1. Gènes sans frontières
in the evolving human
microbiome
Robert Beiko
Faculty of Computer Science
Dalhousie University
Thursday, April 17, 2014
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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
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.
11. Woese et al., PNAS (1990)
The dream of a Tree of Life
22. 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
27. 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
32. Growth on xyloglucans
Red: YES
Blue: NO
Green: MAYBE
Larsbrink et al. (2014) Nature
Dysgonomonas (termites!)
33. And…
Functional summary of Bacteroides thetaiotaomicron genes
http://meta.microbesonline.org
Poorly understood
VERY poorly understood
Not even *in* the analysis!
Metabolism?
Interactions?
34. 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?
35. Putting it all together:
The variable, evolving
microbiome
36. Smillie et al. (2011) Science
LGT by habitat type
~5% of all compared
genes?
38. Lachnospiraceae – Gut / mouth enthusiasts
(Conor) Meehan and Beiko (2014) GBE
“Good” strains ..?
“Not so good” strains ..?
Oral
Gut
Sediment (farm runoff)
Rumen
39. Butyrate production – a crucial
function, subject to LGT
Different candidate “species” trees -
All REJECTED!!
40. “Nickel / peptides transport system“ – poorly characterized!
Meehan and Beiko (2012) BMC Microbiol
41. 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.”
43. 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