BIO/CSC295 2009F, Class 06: Gene Alignments (1) Admin: * Grinnell HS Homecoming is this Thursday. If you've never seen a small-town homecoming parade, it's worth a gander. * The on your own exercise for chapter 2 is due next Tuesday. * Reading (and response) for Thursday: The BLAST paper. We'll understand if you can't grok it as deeply as the typical biology (or CS) paper. * Yes, Chapter 3 is also dense. We'll talk about Needleman-Wunsch (which almost no one gets at first or second glance) next Tuesday. * Try out for the play ("As You Like It" by this Shakespeare guy) * If you're an extra, you get to hang out with the cast and try to teach them BLAST. Overview: * An introduction to gene alignment (a biological perspective). * Lab for 2.5, continued. Sam's notes on Vida's presentation on chapter 3 * Trying to look at key biological issues in the chapter * The chapter is about how we align sequences * One of the earliest and most significant computational tools introduced to bioinformatics * As we started to gather sequence data, it became useful to compare * First projects on model systems * E. Coli and other bacteria * Yeast genome - Single cell eucaroyte * C. elegans - Worm * Drosophilia - Fly * Arabidopsis - Plant * Mouse - Animal * Helped us build technologies (sequencing, robotic, computational) to help with human genome project * Human genome project came in ahead of schedule and under budget. Why do we care about comparing sequences? * Student answer: Find relationships between genes in different "places" (organisms) * A tool for understanding evolutionary relationships * Student answer: Differences are interesting, too * How has the same gene changed in different species? * What does that tell us about gene function? * What does that tell us about the roles of different parts of the gene? * Conserved domains in proteins indicate to us that certain parts are important (have a functional consequence) * Student answer: Unless you can do some alignment, you can't necessary put everything back together * We need to connect overlapping pieces (Sequence Assembly) * Student answer: Identify plasmids that give resistance to antibiotics * Note from Vida: Looking at how geneomes evolved * Yeast has a duplicate genome, and then it evolved. (And Sam probably got that note wrong.) * Student answer: You can potentially identify unknown genes from similarity to known gene. * That is, you can get some information about expected function * Since IRBs are reluctant to let us do experiments on humans (and it takes a long time), we can find out about similar genes in other organisms and then predict back to humans. * "Guess what the Prof is thinking" answer: Think about the human genome project. Is it *the* human DNA? No, we're not clones. * We're genetically unique * For profquotes: "You are all winners at conception" (and birth) * Find out what *your* DNA says Some details about antibiotic bacteria and antibiotic resistance * Side note: 90% of our cells are bacteria (gut, skin, etc.) * It's not weight or mass. * Until this century, many people died from bacterial infection * Bacteria use our bodies as hosts, reproduce, and kill you * But it can't kill you too quickly, or it won't spread * Diarrhea helps bacteria spread quickly, as they get into the water supply * Some genes in our genome seem to have been selected b/c they support bacterial resistance * Side note: Allelle that makes you resistant to ___ virus also makes you more succeptable to West nile * In 1929, Fleming identified a fungus that produced an antimicrobial agent (that we call penicllin) * Lots of research to efficiently get penicillin * Rare enough at first that they would harvest the urine of those treated with penicillin and then re-extract the penicillin * A variety of Nobel prizes related to penicillin * Fleming * The woman who figured out the crystal structure * A few more people who helped in designing the technology to mass-produce. * Okay, what happens when we apply penicillin to a colony of bacteria? * Most die * A few, somewhat resistant ones, survive * Bacteria duplicate quickly * These bacteria don't have a lot of competition * So you get a *lot* of resistant bacteria * What does Erythromycin do? * Binds to ribosome * Prevents creation of protein * So, if you change the ribosome a bit (gene ermB), it may not bind * With any antibiotic, the regular bodily defense systems also helps. * You want to take the full course of antibiotic to kill as much as you can, including partially resistant * You hope the body takes care of the rest * Danger! Antibiotics invoke SOS responses in bacteria: Higher rate of mutation. Next issue: Vertical transfer takes some time, so how do we get so much transmission? Horizontal transfer? * Transduction: Bactorial sex: Create a bridge in which DNA gets transferred * Viruses * Bacteria take up DNA from env.