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Introduction to molecular biology, continued Adding to complexity of the biosphere * Each multicellular organism has different kinds of cells with different gene/protein repertoires * At least 1.7 million (!) species/organisms, each with different gene/protein repertoires Introduction to molecular biology * DNA molecule as carrier of genetic information * Gene technology * Flow of genetic information * Complexity of the biological world. * Kingdoms of life - overview of life forms * Evolution - principles and mechanisms 1 Organisms are remarkably uniform at the molecular level This uniformity reveals that organisms on Earth have arisen from a common ancestor The three kingdoms of life Eukarya (eukaryotes) Nucleus. All multicellular organisms , like animals and plants. Some single-celled organisms like yeast. Bacteria (eubacteria) No nucleus. Single-celled. Ubiquitous. Archaea (archaebacteria) No nucleus. Single-celled. Certain properties shared with Eukarya. Live in extreme environments (like high temperature or high salt) Bacteria+Archaea are also called prokaryotes 2 Archaea live in extreme environments 3 Tree of life and the three kingdoms of life Viruses - dependent on living cells for propagation HIV 4 HIV genome Introduction to molecular biology * DNA molecule as carrier of genetic information * Gene technology * Flow of genetic information * Complexity of the biological world. * Kingdoms of life - overview of life forms * Evolution - principles and mechanisms 5 Principles of evolution Reproduction Variation Competition/selective pressure Variation comes from mutations : changes in base sequence of DNA 1) single nucleotide change (point mutation) A->T, T->G , etc 2) insertion / deletion of one or several nucleotides Such mutations are the result of Replication errors Chemicals & irradiation 6 Mutations, cont. 3) Homologous recombination cause large rearrangements in the genome. New gene families arise by gene duplication and divergence Tree of life and the three kingdoms of life 7 Why do we bother with evolution in bioinformatics? * We are in experimental biology making use of many model organisms that are evolutionary related to human * An extremely common task in bioinformatics is to examine evolutionary related sequences. (BLAST) * Comparative genomics can be used to identify biologically significant elements 8 Bioinformatics The application of CS and math in the handling and analysis of data resulting from modern gene technology. Human genome 3 x 109 base pairs What are the bioinformatics challenges - what can we learn from the sequence? 9 Example 1: Prediction of genes in the human genome Genome The complete genetic material of an organism Gene a portion of a DNA molecule that contains all the information for production of a protein 10 Example 2 : Bioinformatics aids in predicting the molecular basis of disease BRCA1 gene - genetic factor in breast cancer Cloning and sequencing of the gene revealed a protein remotely related to a yeast protein (Rad9) involved in cell cycle control RAD9_YEAST : GNVFDKCIFVLTS-LFENReELRQTIESQGGTVIeSGfstlfnfthplakslvnkgntdn BRC1_HUMAN : ERVNKRMSMVVSGLTPEEFmLVYKFARKHHITLTnLI----------------------- RAD9_YEAST : irelalklawkphslfaDCRFACLITKRHLrSLKYLET------LALGWPTLHWKFISAC BRC1_HUMAN : -----------------TEETTHVVMKTDA-EFVCERTLKyflGIAGGKWVVSYFWVTQS RAD9_YEAST : IEKKRIVPHLIYQY BRC1_HUMAN : IKERKMLNEHDFEV Example 3: Analysis of the human genome reveals a large number of olfactory receptor proteins 11 Example 4: Sequence analysis is essential in phylogenetic studies Human evolution Origin of man Closest primate relatives of man? Did modern humans originate in Africa? Relationship between human populations Evolution of viruses / microorganisms that cause human disease HIV (AIDS) H5N1 (Bird Flu) Example 5: Protein structure prediction and structural bioinformatics is important for our understanding of biology and is essential in the development of drugs HIV protease 12