the adapter molecule that facilitates translation. The portion of the genome that codes for a protein or an RNA is referred to as 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 , deoxyribose sugar and one of the 4 nitrogenous nucleotide bases. 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 on the other strand and between a cytosine base on one strand and a guanine base on the other. This means that the number of A and T residues will be the same in a given double helix as will the number of G and C residues.
This in turn is translated on the ribosome into an amino acid chain or polypeptide. 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.
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 reason why the fidelity of protein translation is maintained. In reality, all 64 codons of the standard genetic code are assigned for either amino acids or stop signals during translation.
This RNA sequence will be translated into an amino acid sequence, three amino acids long. A comparison may be made with computer science, where the codon is the equivalent of a word, which is the standard "chunk" for handling data like one amino acid of a protein , and a nucleotide for a bit. 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.
Note that a codon is defined by the initial nucleotide from which translation starts. 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 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 a non-multiple of 3 nucleotide bases are known 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. In 9 groups of codons, the nucleotides at the first two positions are sufficient to specify a unique amino acid, and any nucleotide abbreviated N at the third position encodes that same amino acid. These comprise 9 codon "families". An example is ACN encoding threonine. There are 13 codon "pairs", in which the nucleotides at the first two positions are sufficient to specify two amino acids.
A purine R nucleotide at the third position specifies one amino acid, whereas a pyrimidine Y nucleotide at the third position specifies the other amino acid. The UAR codons specifying termination of translation were counted as a codon pair. The codons for leucine and arginine, with both a codon family and a codon pair, provide the few examples of degeneracy in the first position of the codon. Degeneracy at the second position of the codon is not observed for codons encoding amino acids.
Chemically similar amino acids often have similar codons. Hydrophobic amino acids are often encoded by codons with U in the 2nd position, and all codons with U at the 2nd position encode hydrophobic amino acids. The major codon specifying initiation of translation is AUG. Using data from the genes identified by the complete genome sequence of E. AUG is used for genes. GUG is used for genes. UUG is used for genes. AUU is used for 1 gene. CUG may be used for 1 gene.
Regardless of which codon is used for initiation, the first amino acid incorporated during translation is f-Met in bacteria. Of these three codons, UAA is used most frequently in E. UAG is used much less frequently. UAA is used for genes. UGA is used for genes. UAG is used for genes.
The genetic code is almost universal. In the rare exceptions to this rule, the differences from the genetic code are fairly small. Differential codon usage. Various species have different patterns of codon usage. The pattern of codon usage may be a predictor of the level of expression of the gene. In general, more highly expressed genes tend to use codons that are frequently used in genes in the rest of the genome.
This has been quantitated as a "codon adaptation index". Thus in analyzing complete genomes, a previously unknown gene whose codon usage profile matches the preferred codon usage for the organism would score high on the codon adaptation index, and one would propose that it is a highly expressed gene. Likewise, one with a low score on the index may encode a low abundance protein. The observation of a gene with a pattern of codon usage that differs substantially from that of the rest of the genome indicates that this gene may have entered the genome by horizontal transfer from a different species.
The preferred codon usage is a useful consideration in "reverse genetics". If you know even a partial amino acid sequence for a protein and want to isolate the gene for it, the family of mRNA sequences that can encode this amino acid sequence can be determined easily. Because of the degeneracy in the code, this family of sequences can be very large.
Since one will likely use these sequences as hybridization probes or as PCR primers, the larger the family of possible sequences is, the more likely that one can get hybridization to a target sequence that differs from the desired one. Thus one wants to limit the number of possible sequences, and by referring to a table of codon preferences assuming they are known for the organism of interest , then one can use the preferred codons rather than all possible codons.
This limits the number of sequences that one needs to make as hybridization probes or primers. Wobble in the anticodon. In contrast, the first two positions of the codon form regular Watson-Crick base pairs with the last two positions of the anticodon.
This flexibility at the "wobble" position allows some tRNAs to pair with two or three codons, thereby reducing the number of tRNAs required for translation. Wobble rules. Types of mutations. Base substitutions. Just as a reminder, there are two types of base substitutions. The same class of nucleotide remains.
Examples are A substituting for G or C substituting for T. Over evolutionary time, the rate of accumulation of transitions exceeds the rate of accumulation of transversions. Effect of mutations on the mRNA. Depending on the particular replacement, it may or may not have a detectable phenotypic consequence. Some replacements, e. Other replacements, such as valine for a glutamate at a site that causes hemoglobin to polymerize in the deoxygenated state, cause significant pathology sickle cell anemia in this example.
They almost always have serious phenotypic consequences. Not all base subsitutions alter the encoded amino acids. However, there are several exceptions to this rule. This is one of the strongest supporting arguments in favor of model of neutral evolution, or evolutionary drift, as a principle cause of the substitutions seen in natural populations.
The template strand of a sample of double-helical DNA contains the sequence:. Will the resulting amino acid sequence be the same as in b? Some proteins are enzymes that catalyze biochemical reactions. Other proteins play roles in DNA replication and transcription. Yet other proteins provide structural support for the cell, create channels through the cell membrane, or carry out one of many other important cellular support functions. This page appears in the following eBook. Aa Aa Aa.
The ribosome assembles the polypeptide chain. What is the genetic code? More on translation. How did scientists discover how ribosomes work? What are ribosomes made of? Is prokaryotic translation different from eukaryotic translation? Figure 1: In mRNA, three-nucleotide units called codons dictate a particular amino acid. For example, AUG codes for the amino acid methionine beige. The codon AUG codes for the amino acid methionine beige sphere. The codon GUC codes for the amino acid valine dark blue sphere.
The codon AGU codes for the amino acid serine orange sphere. The codon CCA codes for the amino acid proline light blue sphere. The codon UAA is a stop signal that terminates the translation process. The idea of codons was first proposed by Francis Crick and his colleagues in During that same year, Marshall Nirenberg and Heinrich Matthaei began deciphering the genetic code, and they determined that the codon UUU specifically represented the amino acid phenylalanine.
Following this discovery, Nirenberg, Philip Leder, and Har Gobind Khorana eventually identified the rest of the genetic code and fully described which codons corresponded to which amino acids. Reading the genetic code. Redundancy in the genetic code means that most amino acids are specified by more than one mRNA codon. Methionine is specified by the codon AUG, which is also known as the start codon.
Consequently, methionine is the first amino acid to dock in the ribosome during the synthesis of proteins. Tryptophan is unique because it is the only amino acid specified by a single codon. The remaining 19 amino acids are specified by between two and six codons each. Figure 2 shows the 64 codon combinations and the amino acids or stop signals they specify.
Figure 2: The amino acids specified by each mRNA codon. Multiple codons can code for the same amino acid. Figure Detail. What role do ribosomes play in translation? As previously mentioned, ribosomes are the specialized cellular structures in which translation takes place. This means that ribosomes are the sites at which the genetic code is actually read by a cell. Figure 3: A tRNA molecule combines an anticodon sequence with an amino acid.
These nucleotides represent the anticodon sequence. The nucleotides are composed of a ribose sugar, which is represented by grey cylinders, attached to a nucleotide base, which is represented by a colored, vertical rectangle extending down from the ribose sugar.
The color of the rectangle represents the chemical identity of the base: here, the anticodon sequence is composed of a yellow, green, and orange nucleotide. At the top of the T-shaped molecule, an orange sphere, representing an amino acid, is attached to the amino acid attachment site at one end of the red tube.
During translation, ribosomes move along an mRNA strand, and with the help of proteins called initiation factors, elongation factors, and release factors, they assemble the sequence of amino acids indicated by the mRNA, thereby forming a protein.
In order for this assembly to occur, however, the ribosomes must be surrounded by small but critical molecules called transfer RNA tRNA.
Each tRNA molecule consists of two distinct ends, one of which binds to a specific amino acid, and the other which binds to a specific codon in the mRNA sequence because it carries a series of nucleotides called an anticodon Figure 3. In this way, tRNA functions as an adapter between the genetic message and the protein product. The exact role of tRNA is explained in more depth in the following sections. What are the steps in translation?
Like transcription, translation can also be broken into three distinct phases: initiation, elongation, and termination. All three phases of translation involve the ribosome, which directs the translation process. Multiple ribosomes can translate a single mRNA molecule at the same time, but all of these ribosomes must begin at the first codon and move along the mRNA strand one codon at a time until reaching the stop codon.
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