BIO/CSC295 2011F, Class 05: Gene Alignments (1) Overview: * Chapter 2 Programming Lab. * The Sequence Explosion. * Aligning Sequences: A Biological Perspective. * Bacteria and Antibiotic Resistance. Admin: * For Tuesday, respond to Altschul et al. 1990. This paper is particularly complex, so it's okay if you don't understand everything. * For Tuesday, start considering the Needleman-Wunsch algorithm. * On-Your-Own Project 2.6 is due next Thursday. DO THE PROJECT IN GROUPS! CONTINUE THE GRUOPS YOU HAVE TODAY. * Sam updated the office hours on the course front door. * EC for Teriak Koscik talk, Today, 4:30, Science 3821. * EC for Football, Saturday, 1 p.m. * EC for Les Duke, Saturday. * EC for Volleyball, Friday at 6 p.m., Saturday at Noon, 4 p.m. * EC for Men's Soccer, Sunday, 2pm, Coe. * EC for "Planning Grinnell's Future", 11 a.m., Sept. 15 * EC for Eckhart's Species Range "Hints of what my MAP students did", Friday, noon, Big Bio lecture room * Biology picnic Friday! * If you choose to participate in the '80's party, please don't try to replicate the excesses of the '80's. Lab: * Same groups as Tuesday! * Lots of "sketch the algorithm, read the code". Make sure to take the time to sketch the algorithmI Questions are "suppose you want to do this? How would you do it? Provide some code so you can see how it is done, using correct syntax. Quick Reflections from SamR: * Python is a new language, so you have to learn lots of things * Syntax: * No 'returns' in the middle of strings * Sometimes THING.FUNCTION(PARAMS) * Sometimes FUNCTION(THING,OTHERS) * Colons, colons, everywhere * Vocabulary: * len(___) gives the length of a string * str.find(pattern) gives the index of the first occurence of pattern * str[start:after] gives a substring * str[::-1] reverses a string * str.rev() * Even experienced programmers need to look things up (or ask) * Chase says "After you click the green "Run" button, check to see if there are errors before you do anything else." Detour: Portfolios * Due at end of semester (at final) * Three parts * A response of which you are proud, and a note on why you chose it * Some code of which you are proud, and a note on why you chose it * A note about what roles you served in your project group Chapter Three (3)! * Directed at thinking about sequence comparison The Sequence Explosion * Databases are chock-full-of-sequences * What were the first whole-genome sequences that appeared? * One of those great questions in which we don't know the answer * 1980's, probably E. Coli * Also virus genomes * Technology was primitive * Then lots of money thrown at the Human Genome Project * But sequenced "model" systems first * S. Cervesiae (sp) - Yeast * C. Elegans - Multicellular * D. Melanagaster - Flies * What is a model system? * Clarkia - A nice organism to study species ranges * Systems that lots of people use to study gene activity * So sequence data are already available * Why start with model systems before doing HuGePr? * They are simpler - less DNA! * You can do experiments on them. An independent way of confirming what you're doing. * Lots of mapping data - where genes appear on chromosome * If you know the waypoints, you can better connect things * As researchers went along, things got much much better * Biology techniques * Including robots for doing it * Computational techniques for positioning things * And computational power for doing that * So they could deal with much larger data sets * HuGePr came in EARLY and UNDER BUDGET * Recently, a company delivered 600 full individual human genomes for a research study in less than a month and for about $1K per person * HuGePr was much more expensive and longer * What is the power of having 600 people in the database? * Easier to dig out mutations that don't have phenotypic effects * Easier to correlate things * A diverse set of genomes can help you study things that might affect certain populations. * Whose Genome was sequenced in HuGePr? * NCBI says "Lots of donors, both men and women" * Rumours that it's Craig Ventner * Why should we protect the privacy of the person who is the ref sequence? * Once we start learning about the genes, your private medical info is out there. * Computationally: How do we compare sequences? * Sequence comparisons are complex * Mutations that do insertions and deletions Example of Large Sequence Comparisons: Antibiotic Resistance * What are antibiotics? * Chemical compounds that kill things, usually bacteria * Why do we care about bacteria? * E. Coli outbreak in Europe this summer ("It's on some food, we don't know what it is. Probably those evil spanish cucumbers. Maybe the GMO food. Maybe that hippie-dippie organic stuff.") * Some bacteria make people very sick. Some infections kill people. * Diarrheal diseases are second-leading cause of death in children (1.87 million deaths per year worldwide) * Also cause of malnutrition * A really important health problem * Until the advent of penicillin, bacterial infections were a huge cause of death. * Penicillin discovered by Fleming in 1928 * Many have been developed since them. * So deaths related to bacterial infections are really low * Surprising thing of European E. Coli outbreak: Antibiotics made things worse. * Antibiotics induce a stress response. Stress response releases poisons. * We've been 'fast and loose' with antibiotics. * A cool thing about most antibiotics: The target the bacteria and not our cells. * How does antibiotic resistance appear? * If the antibiotic targets a particular protein, a mutation may change the protein enough that it becomes more resistant. * It is fitter, and so it may multiply * If you don't take your full course of treatment, you are less likely to kill this mutant, and it survives to reproduce. * Vertical transfer: Natural selection * Change in environment -> kills population -> remainder are more fit -> breed -> the 'resistance' allelle is more likely to survive * Antibiotics create stress responses. One stress response is to be sloppy about making copies of DNA, which means that more mutations are likely. * Vertical transfer is bad enough, but things are worse * Remember acetinobacter experiments * That's right: Bacteria like to take up DNA. So if E. Coli has the mutant DNA, another bacterium can also pick up that DNA. Magic! We have another resistant bug. * A lot of the bacteria in your body are resistant to some antibioitic. * Horizontal transfer * Don't be grossed out about bacteria. Remember, 90% of YOU is bacteria. * That is, 90% of your cells is bacteria. * Making things worse * Farmers give all animals antibiotics, whether they need them or not * Doctors give people antibiotics, even if their disease is not bacterial in nature. * How can we identify whether horizontal transfer has happened? * Compare genomes. Things are really too similar at one gene. Why else would you care about comparing sequences? * Example from the book: Horizontal gene transfer * Explore evolution: Compare dinosaurs and chickens * Find out more about an unknown gene. If you're working in a different system, you might find out more about its behavior * The Praitis example * Found C. Elegans gene that affects development * Correlation in yeast * Also in human disease * Required whole-genome technology * Suggests experiments to do * Maybe give us deeper understanding of how sequences change, giving us the chance to create things that resist change * Not possible currently, but a hope for the future * Most antibiotics come from creatures, rather than from being create * Help identify where mutations happened. * Correlate multiple genetic changes * Some diseases have multiple genetic components * Engineering: If you have a protein that does something, you might look at all similar sequences *