Science Section III: Molecular Genetics Pages 54-64

1. Science Section III:Molecular GeneticsPages 54-64 Wendy Nguyen Sept. 3, 2013

2. Objectives: • The Identification of DNA as the Genetic Material • The Cracking of the Genetic Code • Franklin’s Contribution • Watson and Crick • The Organization of DNA • The Genetic Code • The Basic Rules of DNA Replication • Semi-Conservative DNA Replication • Mutation

3. The Identification of DNA as the Genetic Material • When the flu pandemic had subsided, millions of people died, primarily from bacterial infections, as their bodies’ defense systems became weak from fighting the influenza virus. • Streptococcus pneumoniae was the bacterium responsible for most of the deaths. • Through clinical research of the bacterium, it led the discovery of DNA as the genetic material. • Per Oswald Avery, DNA was a “transforming substance” enriched with nucleic acids • Per Frederick Griffin, there were 2 different strains of bacterium that led him to believe that DNA is the “transforming principle” • Per Hershey and Chase, bacteriophage occurs when a virus infects a bacteria thus changing the genetic makeup of DNA

4. The Cracking of the Genetic Code - Franklin’s Contribution • Rosalind Franklin isolated the DNA crystal to produce a 3-D, double-stranded twisted-ladder image of the DNA molecule. • X-ray crystallography – a technique using x-ray to produce a shadow image of a molecule, which provides information regarding the size, shape, and spatial relationship of certain key components • The image suggested that sugar and phosphate form the backbone of the two DNA strands and the nitrogenous bases are locate near the center of the two strands • Franklin’s contribution provided the foundation that later constructed the DNA model.

5. The Cracking of the Genetic Code - Watson and Crick • James Watson and Francis Crick introduced the famous double helix model of DNA • Deoxyribose and phosphate form the two backbones (strands) with the complementary bases (A pairs with T; C pairs with G) held together by hydrogen bonds

6. The Organization of DNA • Eukaryotic DNA is highly diverse in structure and organization. It consists of a nucleus with multiple linear chromosomes located within. • Majority of eukaryotes have two copies of each chromosomes from each parent through sexual reproduction. • The human genome has an estimate of 3.1 billion nucleotides; however, about 22,000 genes we have are not coded from our genome. • For a typical gene, there are intervening events of introns with exons. • Introns – noncoding regions • Exons– coding regions; are part of the mRNA used to make a specific functional protein

7. The Organization of DNA -The Genetic Code • A language of nucleotides where information is stored in the DNA molecule • Composed of 4 letters: A, T, G, and C • These 4 letters are arranged as triplets – each set is defined as a codon in the mRNA • i.e.: AUG, CCA, GGG • Maximum number of 64 codons • Only 20 codons are used for protein synthesis, where each amino acid is coded for by more than one codon (except UGG, which only codes for tryptophan). • Stop codons– UAA, UAG, and UGA do not code for any amino acids where they signal the cell to terminate translation • Start codon– AUG signals the start of protein synthesis or translation, and it also codes for the amino acid methionine

8. The Basic Rules of DNA Replication –Semi-Conservative DNA Replication • Semi-conservative DNA Replication: the double-stranded DNA helix is replicated, each new double-stranded DNA is composed of one strand from the original helix and one newly synthesized strand of DNA • DNA replication consists of a highly coordinated and regulated process involving more than a dozen enzymes and other proteins that adjust the on/off switch regulating DNA function. • Replication in eukaryotes take place simultaneously at multiple sites. • Some of the following enzymes: • 1. Helicase (“unzipper”) – unzips a portion of the DNA double helix at the starting point to create a replication fork and then a replication bubble; the unzipped DNA strand is protected by proteins to prevent the strands from reconnecting into the double helix.

9. The Basic Rules of DNA Replication –Semi-Conservative DNA Replication • Some of the following enzymes: • 2. Primase– creates and attaches RNA primers to the replicating strands; the RNA primer is a short segment of RNA that initiates the process of DNA replication • 3. DNA polymerases (“builders” and “proofreaders”) – are multiple enzymes complexes that continuously add complementary nucleotides to the leading stand of one daughter DNA strand in the right direction; other (lagging) daughter strand is added piece by piece • 4. Nucleases (“editors”) – detects incorrect nucleotides and removes them • 5. DNA ligase (“zipper”) – adds phosphate in the remaining gap of the backbone; joins the new DNA fragment to the parent DNA template

10. Mutation • A mutation is defined when an organism’s DNA is damaged, resulting in the possibility that genes can become altered. • It can be lethal in terms of a rare cancer gene, or considered as the “junk” gene portion where it is tolerable. • Mutation can also be a source of evolution thus the formation of new species. • Can occur randomly during DNA replication. Metabolic and/or environmental products can also increase the risk for mutation.

11. Mutation • Mutations are classified based on the alterations of the amino acid sequence: • Missense – when the amino acid being coded for is changed by a nucleotide substitution • Nonsense – when a substitution causes a stop condon • e.g., ACC  becomes ATC  which codes for UAG = a stop codon • Frameshift– when one nucleotide is added or deleted, causing a shift in the triplet to all downstream codons; causes dramatic changes in the amino acid sequence

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