Current Topics in Computer Science: Computational GenomicsMolecular Biology PrimerLife begins with CellAll Life depends on 3 critical moleculesAll 3 are specified linearlyCentral Dogma of Biology: DNA, RNA, and the Flow of InformationDNAOverview of organizations of lifeSome TerminologyNucleic Acid ComponentsSlide 12DNA, continuedBasic StructureDNA, continuedDNA: the building blocks of genetic materialMUtAsHONSThe Good, the Bad, and the SilentGenetic VariationDNA - replicationDNA: The Code of LifeHuman chromosomesChromosomesDefinition of a GeneCentral Dogma RevisitedDNA: The Basis of LifePacking it inPacking it in IIPacking it in IIISuperstructureSuperstructure ImplicationsTranscriptional RegulationRNARNA (ribonucleic acid)Types of RNATerminologyTranscriptionDNA  RNA: TranscriptionTranscription, continuedTranscription: DNA  hnRNASlide 41Slide 42SplicingSplicing (Eukaryotes)RNA secondary structuresGenomic InformationProteinsProteins: Workhorses of the CellSlide 49Uncovering the codeTranslationSlide 52RNA  Protein: TranslationSlide 54Purpose of tRNASlide 56Slide 57Translation, continuedThe Central Dogma (revisited)Protein Synthesis: SummaryPolypeptide v. ProteinProtein FoldingSlide 63Protein folding – secondary structureSlide 65Protein Folding (cont’d)www.bioalgorithms.infoAn Introduction to Bioinformatics AlgorithmsCurrent Topics in Computer Science: Computational Genomics CSCI 7000-005Debra [email protected] Introduction to Bioinformatics AlgorithmsMolecular Biology PrimerAngela Brooks, Raymond Brown, Calvin Chen, Mike Daly, Hoa Dinh, Erinn Hama, Robert Hinman, Julio Ng, Michael Sneddon, Hoa Troung, Jerry Wang, Che Fung YungAn Introduction to Bioinformatics Algorithms www.bioalgorithms.infoLife begins with Cell•Smallest structural unit of an organism that is capable of functioning independently•All cells have some common featuresAn Introduction to Bioinformatics Algorithms www.bioalgorithms.infoAll Life depends on 3 critical molecules•DNA•Holds information on how cell works•RNA•Transfers short pieces of information to different parts of cell•Provides templates to synthesize into protein•Protein•Form enzymes that send signals to other cells and regulate gene activity•Form body’s major components (e.g. hair, skin, etc.)An Introduction to Bioinformatics Algorithms www.bioalgorithms.infoAll 3 are specified linearly•DNA and RNA are constructed from nucleic acids (nucleotides) •Can be considered to be a string written in a four-letter alphabet (A C G T/U) •Proteins are constructed from amino acids •Strings in a twenty-letter alphabet of amino acidsAn Introduction to Bioinformatics Algorithms www.bioalgorithms.infoCentral Dogma of Biology: DNA, RNA, and the Flow of Information TranslationTranscriptionReplicationwww.bioalgorithms.infoAn Introduction to Bioinformatics AlgorithmsDNAAn Introduction to Bioinformatics Algorithms www.bioalgorithms.infoOverview of organizations of life•Genes = books•Chromosomes = bookshelves•Nucleus = library•Almost every cell in an organism contains the same sets of books.•Books represent all the information (DNA) that every cell in the body needs so it can grow and carry out its various functions.An Introduction to Bioinformatics Algorithms www.bioalgorithms.infoSome Terminology•Gene •basic physical and functional units of heredity. •located on chromosomes•specific sequences of DNA bases that encode instructions on how to make proteins. •Genome•an organism’s genetic material, complete set of DNA.•a bacteria contains about 600,000 DNA base pairs•human and mouse genomes have some 3 billion.An Introduction to Bioinformatics Algorithms www.bioalgorithms.infoNucleic Acid Components•Nitrogenous Base: N is important for hydrogen bonding between bases A – adenine with T – thymine (double H-bond)C – cytosine with G – guanine (triple H-bond)•Sugar: Ribose (5 carbon)Base covalently bonds with 1’ carbonPhosphate covalently bonds with 5’ carbonNormal ribose (OH on 2’ carbon) – RNAdeoxyribose (H on 2’ carbon) – DNA dideoxyribose (H on 2’ & 3’ carbon) – used in DNA sequencing•Phosphate:negatively chargedAn Introduction to Bioinformatics Algorithms www.bioalgorithms.info The Purines The PyrimidinesAn Introduction to Bioinformatics Algorithms www.bioalgorithms.infoDNA•Stores all information of life•4 “letters” base pairs. AGTC (adenine, guanine, thymine, cytosine ) which pair A-T and C-G on complimentary strands.http://www.lbl.gov/Education/HGP-images/dna-medium.gifAn Introduction to Bioinformatics Algorithms www.bioalgorithms.infoDNA, continuedPhosphateBase (A,T, C or G)http://www.bio.miami.edu/dana/104/DNA2.jpgSugarAn Introduction to Bioinformatics Algorithms www.bioalgorithms.infoBasic StructurePhosphateSugarAn Introduction to Bioinformatics Algorithms www.bioalgorithms.infoDNA, continued•DNA has a double helix structure. However, it is not symmetric. It has a “forward” and “backward” direction. The ends are labeled 5’ and 3’ after the Carbon atoms in the sugar component. 5’ AATCGCAAT 3’3’ TTAGCGTTA 5’DNA always reads 5’ to 3’ for transcription replicationAn Introduction to Bioinformatics Algorithms www.bioalgorithms.infoDNA: the building blocks of genetic material•DNA provides a code, consisting of 4 letters, for all cellular function.An Introduction to Bioinformatics Algorithms www.bioalgorithms.infoMUtAsHONS•The DNA can be thought of as a sequence of the nucleotides: C,A,G, or T.•What happens to genes when the DNA sequence is mutated?An Introduction to Bioinformatics Algorithms www.bioalgorithms.infoThe Good, the Bad, and the Silent•Mutations can serve the organism in three ways:•The Good :•The Bad :•The Silent:A mutation can cause a trait that enhances the organism’s function:Mutation in the sickle cell gene provides resistance to malaria.A mutation can cause a trait that is harmful, sometimes fatal to the organism:Huntington’s disease, a symptom of a gene mutation, is a degenerative disease of the nervous system.A mutation can simply cause no difference in the function of the organism.Campbell, Biology, 5th edition, p. 255An Introduction to Bioinformatics Algorithms www.bioalgorithms.infoGenetic Variation•Despite the wide range of physical variation, genetic variation between individuals is quite small.•Out of 3 billion nucleotides, only roughly 3 million