1. The human microbiome is complex and diverse, consisting of many bacterial taxa that play important roles in human health and disease. 2. Lateral gene transfer is an important process that allows for innovation and functional changes in the microbiome over time and in response to environmental conditions. 3. While taxonomic diversity does not always predict functional diversity, analysis of microbial genomes and gene functions is helping researchers better understand the metabolic capabilities and ecological roles of microbiome communities.

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?
…

11. Woese et al., PNAS (1990)
The dream of a Tree of Life

12. Holy
moley!
Rinke et al., Nature (2013)
E
T
A
P

13. A
T
E
P
Wu and Eisen, Genome Biol (2008)
But wait!

14. Wu … Eisen, Nature (2009)
T
A
E
P
But continue
to wait!

16. (Rob) Eveleigh et al. (2013)
Genme Biol Evol
A
E
T
P

17. 244 taxa
40,631 trees
= Bacterial SPR supertree
LGT patterns for Clostridium
(Chris) Whidden et al. (2014) Syst Biol

18. How important is LGT?
Not at all
Useful in
some cases
A central mode of
microbial innovation

19. Microbial ecology stories
who is there
what are they doing
how will they respond
Frederic
Clements
Henry
Gleason
Communities? Assemblages?

20. Human host
Microbes Environment
And if the bugs in you start playing a different tune…

21. TAXONOMY
Lacnhnospiraceae
Lactobacillaceae
You get the idea
Fecal microbiome samples from young,
middle-aged and old mice
(Morgan) Langille et al., in preparation

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

23. Dissimilarity matrices
and ordination
S1 S2
S2 0.8 ---
S3 0.7 0.3
Langille et al., in preparation

24. Jessie Ning
Data from the Human Microbiome Project

25. What is the key assumption
of phylogenetic -diversity
measures?

26. FUNCTION
Baumann et al. (2007) Plant Cell
Larsbrink et al. (2014) Nature

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

28. It works
surprisingly
well!
Langille et al. (2013) Nat Biotechnol

29. The microbiome:
Functional similarities,
taxonomic differences
Huttenhower et al. (2012) Nature

30. So, function is conserved in
spite of major differences in
taxonomy

31. Huh?
Huttenhower et al. (2012) Nature
!!!!
!!!!

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?

37. Hehemann et al. (2010) Nature

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.”

42. 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

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