THE PRINCIPAL FEATURES OF THE GENETIC CODE-STELLA ANGELI THE PRINCIPAL FEATURES OF THE GENETIC CODE Student number: 086223452 Molecular Biochemistry tutorial group: I 0 THE PRINCIPAL FEATURES OF THE GENETIC CODE-STELLA ANGELI The principal features of the genetic code Have you ever wondered about the importance of the genetic code in the continuity of life? The fact is that a possible destruction of the code would be a total disaster for all living species, while is essential for the “building” of polypeptide chains, which have specific functions that are vital for all the organisms. The revealing of the genetic code is based on a complicate process: DNA replication, transcription and translation, called the central dogma of the molecular biology (Francis Crick 1957). The Central Dogma: DNA encodes the information to make RNA.........and RNA molecules function together to make protein Figure 1: the central dogma of the molecular biology All the genetic information is “hidden” in the DNA molecule. Therefore, it has to unwind and copy the two parent strands for the production of two identical complementary strands, which is vital for the perpetuation of the genetic information. When the two complementary strands are synthesized, transcription is the next step. Transcription is the process of RNA synthesis by using the DNA strand as a template and the product is the mature mRNA, which includes the genetic code that is ready to be translated. The final process is translation, the synthesis of a polypeptide chain using the mature mRNA. All the flowing of information from the genes to proteins depends on the triplet code. The sequence of three bases is a codon (Crick 1958), which specifies an amino acid. The whole process is based on the translation of the base language 1 THE PRINCIPAL FEATURES OF THE GENETIC CODE-STELLA ANGELI to the amino acids language. Small and large subunits of the ribosome and the tRNA work together in order to create a polypeptide chain. Figure 2: DNA replication Figure 3: transcription Figure 4: mature mRNA 2 Figure 5: translation THE PRINCIPAL FEATURES OF THE GENETIC CODE-STELLA ANGELI Figure 6: The genetic code The genetic code was discovered by Francis Crick in 1953 when DNA molecule was already proposed. The principal features of the code are: 1. The code is triplet, unpunctuated and nonoverlapping Francis Crick tried to find out how the genetic code works by making experiments. It is a fact that there are 20 amino acids and only 4 bases that specify them. He made the hypothesis that two bases specify one amino acid, therefore, while the bases are 4, the result is 4 2 =16 combinations. That meant the combinations were not enough for all the amino acids. The final estimation was the right one: three bases specify one amino acid (43 =64 possible combinations) and the triplets are called codons. While Francis Crick was doing experiments using bacteriophage crosses to indicate in vitro that the genetic code was actually a triplet code, another scientist, named Marshall Nirenberg, who used poly-U as a control RNA template in his experiment, discovered that UUU was the codon for phenylalanine and after that he could solve the whole code. 3 THE PRINCIPAL FEATURES OF THE GENETIC CODE-STELLA ANGELI Francis Crick comments on Nirenbergs discovery: "What he had discovered was that he could add an artificial message to a test-tube system that synthesized proteins and get it to direct some synthesis. In detail, he had added poly U -- the RNA message consisting almost entirely of a sequence of uracils -- to the system and it had synthesized phenylalanine. This suggested that UUU (assuming a triplet code) was a codon for phenylalanine (one of the "magic twenty" amino acids), as indeed it is... Nevertheless it was an epoch-making discovery, after which there was no looking back." (Francis Crick in "What Mad Pursuit" on a visit to the Biochemical Congress in Moscow in 1961). Crick’s comment indicated the importance of that discovery because after that everything was clear for the solving of the genetic code. Figure 7: Francis Crick Figure 8: The experiment which used uracil (U) as a template produced a protein entirely made up of the amino acid phenylalanine (F). The first letter of the genetic code was hence identified.( Lotta Fredholm, Science Journalist) 4 THE PRINCIPAL FEATURES OF THE GENETIC CODE-STELLA ANGELI Apart from a triplet code, the genetic code is unpunctuated, that means that there are no gabs between the triplets, and nonoverlapping, mmmiwhich means that triplets are read in order as a result to have diversity hhhhhand each nucleotide belongs to only one codon. If it was overlapping, gggggithere would be less combinations of the amino acids. Figure 9: several possibilities how triplets might code for amino acids 5 THE PRINCIPAL FEATURES OF THE GENETIC CODE-STELLA ANGELI 2. The Genetic Code is Unambiguous The code is unambiguous and that means that each codon specifies a specific amino acid and only that. For example, GCU codes for the amino acid alanine and no other amino acid. (Nature,192 1227; 1961)| 3. The code is degenerate Degeneration is one of the most important features of the genetic code because it has a protective role in all the organisms. Most of the amino acids can be specified by more than one codon (e.g. glutamic acid is specified by GAA and GAG codons), which differ in the third (wobble) position. The codons that specify the same amino acid are called synonyms. Only two amino acids are specified by only one codon: methionine (AUG) and tryptophan (UGG). Degeneracy is a huge property because it gives protection against mutation. For example, if a codon is influenced by mutation in the third position, there would not be a change in the synthesized polypeptide chain because there are other codons that specify that specific amino acid. David Tyler said in his article, "Optimal features of the genetic code": "…the assignment of amino acids to codons appears to be optimal for minimizing the effect of translational misread errors". This is because that kind of errors do not influence the translated protein. 4. There is one start and three stop codons The start codon in all the organisms is AUG and specifies methionine. The stop codons are UAG, UGA and UAA. The presence of these codons on the mRNA molecule leads to the termination of the polypeptide chain synthesis. 5. The Genetic Code is nearly Universal The genetic code is nearly universal because it is the same worldwide .All the organisms have the same genetic code, thus, the 6 THE PRINCIPAL FEATURES OF THE GENETIC CODE-STELLA ANGELI mRNA from any organism can be translated into plant, animal or bacteria cell extract in vitro and produce the exact same protein. On the other hand there are some exceptions in the genetic code of mitochondria and protozoan species, as figure 10 and 11 show (Nature, vol.367, 1994) Figure 10 : the genetic code in nucleus 7 Figure 11: the genetic code in mitochondria THE PRINCIPAL FEATURES OF THE GENETIC CODE-STELLA ANGELI Finally, by having an overview, the genetic code includes all the information, which is going to be translated for the protein synthesis. Therefore the importance of its features is vital for the survival of all organisms, but there are still so many unknown secrets of the code that are ready to be revealed. Once, Tobias Bollenbach, wrote in his article: "Looking deeper into the structure of the code, we wonder what other remarkable properties it may bear. While our understanding of the genetic code has increased substantially over the last decades, it seems that exciting discoveries are waiting to be made." (Tobias Bollenbach, Kalin Vetsigian, and Roy Kishony, 2007, Genome Research). __________________________________________________________ ________________________________________________________________ REFERENCES 1. Ambrogelly A. and Palioura S., (2007), Natural Chemical Biology 3, 29-35 2. Ansary Z. A., (2007), Chemical crosshairs on the central dogma, Natural Chemical Biology, vol,3, numb1, pp.1-7 3. Bollenbanch T., Vetsigian K., Kishony R.,(2007) Genome research, 17:401-404 4. Campbell and Reece, The molecular basis of inheritance, pp.305-316 5. Campbell and Reece, From gene to protein, pp.328-331 6. Hayes B., (2004), Genome biology: on the genetic code, science week,93:494 7. Itzkovitz S. and Alon U,(2007), The genetic code is nearly optimal for allowing additional information within protein-coding sequences, Genome research 8. Maddox J. (2004), The genetic code by numbers, Nature, vol.367, pp.111 9. Mathews, Holde. Van,(2000) aherrn , third edition, pp.104-107 Ahern’s Biochemisrtey 10. Novozhilov S. A., wolf I.Y., Koonin V,E, Education of the genetic code: partial optimization of a random code for robustuess to translation error in a ragged fitness landscape, Biology direct (2007). 11. Stryer L. Chapter 5, Flow of the genetic information, Biochemistry, pp. 103-111 12. Stryer L. Chapter 34, Protein synthesis, Biochemistry, pp. 886-7 13. http://www.mun.ca/biochem/courses/3107/Topics/Genetic_code.html 14. 15. 16. 17. http://en.wikipedia.org/wiki/Genetic_code http://www.brighthub.com/education.aspx http://nobelprize.org/educational_games/medicine/gene-code/history.html http://www.arn.org/blogs/index.php/literature/2007/03/01/optimality_features_in_the_ge netic_code 18. http://www.bio.iupui.edu/biocourses/N100/imag... 19. http://www.accessexcellence.org/RC/VL/GG/genetic.php 8 THE PRINCIPAL FEATURES OF THE GENETIC CODE-STELLA ANGELI 20. http://www.emunix.emich.edu/~rwinning/genetics/code.htm IMAGES Figure 1 taken from: http://www.accessexcellence.org/RC/VL/GG/genetic.php Figure 2 taken from: http://cellbiology.med.unsw.edu.au/units/images/DNA_replication_fork.png Figure 3 taken from: http://porpax.bio.miami.edu/~cmallery/150/gene/c7.17.7b.transcription.jpg Figure 4 taken from: http://genome.wellcome.ac.uk/assets/GEN10000674.jpg Figure 5 taken from: http://nobelprize.org/educational_games/medicine/dna/a/translation/pics/translation2. gif Figure 6 taken from: http://www.emc.maricopa.edu/faculty/farabee/BIOBK/code.gif Figure 7 taken from: http://www.skeptic.com/eskeptic/04-07-30images/crick.jpg Figure 8 taken from: http://nobelprize.org/educational_games/medicine/genecode/history.html Figure 9 taken from: http://bass.bio.uci.edu/~hudel/bs99a/lecture20/lecture1_3.html Figure 10,11 taken from: http://www.mun.ca/biochem/courses/3107/images/Nuclear_variants.GIF 9 THE PRINCIPAL FEATURES OF THE GENETIC CODE-STELLA ANGELI 10