1. Nothing in Microbiology makes Sense except in the Light of Evolution Professor Mark Pallen

2. Online extras Live tweet #palleninaugural Slides available at http://www.slideshare.net/mpallen/pallen- inaugural-warwickfinal Online guide https://blogs.warwick.ac.uk/microbialun derground https://storify.com/mjpallen/palleninaug ural YouTube https://www.youtube.com/user/Warwick MedicalSchool https://www.youtube.com/user/pallenm Unofficial after- lecture drinks at The Varsity pub, CV4 7AJ 3. In Memoriam Fred Sanger 13 Aug 1918 19 Nov 2013 Carl Woese Jul 15, 1928 Dec 30, 2012 Steve Jobs Feb 24, 1955 Oct 5, 2011 Si monumentum requiris, circumspice 4. Acknowledgements We were united by a common love of Science, which we thought sufficient to bring together persons of all distinctions, Christians, Jews, Muslims and Heathens, Monarchists and Republicans. Joseph Priestley on the Birmingham Lunar Society, 1793 5. Acknowledgements We were united by a common love of Science, which we thought sufficient to bring together persons of all distinctions, Christians, Jews, Muslims and Heathens, Monarchists and Republicans. Joseph Priestley on the Birmingham Lunar Society, 1793 6. I am not obsessed with Darwin ...despite quoting him at my wedding, calling my first two children Emma and Charles, being on first name terms with two of his descendants, writing scholarly works about his views on religion! John van Wyhe, Alison Pearn, Randal Keynes are all obsessed with Darwin I just have a passing interest But I dont want to let my audience down 7. What is to be covered History of life History of science History of me and my science Century by century, Decade by decade 8. The Origin: November 24th 1859 1859-1959 1960s 1970s 1980s 1990s 2000s 2010s 9. From 1859 to 1959 Darwin's Influence on Modern Thought notion of branching evolution common descent of all living things from a single origin the mechanism of evolution is (largely) natural selection evolution gradual no major discontinuities evolutionary biology, by contrast with physics and chemistry, is a historical science evolutionist attempts to explain events/processes that have already taken place feeds on variation and randomness banishing typology and determinism Ernst Mayr Jul 5, 1904 Feb 3, 2005 10. Tools to think with Darwins Notebooks If we choose to let conjecture run wild, then animals our fellow brethren in pain, disease, death and suffering, and famine, our slaves in the most laborious works, our companions in our amusements; they may partake from our origin in one common ancestor; we may be all netted together 11. From 1859 to 1959: Genetics 1860s Mendels experiments on peas 1900s onwards Rediscovery of Mendel (de Vries, Correns, Bateson) Soma/germ-line distinction (Weismann) Chromosomes; mutations (Morgan) 1940s Modern Synthesis of Evolution and Genetics (Fisher, Haldane, Wright, Dodzhansky, Mayr) 12. From 1830s to 1959: Computing 1837 Analytical Engine: Babbage 1842 Ada Lovelace: first program 1854 Boolean algebra 1936 Turing machines 1950s First transisterized computers 13. From 1859 to 1959: Germ Theory 1860s Pasteur demolishes spontaneous generation 1870s Koch links anthrax to bacteria Cohn founds bacterial taxonomy Cohn and Darwin correspond 1880s TB; cholera; diphtheria; antiserum 14. From 1859 to 1959 1942: Bacteria dont have genetics [bacteria] have no genes in the sense of accurately quantized portions of hereditary substance; and therefore they have no need for the accurate division of the genetic system which is accomplished by mitosis Julian Huxley, 1942 15. From 1859 to 1959 1951: Bacteria do have genetics Chapter onMutation and selection in microorganisms in Dobzhanskys 1951 Genetics and the Origin of Species Demerec (1945) and Luria (1946) showed that penicillin-resistant strains of Staphylococcus aureus arise by mutations which survive in the presence of enough penicillin in the medium to kill most individuals of the parental strain. 16. From 1859 to 1959 1953: from Darwin to DNA Darwin, Nature April 1882 through the kindness of Mr W. D. Crick of Northampton Crick and Watson, Nature, April 1953 beetle bivalve 17. 1960: I am born! 18. 1964: Dobzhanskys dictum 19. Sidestep: Sequences Genes: DNA Proteins Information Storage Genes consist of sequences of characters from 4-base alphabet ACTG Information into Action Proteins consist of sequences of characters from 20-amino-acid alphabet encode All the genes, all the DNA in a bacterium = its Genome Sequence its complete genetic blueprint 20. 1965: Zuckerkandl and Pauling sequence homology and molecular phylogenetics 21. Sidestep: Sequence homology Languages and informational macromolecules consist of sequences of characters that show descent with modification Similarity due to descent from common ancestor (homology) can be used to infer function or meaning one, two, three eins, zwei, drei un, deux, troi Hittite (20-13th C BCE) nu NINDA-n ezzateniwatar-ma ekutteni Now you will eat BREAD, And you will drink water Hrozn, Bedich (1917) nu BREAD-n ezzateniwatar-ma ekutteni 22. 1970s: Sanger invents DNA sequencing 23. 1970s: me Wallington High School Must learn to control his grasshopper mind! The primary purpose of a liberal education is to make one's mind a pleasant place in which to spend one's time Sydney J. Harris DNA is not in the textbooks! But Cambridge entrance exam asks for protein sequence assembly! 24. 1980s: me Fitzwilliam College, Cambridge How much genome is there in a pork pie? Final year project on Leprosy London Hospital Royal Free Barts I know that I ought to feel ashamed of days and evenings thus spent, but as some of my friends were very pleasant and we were all in the highest spirits, I cannot help looking back to these times with much pleasure. During the three years which I spent at Cambridge my time was wasted, as far as the academical studies were concerned 25. 1987: Bacteria join Darwins tree of life Eucarya Archaea Bacteria 26. As the 1980s turned into the 1990s Exploiting computers to find sequence homology Helicobacter pylori A bacterial urease shows homology to a plant urease! Clostridium difficile Butanol fermentation genes (same pathway that earned Chaim Weizmann the Balfour Declaration) Reverse transcriptase and a group II intron 27. From 1990s: Proteins and domains The search for distant homologies Signal Peptide A B Coiled coil domain C D Transitivity of Homology Proteins consist of domains Distant Homology Signal Peptide Let two forms have not a single character in common, yet if these extreme forms are connected together by a chain of intermediate groups, we may at once infer their community of descent, and we put them all into the same class. Origin of Species CHAPTER 14 28. From 1990s: Stress! The lab-cultured bacterium is an artifact Life...in a state of nature is solitary, poor, nasty, brutish and short Thomas Hobbes In the wild, bacteria face stressful feast fast or famine lifestyle During infection, host responses cause stress WT-funded PhD on starvation stress in Salmonella BBSRC grant to use microarrays in follow-up study 29. From 1990s: Stress! Emma Nov 5th 1995 Charlie Mar10th 1997 Natasha Aug 3rd 1999 Tom Jan 7th 2002 Final Late October 1995 30. From 1990s: Bacterial Pathogenomics Discovered Biology Undiscovered Biology 31. From 1990s: Bacterial Pathogenomics 32. From 1990s: Tools to think with Internet Databases 33. 1999-2001 From Barts to Belfast to Birmingham 34. 2000s E. coli: avoiding typological thinking And God created E. coli K-12 MG1655? 35. 2000s: Evolution in E. coli Genome Degeneration and convergent evolution 36. 2000s: Evolution in E. coli Virulence Effectors 37. 2000s: Evolution in E. coli and beyond The Evolution of Complexity 38. 2000s: Darwin Days Evolution as obsession and reward 39. 2008: Genomes as documents of evolutionary history 40. Sequencing singularity From 2008: High-throughput sequencing brings genomes for the masses 41. 2010s: Bacterial evolution within outbreaks 42. 2011-2012 Acinetobacter Outbreak First reported case July 2011 (military patient) Outbreak lasted 80 weeks and involved 60 patients, including military and civilian patients >90 isolates from patients and environment genome-sequenced on Illumina MiSeq, including multiples from same patient (different time and body sites) Reconstructed phylogenetic tree and potential transmission chains, focussing infection control efforts on an operating theatre 43. 2010s: Darwin in the drug store Genomes of two Acinetobacter baumannii isolates from single patient sequenced before tigecycline therapy (susceptible) and after therapy (resistant) Eighteen changes detected between AB210 and AB211 nine non-synonymous, including mutation in adeS which accounts for resistance Three sections of early genome missing in late genome, loss of DNA repair gene, causing increase in mutation rate? Planned work on MDR TB Madikay Senghore, Martin Antonio 44. 2011: Social Evolution Open-Source Genomics 45. 2013 onwards: genome to metagenome Challenging Gram and Koch 46. 2013 onwards: ancient DNA Genomes as documents of human history 47. 2013 onwards: Negativicutes when Gram stain and genealogy conflict 48. 2014 onwards : Tools to think with CLIMB consortium 49. 2014 onwards: Tools to think with Enterobase "More individuals are born than can possibly survive. A grain in the balance will determine which individual shall live and which shall diewhich variety or species shall increase in number, and which shall decrease, or finally become extinct... The slightest advantage in one being, at any age or during any season, over those with which it comes into competition, or better adaptation in however slight a degree to the surrounding physical conditions, will turn the balance. Origin of Species, 1859, Charles Darwin "More proposals are submitted than can possibly be funded. A grain in the balance will determine which proposal shall be funded and which shall die which research group or institution shall increase in number, and which shall decrease, or finally become extinct The slightest advantage in one proposal, at any stage or during any meeting, over those with which it comes into competition, or better adaptation in however slight a degree to the surrounding political conditions, will turn the balance. Origin of Research Projects, 2014 50. There is grandeur in this view of life, with its several powers having been originally breathed into a few forms or into one; and that whilst this planet has been cycling on according to the fixed law of gravity, from so simple a beginning endless forms most beautiful and most wonderful have been, and are being, evolved. Back to 1859: Darwins grandeur