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2014 04-beiko-biology

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April 2014 seminar presented to Department of Biology, Dalhousie University

April 2014 seminar presented to Department of Biology, Dalhousie University

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  • 1. Gènes sans frontières in the evolving human microbiome Robert Beiko Faculty of Computer Science Dalhousie University Thursday, April 17, 2014 è SlideShare: http://www.slideshare.net/beiko/2014-04beikobiology beiko@cs.dal.ca / @rob_beiko FRAGILIS BACTEROIDES 14 APRIL 2014 A DISTAL COLON POO8675309 15 APR 2014 17 APR 2014Source Molecular Corporation
  • 2. The micro- what? www.futuretimeline.net Lateral gene transfer The Breakfast Organisms "Bacon Fields" Author: Michael DeForge Microbial ecology and biogeography More hypotheses!The story so far Hypotheses! www.discovercreation.org
  • 3. “Micro-biome” “Microbi-ome” As assessed through sequencing and other techniques 3
  • 4. Why does the microbiome matter?
  • 5. 5 Qin et al., Nature (2010) The human microbiome is complex
  • 6. The human microbiome can reflect healthy or diseased states 6
  • 7. The human microbiome is essential during development 7Koenig et al., PNAS 2011
  • 8. “My First Microbiome” Yatsunenko et al., Nature 2012 8
  • 9. The human microbiome offers new routes of intervention van Nood et al. (2013) NEJM Administered via nasojejunal tube Irritable bowel syndrome? Inflammatory bowel disease? (e.g., Crohn’s) Neurological conditions? …
  • 10. Woese et al., PNAS (1990) The dream of a Tree of Life
  • 11. Holy moley! Rinke et al., Nature (2013) E T A P
  • 12. A T E P Wu and Eisen, Genome Biol (2008) But wait!
  • 13. Wu … Eisen, Nature (2009) T A E P But continue to wait!
  • 14. (Rob) Eveleigh et al. (2013) Genme Biol Evol A E T P
  • 15. 244 taxa 40,631 trees = Bacterial SPR supertree LGT patterns for Clostridium (Chris) Whidden et al. (2014) Syst Biol
  • 16. How important is LGT? Not at all Useful in some cases A central mode of microbial innovation
  • 17. Microbial ecology stories who is there what are they doing how will they respond Frederic Clements Henry Gleason Communities? Assemblages?
  • 18. Human host Microbes Environment And if the bugs in you start playing a different tune…
  • 19. TAXONOMY Lacnhnospiraceae Lactobacillaceae You get the idea Fecal microbiome samples from young, middle-aged and old mice (Morgan) Langille et al., in preparation
  • 20. Qualitative β-diversity = presence / absence of different groups Quantitative β-diversity = relative abundance of different groups Phylogenetic β-diversity = either of the above, but related groups contribute less to diversity Comparing samples Outcome: 0 = identical 1 = maximally different
  • 21. Dissimilarity matrices and ordination S1 S2 S2 0.8 --- S3 0.7 0.3 Langille et al., in preparation
  • 22. Jessie Ning Data from the Human Microbiome Project
  • 23. What is the key assumption of phylogenetic -diversity measures?
  • 24. FUNCTION Baumann et al. (2007) Plant Cell Larsbrink et al. (2014) Nature
  • 25. Can we predict function, based on taxonomy? PICRUSt Langille et al. (2013) Nat Biotechnol Sequenced genomes (known function) Reference phylogeny (known function + unknown function) = FUNCTIONAL PREDICTIONS
  • 26. It works surprisingly well! Langille et al. (2013) Nat Biotechnol
  • 27. The microbiome: Functional similarities, taxonomic differences Huttenhower et al. (2012) Nature
  • 28. So, function is conserved in spite of major differences in taxonomy
  • 29. Huh? Huttenhower et al. (2012) Nature !!!! !!!!
  • 30. Growth on xyloglucans Red: YES Blue: NO Green: MAYBE Larsbrink et al. (2014) Nature Dysgonomonas (termites!)
  • 31. And… Functional summary of Bacteroides thetaiotaomicron genes http://meta.microbesonline.org Poorly understood VERY poorly understood Not even *in* the analysis! Metabolism? Interactions?
  • 32. Key messages? 1. Taxonomic diversity can be useful 2. And is somewhat predictive of function 3. Even though the basic assumption is often violated 4. To really get a handle on function, you need to drill down, both taxonomically and functionally 5. And what about hypotheticals?
  • 33. Putting it all together: The variable, evolving microbiome
  • 34. Smillie et al. (2011) Science LGT by habitat type ~5% of all compared genes?
  • 35. Hehemann et al. (2010) Nature
  • 36. Lachnospiraceae – Gut / mouth enthusiasts (Conor) Meehan and Beiko (2014) GBE “Good” strains ..? “Not so good” strains ..? Oral Gut Sediment (farm runoff) Rumen
  • 37. Butyrate production – a crucial function, subject to LGT Different candidate “species” trees - All REJECTED!!
  • 38. “Nickel / peptides transport system“ – poorly characterized! Meehan and Beiko (2012) BMC Microbiol
  • 39. More LGT and the microbiome “…not only the bacterial taxa, but also their plasmids, are defined by the ecological niche.” PNAS,2013 PNAS,2012 “…pathogen-driven inflammatory responses in the gut can generate transient enterobacterial blooms in which conjugative transfer occurs at unprecedented rates.” PLoSBiol,2007 “…lateral gene transfer, mobile elements, and gene amplification have played important roles in affecting the ability of gut-dwelling Bacteroidetes to vary their cell surface, sense their environment, and harvest nutrient resources present in the distal intestine.”
  • 40. What does it all mean? © Lucasfilm en.wikipedia.org Brooding Commensal Evil Pathogen Lord Redeemed Mutualist Enabled by LGT, gene loss, and mutation The Role Transformation Hypothesis
  • 41. Acknowledgments Beiko lab • Morgan Langille • Conor Meehan • Jeremy Koenig • Jessie Ning • Chris Whidden • Rob Eveleigh • Dennis Wong Mouse Frailty • Susan Howlett • Rob Rose LGT Algorithms / Communities • Norbert Zeh • John Archibald • Eva Boon PICRUSt • Jesse Zaneveld • Rob Knight • Curtis Huttenhower • Greg Caporaso • Dan Knights • Daniel MacDonald • Josh Reyes • Jose Clemente