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/2014-04beikobiologybeiko@cs.dal.ca / @rob_beiko

FRAGILIS

BACTEROIDES

14 APRIL 2014

A DISTAL COLON

POO8675309

15 APR 2014

17 APR 2014Source Molecular Corporation

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

“Micro-biome”

“Microbi-ome”

As assessed through sequencing

and other techniques

3

Why does the microbiome matter?

5Qin et al., Nature (2010)

The human microbiome is complex

The human microbiome can reflect healthy or diseased states

6

The human microbiome is essential during development

7Koenig et al., PNAS 2011

“My First Microbiome”

Yatsunenko et al., Nature 2012 8

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?…

Woese et al., PNAS (1990)

The dream of a Tree of Life

Holy moley!

Rinke et al., Nature (2013)

E

T

A

P

A

T

EP

Wu and Eisen, Genome Biol (2008)

But wait!

Wu … Eisen, Nature (2009)

T

AE

P

But continueto wait!

(Rob) Eveleigh et al. (2013) Genme Biol Evol

A

E

TP

244 taxa40,631 trees= Bacterial SPR supertree

LGT patterns for Clostridium

(Chris) Whidden et al. (2014) Syst Biol

How important is LGT?

Not at all

Useful in some cases

A central mode of microbial innovation

Microbial ecology storieswho is therewhat are they doinghow will they respond

FredericClements

Henry Gleason

Communities? Assemblages?

Human host

Microbes Environment

And if the bugs in you start playing a different tune…

TAXONOMY

Lacnhnospiraceae

Lactobacillaceae

You get the idea

Fecal microbiome samples from young, middle-aged and old mice(Morgan) Langille et al., in preparation

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

Dissimilarity matrices

and ordination

S1 S2

S2 0.8 ---

S3 0.7 0.3

Langille et al., in preparation

Jessie NingData from the Human Microbiome Project

What is the key assumptionof phylogenetic -diversity

measures?

FUNCTION

Baumann et al. (2007) Plant Cell

Larsbrink et al. (2014) Nature

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

It workssurprisingly well!

Langille et al. (2013) Nat Biotechnol

The microbiome:Functional similarities,taxonomic differences

Huttenhower et al. (2012) Nature

So, function is conserved in spite of major differences in

taxonomy

Huh?

Huttenhower et al. (2012) Nature

!!!!

!!!!

Growth on xyloglucans

Red: YES

Blue: NO

Green: MAYBE

Larsbrink et al. (2014) NatureDysgonomonas (termites!)

And…

Functional summary of Bacteroides thetaiotaomicron geneshttp://meta.microbesonline.org

Poorly understood

VERY poorly understood

Not even *in* the analysis!

Metabolism?

Interactions?

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?

Putting it all together:The variable, evolving

microbiome

Smillie et al. (2011) Science

LGT by habitat type

~5% of all compared

genes?

Hehemann et al. (2010) Nature

Lachnospiraceae – Gut / mouth enthusiasts

(Conor) Meehan and Beiko (2014) GBE

“Good” strains ..?

“Not so good” strains ..?

Oral

Gut

Sediment (farm runoff)

Rumen

Butyrate production – a crucial

function, subject to LGT

Different candidate “species” trees -All REJECTED!!

“Nickel / peptides transport system“ – poorly characterized!

Meehan and Beiko (2012) BMC Microbiol

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.”

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

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