2014 04-beiko-biology
DESCRIPTION
April 2014 seminar presented to Department of Biology, Dalhousie UniversityTRANSCRIPT
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Gènes sans frontièresin 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/[email protected] / @rob_beiko
FRAGILIS
BACTEROIDES
14 APRIL 2014
A DISTAL COLON
POO8675309
15 APR 2014
17 APR 2014Source Molecular Corporation
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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
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“Micro-biome”
“Microbi-ome”
As assessed through sequencing
and other techniques
3
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Why does the microbiome matter?
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5Qin et al., Nature (2010)
The human microbiome is complex
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The human microbiome can reflect healthy or diseased states
6
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The human microbiome is essential during development
7Koenig et al., PNAS 2011
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“My First Microbiome”
Yatsunenko et al., Nature 2012 8
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The human microbiome offersnew 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?…
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Woese et al., PNAS (1990)
The dream of a Tree of Life
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Holy moley!
Rinke et al., Nature (2013)
E
T
A
P
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A
T
EP
Wu and Eisen, Genome Biol (2008)
But wait!
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Wu … Eisen, Nature (2009)
T
AE
P
But continueto wait!
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(Rob) Eveleigh et al. (2013) Genme Biol Evol
A
E
TP
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244 taxa40,631 trees= Bacterial SPR supertree
LGT patterns for Clostridium
(Chris) Whidden et al. (2014) Syst Biol
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How important is LGT?
Not at all
Useful in some cases
A central mode of microbial innovation
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Microbial ecology storieswho is therewhat are they doinghow will they respond
FredericClements
Henry Gleason
Communities? Assemblages?
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Human host
Microbes Environment
And if the bugs in you start playing a different tune…
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TAXONOMY
Lacnhnospiraceae
Lactobacillaceae
You get the idea
Fecal microbiome samples from young, middle-aged and old mice(Morgan) Langille et al., in preparation
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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 = identical1 = maximally different
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Dissimilarity matrices
and ordination
S1 S2
S2 0.8 ---
S3 0.7 0.3
Langille et al., in preparation
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Jessie NingData from the Human Microbiome Project
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What is the key assumptionof phylogenetic -diversity
measures?
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FUNCTION
Baumann et al. (2007) Plant Cell
Larsbrink et al. (2014) Nature
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Can we predict function, based on taxonomy?
PICRUSt
Langille et al. (2013) Nat Biotechnol
Sequenced genomes(known function)
Reference phylogeny(known function +unknown function)
= FUNCTIONALPREDICTIONS
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It workssurprisingly well!
Langille et al. (2013) Nat Biotechnol
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The microbiome:Functional similarities,taxonomic differences
Huttenhower et al. (2012) Nature
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So, function is conserved in spite of major differences in
taxonomy
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Huh?
Huttenhower et al. (2012) Nature
!!!!
!!!!
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Growth on xyloglucans
Red: YES
Blue: NO
Green: MAYBE
Larsbrink et al. (2014) NatureDysgonomonas (termites!)
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And…
Functional summary of Bacteroides thetaiotaomicron geneshttp://meta.microbesonline.org
Poorly understood
VERY poorly understood
Not even *in* the analysis!
Metabolism?
Interactions?
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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?
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Putting it all together:The variable, evolving
microbiome
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Smillie et al. (2011) Science
LGT by habitat type
~5% of all compared
genes?
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Hehemann et al. (2010) Nature
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Lachnospiraceae – Gut / mouth enthusiasts
(Conor) Meehan and Beiko (2014) GBE
“Good” strains ..?
“Not so good” strains ..?
Oral
Gut
Sediment (farm runoff)
Rumen
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Butyrate production – a crucial
function, subject to LGT
Different candidate “species” trees -All REJECTED!!
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“Nickel / peptides transport system“ – poorly characterized!
Meehan and Beiko (2012) BMC Microbiol
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More LGT and the microbiome
“…not only the bacterial taxa, but also their plasmids, are defined by the ecological niche.”
PN
AS, 2
01
3
PN
AS, 2
01
2
“…pathogen-driven inflammatory responses in the gut can generate transient enterobacterialblooms in which conjugative transfer occurs at unprecedented rates.”
PLo
SB
iol, 2
00
7
“…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.”
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What does it all mean?
© Lucasfilmen.wikipedia.org
Brooding Commensal Evil Pathogen Lord Redeemed Mutualist
Enabled by LGT, gene loss, and mutation
The Role Transformation Hypothesis
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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
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