the genetic code
Components
The history of the genetic code ……………………………………………………………..….…
Cracking the genetic code…………………………………………………………………………..
The genetic code…………………………………………………………………………………….
Exceptions of the standard genetic code ……………………………………………..………....
Theories on the origin of the genetic code………………………………………….…………
Genetic code mutations……………………………………………………………….………….
New researches in the genetic code……………………………………………….………….
The history of the genetic code:
Before cracking the genetic code:1724: the egg cells was discovered and the thought that the female is the copper of the genetic code but later in the same year they discovered the virgin birth any they had to face this fact and tried to get an explanation .
1799: George shaw he was a British natural geologist was the first one to say that “there is a genetic material which passes from generation to another “
1831: a scotch botanist Robert brown discovered that cell contain a nucleus which lead to discover the DNA and the genetic code.
1856: Ricardo.M.lantican publish is his book (genes & the genetic code) “hereditably traits were determined by particulate units that handed from parents to their children in an organized pattern.
1859: Darwin’s book(the origin of species) and his theory about evolution changed the scientific society , but in 1960s they discovered the universal genetic code which was the best evidence on Darwin’s theory .
1869: the first one to isolate the DNA was a Swiss physician Friedrich Miescher who discovered a microscopic substance in the pus of discarded surgical bandages. As it resided in the nuclei of cells, he called it "nuclein"
1921: lord Gifford mogg a professor on Oxford University become the first one to isolate genes from semen this research pave the way for a technique called knouch out.
1928: Griffith made an experiment on penococcus bacteria proved that the DNA is the genetic material.
1952: Watson and crick changed the way of genetics when the successfully demonstrate the structure of the DNA. And then in 1955 they were able to identify the chromosome chemical components and prove that it’s a molecule made of DNA which demonstrate the genetic code in each organism.
1957: crick actually succeed to step the first steps in the genetic code showing that the genetic information is translated into proteins that works in the cell . he worked out just how four letters (A-C-G-T) were translated into a word of code of amino acids (the building blocks of protein).
After cracking the genetic code:1961: the first time the code was cracked by Marshall Nirenberg and Heinrich Matthaei .
1964: cracking the universal genetic code .
1966: in April 17 1966 they made a data storage that contain all codes of the genetic code.
1967: they see that (mamels-amphubians- bacteria) have the same universal genetic code but the different is in numbers of codes in the organism which determinate the higher or lower organisms.
1977: to brake the genome into pieces a technique was first developed by: fred sanger they read a simple virus 5375 letters in the genetic code. In this technique many copies of genome are broken up randomly into pieces that over lapped and compared.
1900: they found the genetic code in 17 million year old leaf.
1992: the genetic alphabets (A-C-G-T) have been expanded artificially.
1996: cracking the genetic code in yeasts.
1998: international team of investigation in the U.S.A & Britain reported the genome of caenarhabditis elegans using the knowledge of the concept 19000genes and they found that 15% genes as having the know function and play a role in genes excretion.
1999: the first map of human chromosome made by: tom buerkle.
2000-2006: the human genome project.
How the code was cracked:
The first step was to identify DNA as the carrier of genetic information. This happened when Oswald Avery, a bacteriologist working at the Rockefeller Institute in New York, discovered that the substance responsible for producing inheritable change in the Pneumococcus organisms (disease-causing bacteria) he had studied for so long was neither a protein nor a lipid, but in fact deoxyribonucleic acid (DNA). He and his colleagues Colin Macleod and Macklin McCarty published a paper in 1944 in which they suggested that DNA was responsible for transferring genetic information. The idea was not easily accepted.
After reading Avery, MacLeod, and McCarty’s paper, many scientists changed the focus of their research to further investigate nucleic acids. One of the most successful, Erwin Chargaff, found a clue when he discovered that the makeup of DNA differs from one species to another. He also studied the ratios of bases in the DNA of different species and concluded that the two bases adenine (A) and thymine (T) appeared in relatively equal amounts, as did guanine (G) and cytosine (C). This helped pave the way for discoveries to come about the shape of DNA.
In the early 1950s, then, scientists knew that DNA was genetic material and that it was formed of sugars, phosphate groups, and equally matched bases. James Watson and Francis Crick, working together at Cambridge University in England, assimilated all this information along with the help of Maurice Wilkins and expert X-ray crystallography images prepared by Rosalind Franklin, both of King’s College in London. In 1953 Watson and Crick came up with their historic model of the shape of DNA: the double helix.
As Watson and Crick discovered, DNA is in the shape of a double helix with the outside strands made of phosphate and sugar combinations. The base pairs link to form the inner ladder-like rungs that hold the outside strands together. Identifying the shape of DNA was a major breakthrough in genetic research, for which Watson, Crick, and Wilkins won the Nobel Prize in Physiology or Medicine in 1962.
But how did the information on DNA get translated into proteins? What was nature's genetic code?
The first scientist after Watson and Crick to find a measure of success with the coding problem was Russian physicist George Gamow. He envisioned the relationship between DNA structure and protein synthesis as a numerical cryptanalytic problem. Gamow surmised that the goal for scientists was to learn how a long sequence of 4 nucleotides determines the assignment of long protein sequences composed of 20 amino acids. Gamow published a short piece in the October 1953 issue of Nature that proposed a solution called the “diamond code”, an overlapping triplet code based on a combinatorial scheme in which 4 nucleotides arranged 3-at-a-time would specify 20 amino acids. They knew there was a total of four bases (guanine, cytosine, adenine, and thymine). So if there were two bases in each codon, then there would only be the possibility of (4 x 4) sixteen unique combinations of bases, or sixteen amino acids. But there were 20 known amino acids. So most assumed there would be at least three bases in each codon, providing (4 x 4 x 4) 64 possible combinations
the diamond code
Somewhat like a language, this highly restrictive code was primarily hypothetical, based on then-current knowledge of the behavior of nucleic acids and proteins.
Gamow’s coding scheme generated a great deal of enthusiasm among other scientists. To foster communication and camaraderie, Gamow founded the RNA Tie Club, a group of 20 hand-picked scientists (corresponding to the 20 amino acids) who would circulate notes and manuscripts on the coding problem and (not inconsequentially) consume wine, beer, and whiskey at periodic meetings. Each member of the club was given the moniker of an amino acid, and all were presented with a diagrammed tie and tiepin made to Gamow’s specification. Although geographically dispersed, the Tie Club brought physical scientists and biologists together to work on one of the most challenging and important problems in modern science.
By mid-1954, Gamow had accepted that his diamond code was not accurate, yet he and others continued to deliberate over the various codes presented by disparate researchers. In truth, the notion of a “code” as the key to information transfer was not articulated publicly until late 1954, when Gamow, Martynas Ycas, and Alexander Rich published an article that defined the code idiom for the first time since Watson and Crick casually mentioned it in a 1953 article. Yet the concept of coding applied to genetic specificity was somewhat misleading, as translation between the 4 nucleic acid bases and the 20 amino acids would obey the rules of a cipher instead of a code. As Crick acknowledged years later, in linguistic analysis, ciphers generally operate on units of regular length (as in the triplet DNA scheme), whereas codes operate on units of variable length (e.g., words, phrases). But the code metaphor worked well, even though it was literally inaccurate, and in Crick’s words, “‘Genetic code’ sounds a lot more intriguing than ‘genetic cipher’.” Codes and the information transfer metaphor were extraordinarily powerful, and heredity was often described as a biological form of electronic communication.
By 1955, research suggested that a non overlapping code was more plausible than Gamow’s original notion of overlapping triplets. By 1961, Crick and his colleagues (including Sydney Brenner) concluded that the nucleotides of each triplet did not belong to any other triplet. They also postulated that sets of triplets are arranged in continuous linear sequence starting at a fixed point in a polynucleotide chain without breaks, an aspect of the code that was termed “commaless”. The notion of a “degenerate code” was also introduced, which meant that more than one triplet can code for a particular amino acid (a possibility inherent in the fact that there were 64 possible triplets out of 4 base pairs and only 20 amino acids to be coded for). These discoveries in the decade before 1961 brought scientists closer to a clear vision of what the genetic code might look like, but it was experimental biochemical investigation in the 1960s that finally led biologists to the solution of the code.
However, despite all the scientists working on the problem, in 1961 the basic mystery remained: which series of bases specified which amino acids? What, in fact, was the genetic code?
The first steps to solving the Genetic Code depended on the development of a cell-free in vitro translation system by Paul Zamecnik . This system which consisted of a membrane-free cell supernatent, ATP, GTP, radioactively labelled amino-acids and RNA, was capable of directing the synthesis of radioactively labeled protein.
Marshall Nirenberg came to the NIH in 1957. By the end of the following year he had found his research calling. He decided to concentrate on nucleic acids and protein synthesis, thinking this might lead to something more. He wrote in his research notebook, “would not have to get polynucleotide synthesis very far to break the coding problem. Could crack life's code!” Nirenberg spent the next few years on the first part of his task: creating experiments to show that RNA could trigger protein synthesis.
Their experiment required a cell-free system, created when cell walls are ruptured and release their contents. The material inside cells is called cytoplasm, or sap, which can still synthesize protein but only when the correct kind of RNA is added, allowing the scientists to control the experiment. Nirenberg and Matthaei chose E. Coli bacteria cells, and ground them up using a mortar and pestle to release the cytoplasm, or sap, they would use in their experiments. The scientists, working by themselves for the most part, and often late into the night, would use the sap itself to force the creation of a protein. The experiment used 20 test tubes, each filled with a different amino acid. For each individual experiment, 19 test tubes were “cold” and one was radioactively tagged so the scientists could watch the reaction. The “hot” amino acid would change every time they did the experiment. Nirenberg wanted to know which amino acid would be incorporated into a protein following the addition of a particular type of synthetic RNA.
On Saturday, May 27, 1961, at three o'clock in the morning, Matthaei combined the synthetic RNA made only of uracil (called poly-U) with cell sap derived from E. coli bacteria and added it to each of 20 test tubes. This time the “hot” test tube was phenylalanine. The results were spectacular and simple at the same time: after an hour, the control tubes showed a background level of 70 counts, whereas the hot tube showed 38,000 counts per milligram of protein. The experiment showed that a chain of the repeating bases uracil forced a protein chain made of one repeating amino acid, phenylalanine. The code could be broken! UUU=Phenylalanine was a breakthrough experiment result for Nirenberg and Matthaei.
Marshall Nirenberg and Heinrich Matthaei were using such a system to investigate the synthesis of viral proteins. They used theTobacco Mosaic Virus (TMV) RNA as their experimental template. As a control RNA template they used the homopolymer poly(U) which they synthesized from UDP using polynucleotide phosphorylase. They did not expect that this template would code for or direct protein synthesis.
They two kept their breakthrough a secret from the larger scientific community–though many NIH colleagues knew of it –until they could complete further experiments with other strands of synthetic RNA (Poly-A, for example) and prepare papers for publication. They had solved with an experiment what others had been unable to solve with theoretical explanations and mathematical models.
This period, between 1961 and 1962, is often referred to as the “coding race” because of the competition between Ochoa's and Nirenberg's labs. Indeed, the two laboratories completed the base composition part of the code almost simultaneously. However, Ochoa’s laboratory stopped working on the problem when they realized how close Nirenberg and his colleagues were to completing the sequencing.
By 1965, Nirenberg, with help from his NIH colleagues, had become the first to complete the sequencing of the code. The language of DNA was understood. Once completely solved, the genetic code could be expressed in a chart. By looking up the sequence of nucleotide bases, readers could identify the resulting amino acid. To read the code, select a letter from the left, right, and top columns, such as U-C-A. This combination represents an mRNA codon. Draw imaginary horizontal and vertical lines to connect the letters. They intersect at the amino acid for which they code. For example, UCA is the code for serine.
The importance of the research that was awarded the Nobel Prize in Physiology or Medicine in 1968 cannot be overestimated. Cracking the code of life paved the way for a tremendous boom in molecular biology, enabling scientists to put together strings of DNA and RNA to produce selected proteins.
One example where this technique is used is in the production of pharmaceuticals. The DNA that encodes the protein you want is synthesized and put in bacteria. A new copy of the desired protein is produced every time the bacterium divides. Since an E. coli bacteria can produce approximately 17 million daughter cells during an 8-hour working day (and bacteria work 24 hours a day, 7 days a week), the production is very efficient. In this fashion it is now possible to make many useful proteins, for example insuline (to treat diabetic patients) and different coagulation factors that are needed by patients suffering from hemophilia.
The use of poly(A) and poly(C) as templates similarly showed that AAA was a codon for lysine and that CCC was a codon for proline. However, poly(G) did not work at all in the system.This use of homopolymers is clearly quite limited. The use of random mixed copolymers helped to extend the utility of the system and the information obtained from it.
Random copolymers can be synthesized from a mixture of two ribonucleotides with polynucleotide phosphorylase. Thus if ADP and CDP are used in a 5:1 ratio, then the frequency of each possible triplet in the synthesized RNA will vary according to this ratio. For example, AAA triplets will be found 100 times more frequently than CCC triplets.
| CODON | FREQUENCY | RELATIVE FREQUENCY |
| AAA | 0.579 | 100 |
| AAU | 0.116 | 20 |
| AUA | 0.116 | 20 |
| UAA | 0.116 | 20 |
| AUU | 0.023 | 4 |
| UAU | 0.023 | 4 |
| UUA | 0.023 | 4 |
| UUU | 0.00463 | 1 |
By measuring the ratios of the different amino acids that are incorporated into protein using random colpolymer templates, it is possible to narrow down the range of codons that correspond to particular amino acids.
This method did not yield all of the codon assignments. That required the chemical synthesis of short oligonucleotides with defined sequences
Once the code was solved, and while the sequencing was being finished, Nirenberg turned to the examination of some questions about what it meant to have discovered what people referred to as “the code of life.” One question that particularly fascinated him was the issue of universality. He and his colleagues had done all their experiments with bacteria. Would the results change if different species were used?
Experiments with toads and guinea pigs showed that the code was almost universal. Nirenberg later recalled looking out the window of his office and marveling that he, the tree, and the squirrel should have turned out to be so biologically similar. They mandged to crack the genetic code of alots of organism like nematode and other bacteria and they found a fact which the genetic code is universal.
What is the genetic code??
It is the set of rules by which information encoded in genetic material. Genetic information is stored as nucleotide sequences in DNA (or RNA) molecules. This sequence specifies the identity and position of the amino acids in a particular protein. Amino acids are the building blocks of proteins in the same way that nucleotides are the building blocks of DNA. However, though there are only four possible bases in DNA (or RNA), there are 20 possible amino acids in proteins.
List of the 20 amino acids:
| Amino Acid | 3-Letter | 1-Letter | Side chain polarity |
| Ala | A | nonpolar | |
| Arg | R | polar | |
| Asn | N | polar | |
| Asp | D | polar | |
| Cys | C | nonpolar | |
| Glu | E | polar | |
| Gln | Q | polar | |
| Gly | G | nonpolar | |
| His | H | polar | |
| Ile | I | nonpolar | |
| Leu | L | nonpolar | |
| Lys | K | polar | |
| Met | M | nonpolar | |
| Phe | F | nonpolar | |
| Pro | P | nonpolar | |
| Ser | S | polar | |
| Thr | T | polar | |
| Trp | W | nonpolar | |
| Tyr | Y | polar | |
| Val | V | nonpolar |
The genetic code is a sort of "bilingual dictionary" which translates the language of DNA into the language of proteins. In the genetic code the letters are the four bases A, C, G, and T (or U instead of T in RNA). Obviously, the four bases of DNA are not enough to code for 20 amino acids. A sequence of two bases is also insufficient, because this permits coding for only 16 of the 20 amino acids in proteins. Therefore, a sequence of three bases is required to ensure enough combinations or "words" to code for all 20 amino acids. Since all words in this DNA language, called codons, consist of three letters, the genetic code is often referred to as the triplet code.
| U | C | A | G |
| UUU Phe UUC Phe UUA Leu UUG Leu | UCU Ser UCC Ser UCA Ser UCG Ser | UAU Tyr UAC Tyr UAA Stop UAG Stop | UGU Cys UGC Cys UGA Stop UGG Trp |
| CUU Leu CUC Leu CUA Leu CUG Leu | CCU Pro CCC Pro CCA Pro CCG Pro | CAU His CAC His CAA Gln CAG Gln | CGU Arg CGC Arg CGA Arg CGG Arg |
| AUU Ile AUC Ile AUA Ile AUG Met | ACU The ACC Thr ACA Thr ACG Thr | AAU Asn AAC Asn AAA Lys AAG Lys | AGU Ser AGC Ser AGA Arg AGG Arg |
| GUU Val GUC Val GUA Val GUG Val | GCU Ala GCC Ala GCA Ala GCG Ala | GAU Asp GAC Asp GAA Glu GAG Glu | GGU Gly GGC Gly GGA Gly GGG Gly |
Each codon specifies a particular amino acid. Because there are 64 possible codons (for example 43 = 64 different 3-letter "words" can be generated from a 4-letter "alphabet") and only 20 amino acids, several different codons specify the same amino acid, so the genetic code is said to be degenerate. However, the code is unambiguous because each codon specifies only one amino acid. The sequence of codons is not interrupted by “commas” and is always read in the same frame of reference, starting with the same base every time. So the "words" never overlap.
Since DNA never leaves the nucleus, the information it stores is not transferred to the cell directly. Instead, a DNA sequence must first be copied into a messenger RNA molecule, which carries the genetic information from the nucleus to protein assembly sites in the cytoplasm. There it serves as the template for protein construction. The sequences of nucleotide triplets in messenger RNA are also referred to as codons.
There are seven main characteristics of the genetic code:
1. It is made up of codons, which are triplets of bases. Each codon specifies a specific amino acid.
2. The codons do not overlap; that is, the sequence GCCCAC contains two triplets, “GCC” and “CAC” not counting the “CCC” and other subsequent three-letter sequences
3. The code includes punctuation in the form of three “stop” codons that do not code for an amino acid: UAA, UAG, and UGA.
4. The genetic code is known as a “degenerate” code. This means that each amino acid is triggered by between one and six codons. (There are only 20 amino acids and 64 possible codon triplets).
5. To read each gene and glean the necessary information to form proteins, cells begin at a fixed and particular starting point on the mRNA strand. The initiation codon is AUG (methionine) which called starting codone.
6. The mRNA strand is read from the 5' to the 3' end.
7. If there are mutations or errors in the DNA, the message may be changed and incorrect protein formation results.
And the most important rule of the genetic code that IT’S UNIVERSAL The only exceptions occur in mitochondria and chloroplasts and in some protozoa and I will talk about this exceptions.
Reading the frame sequence:
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. 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 in which a protein sequence is translated 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. One reason for the rareness of frame-shifted mutations being inherited is that if the protein being translated is essential for growth under the selective pressures the organism faces, absence of a functional protein may cause lethality before the organism is viable.
Start and stop codones:
Translation starts with a chain start codon . Unlike stop codons, the codon alone is not sufficient to begin the process. Nearby sequences and initiation factors are also required to start translation. The most common start codon is AUG, which codes for methionine, so most amino acid chains start with methionine.
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. The other two stop codons were named 'ochre" and "opal" in order to keep the "color names" theme. Stop codons are also called termination codons and they signal release of the nascent polypeptide from the ribosome due to binding of release factors in the absence of cognate tRNAs with anticodons complementary to these stop signals.
Degeneracy of the genetic code:
The genetic code has redundancy but no ambiguity (see the codon tables above 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 glutamic acid is specified by GAA and GAG codons (difference in the third position), the amino acid leucine is specified by UUA, UUG, CUU, CUC, CUA, CUG codons (difference in the first or third position), while the amino acid serine is specified by UCA, UCG, UCC, UCU, AGU, AGC (difference in the first, second or third position).
A position of a codon:
fourfold degenerate site if any nucleotide at this position specifies the same amino acid. For example, the third position of the glycine codons (GGA, GGG, GGC, GGU) is a fourfold degenerate site, because all nucleotide substitutions at this site are synonymous. they do not change the amino acid. Only the third positions of some codons may be fourfold degenerate. twofold degenerate site if only two of four possible nucleotides at this position specify the same amino acid. For example, the third position of the glutamic acid codons (GAA, GAG) is a twofold degenerate site. In twofold degenerate sites, the equivalent nucleotides are always either two purines (A/G) or two pyrimidines (C/U), so only transversional substitutions (purine to pyrimidine or pyrimidine to purine) in twofold degenerate sites are nonsynonymous. non-degenerate site if any mutation at this position results in amino acid substitution. threefold degenerate site There is only one where changing three of the four nucleotides has no effect on the amino acid, while changing the fourth possible nucleotide results in an amino acid substitution. This is the third position of an isoleucine codon: AUU, AUC, or AUA all encode isoleucine, but AUG encodes methionine. In computation this position is often treated as a twofold degenerate site.There are three amino acids encoded by six different codons: serine, leucine, arginine. Only two amino acids are specified by a single codon; one of these is the amino-acid methionine, specified by the codon AUG, which also specifies the start of translation; the other is tryptophan, specified by the codon UGG. The degeneracy of the genetic code is what accounts for the existence of silent mutations.
| numbers of codons | amino acids |
| 1 | Met, Trp |
| 2 | Asn, Asp, Cys, Gln, Glu, His, Lys, Phe, Tyr |
| 3 | Ile |
| 4 | Ala, Gly, Pro, Thr, Val |
| 6 | Arg, Leu, Ser |
Degeneracy results because a triplet code designates 20 amino acids and a stop codon. Because there are four bases, triplet codons are required to produce at least 21 different codes. For example, if there were two bases per codon, then only 16 amino acids could be coded for (4²=16). Because at least 21 codes are required, then 4³ gives 64 possible codons, meaning that some degeneracy must exist.
Exception of the standerd genetic code:
Exceptions in the start and termination codons:While slight variations on the standard code had been predicted earlier. None were discovered until 1979, when researchers studying human mitochondrial genes discovered they used an alternative code. Many slight variants have been discovered since, including various alternative mitochondrial codes, as well as small variants such as Mycoplasma translating the codon UGA as tryptophan. In bacteria and archaea, GUG and UUG are common start codons. However, in rare cases, certain specific proteins may use alternative initiation (start) codons not normally used by that species. Exception in the fact that every codon translates into one amino acid: The exceptions so far are AUG, UGA and UAG .As AUG specifies both Methionine and N-formyl-Methionine, which is used to initiate protein synthesis in bacteria. In the second case, UGA specifies the twenty-first amino-acid selenocysteine as well as being a stop codon. And, in the last case, UAG specifies the twenty second amino acid pyrrolysine.
- selenocysteine. This amino acid is encoded by UGA. UGA is still used as a chain terminator, but the translation machinery is able to discriminate when a UGA codon should be used for selenocysteine rather than STOP. This codon usage has been found in certain Archaea, eubacteria, and animals (humans synthesize 25 different proteins containing selenium).
- pyrrolysine. In one gene found in a member of the Archaea, this amino acid is encoded by UAG. How the translation machinery knows when it encounters UAG whether to insert a tRNA with pyrrolysine or to stop translation is not yet known.
Exception at the fact the genetic code is universal: there are soures of the genetic material in the cell the first is the nucleus and the second source is the mitochondria and there are different between the genetic code in both but the most common exception is the use of UGA as a codon for Tryptophan in mitochondria.Theories on the origin of the genetic code
Despite the variations that exist, the genetic codes used by all known forms of life on Earth are very similar. Since there are many possible genetic codes that are thought to have similar utility to the one used by Earth life, the theory of evolution suggests that the genetic code was established very early in the history of life, with phylogenetic analysis of transfer RNA suggests that tRNA molecules evolved before the present set of aminoacyl-tRNA synthetases.
The genetic code is not a random assignment of codons to amino acids. For example, amino acids that share the same biosynthetic pathway tend to have the same first base in their codons, and amino acids with similar physical properties tend to have similar codons. There are three themes running through the many theories that seek to explain the evolution of the genetic code (and hence the origin of these patterns).
Recent experiments show that some amino acids have a selective chemical affinity for the base triplets that code for them. This suggests that the current complex translation mechanism involving tRNA and associated enzymes may be a later development, and that originally, protein sequences were directly template on base sequences. That the standard modern genetic code grew from a simpler earlier code through a process of "biosynthetic expansion". Here the idea is that primordial life 'discovered' new amino acids (e.g. as by-products of metabolism) and later back-incorporated some of these into the machinery of genetic coding. Although much circumstantial evidence has been found to suggest that fewer different amino acids were used in the past than today, precise and detailed hypotheses about exactly which amino acids entered the code in exactly what order has proved far more controversial That natural selection has led to codon assignments of the genetic code that minimize the effects of mutations. Genetic code mutations
THE MUTATION IS : a sudden change in the genetical material DNA .We also can call it a sudden change in the DNA sequence of gene.
We can dived the mutation according to its effect on the genetic material into:
I. macro mutations
II. micro mutations
macro mutations
There are 2 types of mutation in the macro mutations:
I. Numerical mutations: a change in the nuber of chromosomes.
II. Structural mutations: a change in the genetic codeDNA sequence.
I will talk about the structure mutations because it Accor in the genetic code.
Structure mutations
Deletion:
Mutations that result in missing DNA are called deletions. These can be small, such as the removal of just one "word," or longer deletions that affect a large number of genes on the chromosome.
Mutations that result in missing DNA are called deletions. These can be small, such as the removal of just one "word," or longer deletions that affect a large number of genes on the chromosome.
| Original | The fat rat saw the big cat |
| Deletion | The fat saw the big cat |
Insertion :
Mutations that result in the addition of extra DNA are called insertions. it general result in a nonfunctional protein.
Mutations that result in the addition of extra DNA are called insertions. it general result in a nonfunctional protein.
| Original | The fat rat saw the big cat |
| Insertion | The fat rat xlw saw the big cat |
Inversion:
In an inversion mutation, an entire section of DNA is reversed. A small inversion may involve only a few bases within a gene, while longer inversions involve large regions of a chromosome containing several genes.
In an inversion mutation, an entire section of DNA is reversed. A small inversion may involve only a few bases within a gene, while longer inversions involve large regions of a chromosome containing several genes.
| Original | The fat rat saw the big cat |
| Insertion | The fat tac gib eht was tar |
Translocation:
This is where information from one of two homologous chromosomes breaks and binds to the other. Usually this sort of mutation is lethal.
Micro mutations
Frame shift mutation:Protein-coding DNA is divided into codons three bases long, insertions and deletions can alter a gene so that its message is no longer correctly parsed. These changes are called frameshifts.
| Original | The fat rat saw the big cat |
| Frame Shift | The fat raa tsa wth ebi gca t |
Single base substation: Point mutation:
A point mutation is a simple change in one base of the gene sequence. This is equivalent to changing one letter in a sentence
A point mutation is a simple change in one base of the gene sequence. This is equivalent to changing one letter in a sentence
| Original | The fat rat saw the big cat |
| Point Mutation | The fat hat saw the big cat |
Nonsense mutations
With a nonsense mutation, the new nucleotide changes a codon that specified an amino acid to one of the STOP codons (TAA, TAG, or TGA). Therefore, translation of the messenger RNA transcribedfrom this mutant gene will stop prematurely. The earlier in the gene that this occurs, the more truncated the protein product and the more likely that it will be unable to function.
Silent mutations
Most amino acids are encoded by several different codons. For example, if the third base in the AAC codon for phen is changed to any one of the other three bases, Phen will still be encoded. Such mutations are said to be silent because they cause no change in their product and cannot be detected without sequencing the gene (or its mRNA).
Splice-site mutations
The removal of intron sequences, as pre-mRNA is being processed to form mRNA, must be done with great precision. Nucleotide signals at the splice sites guide the enzymatic machinery. If a mutation alters one of these signals, then the intron is not removed and remains as part of the final RNA molecule. The translation of its sequence alters the sequence of the protein product.The properties of the genetic code make it more fault-tolerant for point mutations. For example, in theory, fourfold degenerate codons can tolerate any point mutation at the third position, although codon usage bias restricts this in practice in many organisms; twofold degenerate codons can tolerate one out of the three possible point mutations at the third position. Sincetransition mutations (purine to purine or pyrimidine to pyrimidine mutations) are more likely than transversion (purine to pyrimidine or vice-versa) mutations, the equivalence of purines or that of pyrimidines at twofold degenerate sites adds a further fault-tolerance. A practical consequence of redundancy is that some errors in the genetic code only cause a silent mutation or an error that would not affect the protein 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; UNN encodes residues that are not hydrophilic
Even so, single point mutations can still cause dysfunctional proteins. For example, a mutated hemoglobin gene causes sickle-cell disease. In the mutant hemoglobin a hydrophilic glutamate (Glu) is substituted by the hydrophobic valine (Val), which reduces the solubility of β-globin. In this case, this mutation causes hemoglobin to form linear polymers linked by the hydrophobic interaction between the valine groups causing sickle-cell deformation of erythrocytes. Sickle-cell disease is generally not caused by a de novo mutation. Rather it is selected for in malarial regions (in a way similar to thalassemia), as heterozygous people have some resistance to the malarial Plasmodium parasite (heterozygote advantage). These variable codes for amino acids are allowed because of modified bases in the first base of the anticodon of the tRNA, and the base-pair formed is called a wobble base pair. The modified bases include inosine and the Non-Watson-Crick U-G basepair.
The new research in the genetic code
Scientists have deciphered the genetic blueprint of the duck-billed platypus, one of the oddest creatures on Earth: About two-thirds the size of the human genome Contains about 18,500 genes Has 52 chromosomes, including 10 sex chromosomes. more than 100 researchers from the US, UK and Australia, who took part in the study The genetic code of the fungus that causes dandruff has been cracked by an international team of scientists. an international group of researchers has sequenced of the Aedes genome, Aedes aegypti is the mosquito that is the scourge behind outbreaks of the deadly yellow, dengue and even chikungunya fevers that kill thousands of people in Africa, South America and Asia every year. At least 2.5 billion people—more than one third of the human population—are at risk of infection from dengue fever alone. WASHINGTON - Scientists have unraveled the DNA of another of our primate relatives, this time a monkey named the rhesus macaque
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