An Introduction to Bioinformatics Algorithms www.bioalgorithms.info An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Outline: Molecular Biology Primer 1. How molecular biology came about? 2. Similarities: What is life made of? 3. Differences: Variation in genomes 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 Edited for Introduction to Bioinformatics (Autumn 2006) by Esa Pitkänen http://www.cs.helsinki.fi/mbi/courses/06-07/itb/ 8.9.2006 Introduction to Bioinformatics (Autumn 2006) 2 An Introduction to Bioinformatics Algorithms www.bioalgorithms.info An Introduction to Bioinformatics Algorithms www.bioalgorithms.info 1. How Molecular Biology came about? Major events in the history of Molecular • Microscopic biology began in • Robert Biology 1800 - 1870 1665 Hooke • 1865 Gregor Mendel discover the basic rules of • Robert Hooke (1635-1703) heredity of garden pea. discovered organisms are • An individual organism has made up of cells two alternative heredity units for a given trait ( dominant Mendel: The Father of Genetics trait v.s. recessive trait ) • Matthias Schleiden (1804- 1881) and Theodor Schwann (1810-1882) further • 1869 Johann Friedrich expanded the study of cells Miescher discovered DNA in 1830s • Theodor and named it nuclein. • Matthias Johann Miescher Schleiden Schwann 8.9.2006 Introduction to Bioinformatics (Autumn 2006) 3 8.9.2006 Introduction to Bioinformatics (Autumn 2006) 4 An Introduction to Bioinformatics Algorithms www.bioalgorithms.info An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Major events in the history of Molecular Major events in the history of Molecular Biology 1880 - 1900 Biology 1900-1911 • 1881 Edward Zacharias showed chromosomes are • 1902 - Emil Hermann Fischer wins Nobel prize: showed amino acids are linked and form composed of nuclein. proteins • Postulated: protein properties are defined by Emil amino acid composition and arrangement, which Fischer • 1899 Richard Altmann renamed nuclein to nucleic acid. we nowadays know as fact • By 1900 , chemical structures of all 20 amino acids had • 1911 – Thomas Hunt Morgan discovers genes on chromosomes are the discrete units of • been identified heredity Thomas Morgan • 1911 Pheobus Aaron Theodore Lerene discovers RNA 8.9.2006 Introduction to Bioinformatics (Autumn 2006) 5 8.9.2006 Introduction to Bioinformatics (Autumn 2006) 6 1 An Introduction to Bioinformatics Algorithms www.bioalgorithms.info An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Major events in the history of Molecular Major events in the history of Molecular Biology 1940 - 1950 Biology 1950 - 1952 • 1941 – George Beadle and • 1950s – Mahlon Bush Edward Tatum identify that genes Hoagland first to isolate tRNA make proteins Mahlon Hoagland George Edward Beadle Tatum • 1950 – Edwin Chargaff find Cytosine complements Guanine • 1952 – Alfred Hershey and and Adenine complements Martha Chase make genes Thymine Edwin from DNA Chargaff Hershey Chase Experiment 8.9.2006 Introduction to Bioinformatics (Autumn 2006) 7 8.9.2006 Introduction to Bioinformatics (Autumn 2006) 8 An Introduction to Bioinformatics Algorithms www.bioalgorithms.info An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Major events in the history of Molecular Major events in the history of Molecular Biology 1952 - 1960 Biology 1970 • 1970 Howard Temin and David • 1952-1953 James D. Baltimore independently isolate Watson and Francis H. C. James Watson the first restriction enzyme Crick deduced the double and Francis Crick helical structure of DNA • DNA can be cut into reproducible pieces with site-specific endonuclease • 1956 George Emil Palade called restriction enzymes; showed the site of enzymes • the pieces can be linked to manufacturing in the bacterial vectors and cytoplasm is made on RNA introduced into bacterial hosts. organelles called ribosomes. (gene cloning or recombinant George Emil Palade DNA technology ) 8.9.2006 Introduction to Bioinformatics (Autumn 2006) 9 8.9.2006 Introduction to Bioinformatics (Autumn 2006) 10 An Introduction to Bioinformatics Algorithms www.bioalgorithms.info An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Major events in the history of Molecular Major events in the history of Molecular Biology Biology 1970- 1977 1986 ---1995 • 1986 Leroy Hood: Developed automated sequencing • 1977 Phillip Sharp and mechanism Richard Roberts demonstrated that pre-mRNA • 1986 Human Genome Initiative Leroy Hood announced is processed by the excision Phillip Sharp Richard Roberts of introns and exons are • 1990 The 15 year Human spliced together. Genome project is launched by congress • Joan Steitz determined that • 1995 Moderate-resolution maps the 5’ end of snRNA is of chromosomes 3, 11, 12, and partially complementary to 22 maps published (These maps provide the locations of the consensus sequence of “markers” on each chromosome 5’ splice junctions. Joan Steitz to make locating genes easier) 8.9.2006 Introduction to Bioinformatics (Autumn 2006) 11 8.9.2006 Introduction to Bioinformatics (Autumn 2006) 12 2 An Introduction to Bioinformatics Algorithms www.bioalgorithms.info An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Major events in the history of Molecular Biology Major events in the history of Molecular Biology 19951995----19961996 1997 ---1999 • 1995 John Craig Venter: First • 1997 E. Coli sequenced bactierial genomes sequenced • 1998 PerkinsElmer, Inc.. Developed 96-capillary • 1995 Automated fluorescent sequencer sequencing instruments and John Craig Venter robotic operations • 1998 Complete sequence of the Caenorhabditis elegans genome • 1996 First eukaryotic genome- yeast-sequenced • 1999 First human chromosome (number 22) sequenced 8.9.2006 Introduction to Bioinformatics (Autumn 2006) 13 8.9.2006 Introduction to Bioinformatics (Autumn 2006) 14 An Introduction to Bioinformatics Algorithms www.bioalgorithms.info An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Major events in the history of Molecular Biology Major events in the history of Molecular Biology 20002000----20012001 20032003----Present • 2000 Complete sequence • April 2003 Human Genome of the euchromatic portion Project Completed. Mouse of the Drosophila genome is sequenced. melanogaster genome • April 2004 Rat genome sequenced. • 2001 International Human Genome Sequencing :first draft of the sequence of the human genome published 8.9.2006 Introduction to Bioinformatics (Autumn 2006) 15 8.9.2006 Introduction to Bioinformatics (Autumn 2006) 16 An Introduction to Bioinformatics Algorithms www.bioalgorithms.info An Introduction to Bioinformatics Algorithms www.bioalgorithms.info 2. What is Life made of? 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 are descended from the same primitive cell. • All prokaryotic and eukaryotic cells are the result of a total of 3.5 billion years of evolution. 8.9.2006 Introduction to Bioinformatics (Autumn 2006) 17 8.9.2006 Introduction to Bioinformatics (Autumn 2006) 18 3 An Introduction to Bioinformatics Algorithms www.bioalgorithms.info An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Cells Life begins with Cell • Chemical composition -by weight • 70% water • 7% small molecules • salts • Lipids • amino acids • nucleotides • 23% macromolecules • Proteins • Polysaccharides • A cell is a smallest structural unit of an • lipids organism that is capable of independent • biochemical (metabolic) pathways functioning • translation of mRNA into proteins • All cells have some common features 8.9.2006 Introduction to Bioinformatics (Autumn 2006) 19 8.9.2006 Introduction to Bioinformatics (Autumn 2006) 20 An Introduction to Bioinformatics Algorithms www.bioalgorithms.info An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Common features of organisms All Cells have common Cycles • Chemical energy is stored in ATP • Genetic information is encoded by DNA • Information is transcribed into RNA • There is a common triplet genetic code • Translation into proteins involves ribosomes • Shared metabolic pathways • Similar proteins among diverse groups of organisms • Born, eat, replicate, and die 8.9.2006 Introduction to Bioinformatics (Autumn 2006) 21 8.9.2006 Introduction to Bioinformatics (Autumn 2006) 22 An Introduction to Bioinformatics Algorithms www.bioalgorithms.info An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Two types of cells: Prokaryotes and Prokaryotes and Eukaryotes 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 are kingdom Eukarya and includes plants, animals, fungi and certain algae. 8.9.2006 Introduction to Bioinformatics (Autumn 2006) 23 8.9.2006 Introduction to Bioinformatics (Autumn 2006) 24 4 An Introduction to Bioinformatics Algorithms www.bioalgorithms.info An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Prokaryotes and Eukaryotes, Signaling Pathways: Control Gene continued Activity Prokaryotes Eukaryotes • Instead of having brains, cells make decision Single cell Single or multi cell through complex networks (or pathways) of No nucleus Nucleus chemical reactions • Synthesize new materials No