Computational Biology II: Populations, evolution, interactions Antoine Frenoy 2020-11-09 2020-11-12 2020-11-24 2020-12-01 1 Computational biology? ● Developing computational tools to answer questions asked by biologists? – No! (or not only) ● Using computational tools and computational thinking to do research in biology (= asking & answering new biological questions) – The question determines the choice of tools, not the opposite – The thinking is often a bigger barrier than the tools – Deep Learning? Forget about it! 2 Who am I? ● First trained in computer science and cognitive sciences ● Then PhD and postdocs in microbiology and evolutionary biology – Bacterial genetics – Population dynamics – Computational models of evolution – Genomics and metagenomics 3 Your futur as a computational biologist? ● What are you interested in? – Software development, applied to biology or anything else? – Mathematical modeling, applied to biology or anything else? – Biology, using modeling and programming? ● It is never too late to change! ● What do you want to do next year and next decade? 4 And what if you are not particularly interested in computational biology? ● This course is an opportunity to discover the field and decide whether you want to go further ● It is normal and expected that the answer will be no for most of you – … in which case you will still take home some (hopefully) interesting and useful knowledge – … and should be able to get a passing grade with fairly moderate efforts ● For those who want to go further: – Advanced sections in the project – I will give pointers to extra readings 5 ● Do not hesitate to ask me for advice regarding PhD opportunities! Program of this class ● The first part of this class covered the “sequence – structure – function” paradigm ● This second part covers population dynamics, evolution and interactions ● Class partially based on independent readings ● Assessed with a small individual homework ● All informations available online: https://perso.crans.org/frenoy/compbiol/ 6 Where to find resources? ● Evolutionary Analysis, by Jon C Herron and Scott Freeman ● Evolutionary Dynamics, by Martin Nowak ● Read scientific articles on the topics you find interesting ● Implement new knowledge as a computational model! ● Download scientific articles: sci-hub ● Download textbooks: libgen and r/textbookrequest 7 Biology, the science of the 21st century? Source: WHO “Malaria may have killed half of all the people that ever lived”, John Whitfield 8 Is the infectious diseases problem solved? ● “When I got my PhD in 1951, my supervisor said: 'Malaria's dead - you'll never make a living from it'”, Robert Desowitz ● But... McClure & Day, 2014 9 Why do these drugs stop working? What has changed: the drug, the host, or the pathogen? Herron & Freeman, adapted from Larder et al 1989 → The pathogen evolved towards drug resistance 10 Mutations are random: Luria & Delbruck 1943 11 Mutations are random: Lamarckism and Darwinism 12 Antibiotic Evolution+ selection =(random)mutations For example, evolution of antibiotic resistance in bacteria Resistance Mutations Selection 13 Evolution by positive selection driving genetic change over time From Herron & Freeman 14 Genetic Drift Population size N=40 Herron & Freeman Population size N=400 Following a neutral allele from initial frequency 0.5 (several realisations for two population sizes) Genetic drift = changes due to random sampling → higher stochasticity in smaller populations 15 A bit of computational thinking about drift 16 Combined action of drift and positive selection Same effect of drift when combined with selection: higher stochasticity in smaller populations adapted from Rich et al 1979 by Herron & Freeman 17 Evolution by purifying selection: selection preventing deleterious genetic changes Reminder: positive selection 18 Experimental evolution in the lab Barrick & Lenski, 2013 19 Conclusion of 1st lecture, homework ● Have a detailed look on the project, prepare your questions for next lecture ● (Before 2020-11-17) read this text from Laurent Duret on neutral evolution and the controversy around it ● (Optional) read this review from Barrick & Lenski on experimental evolution ● Questions? 20.