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Irene Kim November 20, 2012 DNA Model‐Building Deoxyribonucleic Acid, often known as the DNA, is the molecule of inheritance for all organisms on Earth. It is a three dimensional double helix of repeating nucleotides. The sides of a double helix are formed by the alternating sugar and phosphate that are joined together by covalent bonds. There are 10 nucleotides per every turn, about 3.4nm per helical turns. The “back bone” of the DNA is made of a ring shaped sugar called deoxyribose, and phosphoric acid (one phosphorus with four oxygen). The two single strands of DNA connect to each other with hydrogen bonding at their nitrogen‐containing bases: adenine, guanine, cytosine, and thymine. Adenine and guanine are purines, meaning that they are double ringed. On the other hand, cytosine and thymine (and Uracil in RNA) are pyrimidine, meaning that they are single ringed. In 1950, Chargaff found that the four bases are found in all organisms but the proportion varied from one to another. He realized that in the DNA of every organism, the amount of adenine was similar to the amount of thymine, and the amount of guanine was similar to the amount of cytosine. This was the beginning of Chargaff’s rules, stating that A = T and G = C. Later on, Watson and Crick’s DNA model explained the theory behind Chargaff’s rules. From looking at the x‐ray picture of DNA, Watson and Crick had enough clues to infer that the DNA is a helix with two strands that have a constant width apart. While making the model, they realize that the purine bases are twice as large as pyrimidine bases; therefore, they must pair up with each other to keep a regular width apart. They concluded that the DNA is a three dimensional double helix with the strands complementary to each other. The base‐pairing rule states that A and T always pair together and that G and C always pair together, due to their sizes and ability to form hydrogen bonds with another. The DNA Replication is during the Synthesis (S) stage. It is basically copying information from a single chromatid, and making another identical chromatid, which becomes two sister chromatids. DNA RNA Transcription Protein Translation The DNA helicase stimulates the unzipping of the nucleotide base pairs (places along the chromosome. The hydrogen bonds are broken and the bases on each strand are exposed to act as a template for the new set. Free nucleotides pair with the bases exposed as the template strands unzips. DNA polymerases bond these together to form new strands. As a result, there are two identical molecules of DNA, each with one strand from the original molecule and one new strand. DNA replication is semiconservative as one old strand is conserved, one new strand is made, and finally, combined together to form one DNA molecule. Transcription is copying the sequence of DNA (A, T, G, C) to produce an identical strand of mRNA gene that is later translated into a sequence of amino acids that create protein. For most eukaryotic cells, transcription occurs inside the nucleus. During or soon after it is finished, the mRNA exits through the membrane pores and translation happens in the cytoplasm. The mRNA is only made when the cell needs that particular segment of the DNA, allowing the cell to adjust in different demands. As replication begins, transcription is beginning as well by RNA polymerase. RNA polymerase recognizes transcription start site of gene and transcription complex (of RNA polymerase and other proteins) begins to unwind segments of DNA until the strands are apart from each other. RNA polymerase binds to the promoter region of the DNA strand and the factors encourage the start of transcription. It strings together an identical strand of mRNA nucleotides, using one strand of DNA as template (A with U, C with G) strand with the same base pairing system as replication. The growing RNA strand hangs freely until it is detached, as DNA helix zips back together in shape. Unlike DNA, mRNA has oxygen in ribose, which keeps it from being double stranded. Deoxyribose doesn’t have oxygen, allowing the two strands to connect. Also, adenine pairs with uracil instead of thymine in mRNA. Translation is a process that converts an mRNA message to a polypeptide that make up protein. A codon is a genetic unit of a three‐nucleotide sequence, which is coded for one amino acid. This process happens in the cytoplasm of the cell and takes a lot of energy. Before it actually starts, the small ribosomal subunit binds to the mRNA strand. The exposed codon attracts a complementary tRNA molecule bearing an amino acid and the tRNA anticodon pairs with the mRNA codon. The ribosome pulls the mRNA strand through itself one codon at a time. As the strand moves, the start codon and its complementary tRNA molecule shifts into the second site (P site) inside the large subunit. The ribosome also helps form a peptide bond between two amino acids and breaks the bond between tRNA molecule and amino acid. The tRNA that entered from A site moves to P site, leaving A site open. This exposes the next mRNA codon and the process continues as another complementary tRNA molecule is attracted to the exposed mRNA codon. The tRNA in the P site now moves to E (exit) site, and the tRNA exits the ribosome to be charged with another amino acid in the cytoplasm. The ribosome moves down the mRNA strand while attaching new amino acids to the growing protein, until it reaches a stop codon. The ribosome and protein are both released. Sickle cell anemia is a dangerous illness caused from a single change in a single nucleotide. According to Peachey, these blood cells have an irregular shape and only last for half of what its supposed to live. During replication, a point mutation can occur when an incorrect base is substituted during base substitution. A single base substitution can lead to many serious consequences such as the sickle cell anemia. If tautomeric shift occurs during base pairing, things such as adenine bonding with cytosine could happen. This small change in the nucleotide will affect the mRNA, as it will be created off the incorrect template. This will result in a change in a codon that leads to a different amino acid in the protein. Like mentioned in the worksheet, a single incorrect codon that led to an incorrect amino acid in the protein can cause the formation of things such as sickle cell anemia. In the case of sickle cell anemia, Peachey mentions, “The sixth DNA triplet, CTC, has been changed to CAC (the nitrogenous base thymine is replaced by adenine in the mutant gene)” (para. 4). Normally, the amino acid would be glutamic acid, which is very hydrophilic. However, the because of the mutation, the amino acid is now valine, which is very hydrophobic. As a result, it causes the shape of the blood cells to change into “stiff rod‐like structure”. This shape no longer allows the hemoglobin to load and unload oxygen properly. Abnormal hemoglobin leads to sickling of red blood cells. This causes rapid destruction of sickled cells, clumping of cells and interference with blood circulation, and collection of sickle cells in the spleen. This at the end could lead to: • Skull deformation • Weakness and fatigue • Impaired mental fuction • Poor physical development • Heart failure • Pneumonia • Rheumatism • Paralysis • Abdominal pain • Kidney failure (Based on diagram from Peachey, R. Sickle‐Cell Anemia: Example of a "Beneficial Mutation"?) Bibliography Peachey, R. (n.d.). Sickle‐Cell Anemia: Example of a "Beneficial Mutation"? Retrieved November 19, 2012, from Creation Science Association of British Columbia: http://www.creationbc.org/index.php?option=com_content&view=article&i d=113 &Itemid= Johnson, G., Ph.D., & Raven P., Ph.D. (2006). Biology. Orandlo, Fl., Holt, Rinehart and Winston.