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Molecular Biology Primer

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Molecular Biology Primer An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Molecular Biology Primer Angela Brooks, Raymond Brown, Calvin Chen, Mike Daly, Hoa Dinh, Erinn Hama, Robert Hinman, Julio Ng, Michael Sneddon, Hoa Troung, Jerry Wang, Che Fung Yung An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Outline 0. A Brief History of Molecular Biology 1. The Fabric of Life 2. What Is Genetic Material? 3. What Do Genes Do? 4. What Molecule Codes For Genes? 5. What Is the Structure Of DNA? 6. Information Transfer Between DNA and Proteins 7. How are Proteins Made? An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Outline 8. How Can We Analyze DNA? 1. Copying DNA 2. Cutting and Pasting DNA 3. Measuring DNA Length 4. Probing DNA 9. How Do Individuals of a Species Differ? 10. How Do Species Differ? 1. Molecular Evolution 2. Comparative Genomics 3. Genome Rearrangement 11. Why Bioinformatics? An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Section 0: A Brief History of Molecular Biology An Introduction to Bioinformatics Algorithms www.bioalgorithms.info A Brief History of Molecular Biology • 1665: Robert Hooke (1635-1703) discovers organisms are made up of cells. Robert Hooke • 1830s: Matthias Schleiden (1804-1881) and Theodor Schwann (1810-1882) further expanded the study of cells. Matthias Schleiden Theodor Schwann An Introduction to Bioinformatics Algorithms www.bioalgorithms.info A Brief History of Molecular Biology • 1865: Gregor Mendel discovers the basic rules of heredity for the garden pea. • An individual organism has two alternative heredity units for a given Mendel: The Father of Genetics trait (dominant trait vs. recessive trait). • 1869: Johann Friedrich Miescher discovers DNA and names it “nuclein.” Johann Miescher An Introduction to Bioinformatics Algorithms www.bioalgorithms.info A Brief History of Molecular Biology • 1881: Edward Zacharias shows chromosomes are composed of nuclein. • 1899: Richard Altmann renames nuclein to “nucleic acid.” • 1900: Chemical structures of all 20 amino acids have been identified. An Introduction to Bioinformatics Algorithms www.bioalgorithms.info A Brief History of Molecular Biology • 1902: Emil Hermann Fischer wins Nobel prize: shows amino acids are linked and form proteins. • Postulates that protein properties are defined by amino acid composition and arrangement, which we now know is true. Emil Fischer • 1911: Thomas Hunt Morgan discovers that genes on chromosomes are the discrete units of heredity. • 1911: Pheobus Aaron Theodore Lerene discovers RNA. Thomas Morgan An Introduction to Bioinformatics Algorithms www.bioalgorithms.info A Brief History of Molecular Biology • 1941: George Beadle and Edward Tatum identify that genes make proteins. George Beadle Edward Tatum • 1950: Edwin Chargaff finds that cytosine complements guanine and adenine complements thymine. Edwin Chargaff An Introduction to Bioinformatics Algorithms www.bioalgorithms.info A Brief History of Molecular Biology • 1952: Alfred Hershey and Martha Chase make genes from DNA. Hershey Chase Experiment • 1952-1953: James D. Watson and Francis H. C. Crick deduce the double helical structure of DNA. James Watson & Francis Crick An Introduction to Bioinformatics Algorithms www.bioalgorithms.info A Brief History of Molecular Biology • 1956: George Emil Palade shows that the site of enzymes manufacturing in the cytoplasm is on RNA organelles called ribosomes. George Emil Palade • Late 1950s: Mahlon Bush Hoagland is first to isolate tRNA. Mahlon Bush Hoagland An Introduction to Bioinformatics Algorithms www.bioalgorithms.info A Brief History of Molecular Biology • 1970: Howard Temin and David Baltimore independently isolate the first restriction enzyme. • DNA can be cut into reproducible pieces with site- specific endonuclease called restriction enzymes. • The pieces can be linked to bacterial vectors and introduced into bacterial hosts. (This is called gene cloning or recombinant DNA technology). An Introduction to Bioinformatics Algorithms www.bioalgorithms.info A Brief History of Molecular Biology • 1977: Phillip Sharp and Richard Roberts demonstrate that pre-mRNA is processed by the excision of introns and exons are spliced together. Phillip Sharp Richard Roberts • Joan Steitz determines that the 5’ end of snRNA is partially complementary to the consensus sequence of 5’ splice junctions. Joan Steitz An Introduction to Bioinformatics Algorithms www.bioalgorithms.info A Brief History of Molecular Biology • 1986: Leroy Hood develops automated sequencing mechanism. • 1990: The 15 year Human Genome Project is launched by Congress. Leroy Hood • 1995: Moderate-resolution maps of chromosomes 3, 11, 12, and 22 maps are published (These maps provide the locations of “markers” on each chromosome to locate genes.) An Introduction to Bioinformatics Algorithms www.bioalgorithms.info A Brief History of Molecular Biology • 1995: John Craig Venter sequences first bacterial genomes. • 1995: Automated fluorescent sequencing instruments and robotic operations. John Craig Venter • 1996: The first eukaryotic genome (yeast) is sequenced. An Introduction to Bioinformatics Algorithms www.bioalgorithms.info A Brief History of Molecular Biology • 1997: E. Coli is sequenced. • 1998: PerkinsElmer, Inc. develop 96-capillary sequencer. • 1998: Caenorhabditis elegans (a type of roundworm) is sequenced. • 1999: The first human chromosome (number 22) is sequenced. An Introduction to Bioinformatics Algorithms www.bioalgorithms.info A Brief History of Molecular Biology • 2000: Complete sequence of the euchromatic portion of the Drosophila melanogaster (common fruit fly) genome. • 2001: International Human Genome Sequencing: first draft of the sequence of the human genome is published. An Introduction to Bioinformatics Algorithms www.bioalgorithms.info A Brief History of Molecular Biology • 2003: Human Genome Project completed. • 2003: Mouse genome is sequenced. • 2004: Rat genome is sequenced. An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Section 1: The Fabric of Life An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Section 1: The Fabric of Life An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Outline for Section 1 • Cells Make Up All Living Things • Prokaryotes vs. Eukaryotes • Cell Signaling • The Contents of the Cell: From DNA, to RNA, to Proteins An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Cells • Fundamental working units of every living system. • Every organism is composed of one of two radically different types of cells: prokaryotic cells or eukaryotic cells. • Prokaryotes and Eukaryotes have all evolved from the same primitive cell 3.5 billion years ago. An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Cells • Chemical composition—by weight: • 70% water • 7% small molecules: salts, lipids, amino acids, nucleotides • 23% macromolecules: proteins, polysaccharides, lipids • Biochemical (metabolic) pathways. • Translation of mRNA into proteins. An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Life Begins at the Level of the Cell • A cell is the smallest structural unit of an organism that is capable of functioning independently. • All cells share some common features. An Introduction to Bioinformatics Algorithms www.bioalgorithms.info All Cells Share Common Cycles • All cells are born, “eat,” replicate, and die. An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Two Types of Cells: Prokaryotes and Eukaryotes An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Prokaryotes vs. Eukaryotes • According to the most recent evidence, there are three main branches to the tree of life. • Prokaryotes include Archaea (“ancient ones”) and bacteria. • Eukaryotes form the kingdom Eukarya which includes plants, animals, fungi, and certain algae. An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Prokaryotes vs. Eukaryotes Prokaryotes Eukaryotes Single cell Single or multi cell No nucleus Nucleus No organelles Organelles One piece of circular DNA Chromosomes No mRNA post transcriptional Exons/Introns splicing modification An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Prokaryotes vs. Eukaryotes: Structural Differences Prokaryotes Eukaryotes • Eubacterial (blue-green algae) • Plants, animals, Protista, and and archaebacteria fungi • only one type of membrane— • complex systems of internal plasma membrane—forms membranes forms • the boundary of the cell proper • organelles and compartments • The smallest cells known are • The volume of the cell is bacteria several hundred times larger • Example: E. coli • Example: Hela cell 6 • 3x10 protein molecules • 5x109 protein molecules • 1000-2000 polypeptide species. • 5000-10,000 polypeptide species An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Prokaryotes vs. Eukaryotes: Chromosomes Prokaryotes Eukaryotes • The genome of E. coli contains • The genome of yeast cells 4 x 106 base pairs contains 1.35 x 107 base pairs • A small fraction of the total • > 90% of DNA encode proteins DNA encodes protein. • Many repeats of non-coding sequences • All chromosomes are contained • Lacks a membrane-bound in a membrane bound nucleus nucleus. • DNA is divided between two • Circular DNA and supercoiled or more chromosomes domain • A set of five histones • DNA packaging and gene expression regulation • Histones are unknown An Introduction to Bioinformatics Algorithms www.bioalgorithms.info
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