Molecular Biology What Is DNA and How Does It Work? DNA Structure Must Be Compatible with Its Four Roles • DNA makes copies of itself. – Occurs during S phase of the cell cycle before mitosis or meiosis. • DNA encloses information. – Information that gives rise to discernible traits in organisms. DNA Structure Must Be Compatible with Its Four Roles • DNA controls cells and tells them what to do. – Determines function of the cell. • DNA changes by mutation. – Structure must be able to change. Building Blocks of DNA • Nucleotides – Three components: • Five-carbon sugar • Phosphate group • Nitrogen-containing base Building Blocks of DNA • Four nitrogenous bases in DNA – – – – Adenine Thymine Guanine Cytosine Structure of DNA • Maurice Wilkins and Rosalind Franklin – Attempted to determine structure of DNA. – Discovered DNA was a helix. Chargaff’s Ratios • 1950 – Erwin Chargaff • Observed that the four nitrogenous bases conformed to a rule: – Amount of Adenine = Amount of Thymine – Amount of Cytosine = Amount of Guanine • Served as a clue to help Watson and Crick determine DNA structure! Watson and Crick • Early 1950s – They were young scientists at Cavendish Laboratory in Cambridge, England. • Using Chargaff’s ratios and Franklin’s data, Watson and Crick determine DNA structure is a double helix DNA Double Helix • Consists of two strands of nucleotides. • Nucleotides bonded together with covalent bonds. – Adenine hydrogen bonds with Thymine. – Cytosine hydrogen bonds with Guanine. • Structure was compatible with four roles of DNA How Does DNA Copy Itself? • DNA replication – Precedes cell division. – Process: • DNA strands separate • New complementary base pairs are added forming a new strand – Result: two double helices. • Each containing one old strand of DNA and one new strand of DNA Meselson and Stahl • Proved the mechanism of DNA replication. – Called semiconservative mechanism. • Grew bacteria in medium containing various radioactive nitrogen isotopes. – Separated DNA by density using a dense, viscous sugar solution. How is the information in DNA expressed? • Genome – Information to make proteins stored in all of the DNA of a single set of chromosomes. • Gene: blueprint for the synthesis of a protein. • Proteins – Polymers made of amino acids connected end-to-end • Similar to beads on a string. How is the information in DNA expressed? • Chromosomes containing DNA contained in nucleus. • DNA codes for the construction of proteins using an intermediary molecule: – Ribonucleic acid or RNA. • Decoding information in DNA requires two processes: – Transcription. – Translation. DNA vs. RNA • RNA: – Contains the sugar ribose. – Contains adenine, uracil, cytosine and guanine. – Single helix • DNA: – Contains deoxyribose. – Contains adenine, thymine, cytosine and guanine. – double helix. DNA vs. RNA • RNA: – Smaller, mobile. – Degrades easily. – Travels form nucleus to cytoplasm. • DNA: – Larger, immobile. – Lasts the life of cell. – Resides in nucleus. Types of RNA • Messenger RNA – Carries genetic information from DNA in nucleus to cytoplasm. • Information is used to synthesize a protein. – Codon: three nucleotide sequence that codes for one amino acid. Types of RNA • Transfer RNA – Functions as the “interpreter” – Transfer amino acids to the sites where the information in the mRNA is being used to make a protein – Anticodon: three nucleotide sequence that is complementary to a particular codon in mRNA Types of RNA • Ribosomal RNA – Combine with proteins to form ribosomes • Ribosomes – Site of translation – Large subunit – Small subunit Protein Synthesis • Two processes: – Transcription • Occurs in the nucleus • Produces RNA – Translation • Occurs in the cytoplasm • Produces proteins Transcription Translation • To line up the appropriate amino acids in the proper order requires: – mRNA – tRNA – Ribosomes Translation Translation • Codon (mRNA) must be complementary to the anticodon (tRNA). • Translation continues until ribosome encounters a stop codon. Genetic Code • Three nucleotides in mRNA (codon) code for one amino acid. • Some sequences serve as starting points. • AUG codes for the amino acid methionine which also indicates to start translation. • Some sequences do not have complementary tRNA. – Indicate to the ribosome to stop translation. Genetic Code What Makes Cells Different From Each Other? • Due to the information in the DNA, a cell could manufacture 50,000 different proteins, but it doesn’t. • The proteins a cell produces influences its function. – Example: red blood cells and hemoglobin Gene Expression • Some genes are always transcribed and translated. – Others can be turned on or off by environmental signals • Gene expression is highly regulated. Gene Expression in Prokaryotes • Jacob and Monod – Studied digestion of lactose in bacteria. – Discovered the lac operon. • Prokaryotes regulate gene expression at the level of transcription Gene Expression in Eukaryotes • Regulated at the level of transcription. – Transcription requires transcription factors. • They recognize and bind to DNA sequences called regulatory sequences • Transcription factors can increase or decrease the rate of transcription • Longevity of RNA molecule also influences gene expression. How Does DNA Change Over Time? • Mutations: a permanent change in the genetic material of a cell or organism. – Can be inherited. – Can involve whole chromosomes or changes in DNA sequences. Whole Chromosome Mutations • Polyploid: organism or cell containing three or more sets of chromosomes. – Occurs due to a cell division error. – Frequently seen in plants, rare in animals. – Can have advantageous results. Whole Chromosome Mutations • Nondisjunction: instances when paired chromosomes fail to separate during mitosis or meiosis – Can result in an aneuploid: individual whose chromosome number is greater or less than normal Whole Chromosome Mutations • Down’s Syndrome – Due to nondisjunction with chromosome 21. – Characterized by mental retardation, distinctive facial features. Whole Chromosome Mutations • Transposons: – Variety of DNA sequences that can randomly insert themselves by transposition in various non-homologous regions on chromosomes and other DNA. – Can generate new gene combinations – Can also induce genetic errors Mutations Involving Single DNA Nucleotides • Point Mutations: – Change in a single nucleotide base pair. – Example: sickle cell anemia. Mutations Involving Single DNA Nucleotides • Frame-shift mutation: – A change in the reading frame resulting from an insertion or deletion of nucleotides in the DNA sequence for a protein. – Extremely harmful. Normal: JOE ATE THE HOT DOG After deletion: JEA THE OTD OG