Origin and Evolution of the Microbiome

Margaret McFall-Ngai,Dept of Medical Microbiology and Immunology

Symbiosis ClusterUniversity of Wisconsin Madison

Interplay of Microbiome, Environmental Stressors, and Human HealthWashington, DC, April 2011

Origin and Evolution of the Microbiome

Outline

1. Humans as components of the animal kingdom -Who are we and how did we get here?

2. Evolution of the epithelium-immune-microbiota interaction

epithelium mucosal immunesystem

bacterial consortium Microbiota

MacPherson & Harris (2004) Nat Rev Immunol

Cretaceous

Jurassic

Triassic

Quaternary

Tertiary

MES

OZO

ICP

ALE

OZO

IC

Permian

Carboniferous

Devonian

Silurian

Ordovician

Cambrian earliest vertebrates

earliest jawed vertebratesLophotrochozoa

Ecdysozoa

earliest tetrapods

earliest mammals

Homo sapiens

225

65

550

Millions of years ago

ALL animal body plans diverged

Deuterostomia

CEN

OZO

IC

Bilateria

Deuterostomia

Protostomia

Metazoa

Porifera, Cnidaria, Ctenophora(sponges, corals, comb jellies)

Chordata (tunicates, lancelet, fish, human)

Hemichordata (acorn worms)

Echinoderms (sea urchin)

Lophotrochozoa

Ecdysozoa

Molluscs and others

Annelidsand others

Nematodesand others

Arthropodsand others

the vertebrates

Unicellular organisms

Over 96% of animal diversity

non-vertebrate

On their own complex

evolutionary paths

Bilateria

Deuterostomia

Protostomia

Metazoa





Lophotrochozoa

Ecdysozoa

Molluscs and others

Annelidsand others

Nematodesand others


the vertebrates


(Domazet-Loso and Tautz, 2008)

The evolutionary trajectory to humans in 19 steps -

Question: At which steps in evolution did the human genes evolve?

Method: All available proteins sequences were used to create a phylographic framework, within which the positions of human protein sequences (~23, 000) were identified.

Gen

e N

umbe

r10,000

1,000

10

11 2 3 4 5

100

Genome

Disease

6 7 8 9 10 11 12 13 14 15 16 17 18 19

Phylostrata

Animals

Mammals

Primates

Jawed Vertebrates

Origin of Human Genes/Genes Associated with Human Genetic Disease

(Domazet-Loso and Tautz, 2008) Phylostrata

(1,760/22,937)

Gen

e N

umbe

r10,000

1,000

10

11 2 3 4 5

100

Genome

Disease

6 7 8 9 10 11 12 13 14 15 16 17 18 19

Phylostrata

Animals

Mammals

Primates

Jawed Vertebrates


(Domazet-Loso and Tautz, 2008) Phylostrata

(1,760/22,937)

Genes involved in genetic disease are biased toward ancient genes.

Thus, for an understanding of the human microbiome:

Can we derive basic principles of animal-bacterial interactions from an understanding of the patterns of evolution of genes?

Gen

e N

umbe

r10,000

1,000

10

11 2 3 4 5

100

Genome

Disease

15 16 17 18 19

Mammals Jawed Vertebrates


Principally immune-related

Overrepresented in immune-related

Animals

Principally signaling

Overrepresented incell-cell

communication

(Domazet-Loso and Tautz, 2008)

6 7 8 9 10 11 12 13 14

Phylostrata

Bioinformatic approaches to evolution of animals Models of animal-bacterial associations - an evolutionary tool kit

Insights into human biology

“Given that over 90% of the disease genes have emerged before the bilaterian radiation, it seems justified to use the organisms that are evolutionarily very remote

as models for studying the function of disease genes”[Domazet-Loso and Tautz, 2008]

Bilateria

Deuterostomia

Protostomia

Metazoa





Lophotrochozoa

Ecdysozoa

Molluscs and others

Annelidsand others

Nematodesand others


the vertebrates


Environmental context for the evolution of animal body plans - what drove selection on the mucosa?

Environment of the oceans

> 99% of all the organic matter in dissolved (DOM) rather than particulate form[Hedges (1987) Nature 330:205)]

~ 105-106 bacteria/ml of seawater

Environment of the oceans

> 99% of all the organic matter in dissolved (DOM) rather than particulate form[Hedges (1987) Nature 330:205)]

~ 105-106 bacteria/ml of seawater

Evolution of animal body plans

-- selection for the uptake of DOM across the body wall in most, if not all, soft-bodied marine invertebrates

Challenge of opposite ‘goals’-- taking up DOM and preventingovergrowth of their tissues by the microorganisms thatshare the nutrient pool

Milestones in animal evolution

multicellularity

tissue layers (diploblastic - endoderm/ectoderm)

bilateral (triploblastic - +mesoderm)

complete gut

coelom

sponges

anemones

flatwormsribbonworms

insects vertebrates

mollusks

Milestones in animal evolution

multicellularity

tissue layers (diploblastic - endoderm/ectoderm)

bilateral (triploblastic - +mesoderm)

complete gut

coelom

sponges

anemones

flatwormsribbonworms

insects vertebrates

mollusks

EPITHELIA

INTERNAL TISSUELAYERS, ORGANS

one-way digestion,GUT REGIONALIZATION

GUT SEPARATED FROMBODY WALL

Thomas Bosch Christian-Albrechts University Kiel, Germany

Hydra spp.

Many responses of animals to the microbial world are ancient and conserved.

Hydra frozen section EM, TCG Bosch

www.visualsunlimited.com/requestform.jsp

Human small intestine

Hydra body column

Hydra – a new model in innate immunityHydra has two cell layers - epidermis (derived from ectoderm) and gastrodermis (derived from endoderm)

http://www.visualsunlimited.com/requestform.jsp

Fraune & Bosch (2010) BioEssays

Fraune & Bosch (2007) Proc.Natl.Acad.Sci USA

Fraune & Bosch (2009) Microbe

Fraune et al (2010) Proc.Natl.Acad.Sci USA

Analysis of bacteria associated with different Hydra species

Fraune & Bosch (2010) BioEssays

Fraune & Bosch (2007) Proc.Natl.Acad.Sci USA

Fraune & Bosch (2009) Microbe

Fraune et al (2010) Proc.Natl.Acad.Sci USA

Analysis of bacteria associated with different Hydra species

Environmental isolates & long-term lab cultures

Role of TLR-pathway in host-microbe interactions

Transgenic knock-down of MyD88

TLR signalling is required for host –microbe interaction

…From Hydra to man: TLR-2 knockout mutants have altered microbiota.

Cretaceous

Jurassic

Triassic

Quaternary

Tertiary

MES

OZO

ICP

ALE

OZO

IC

Permian

Carboniferous

Devonian

Silurian

Ordovician

Cambrian earliest vertebrates

earliest jawed vertebratesLophotrochozoa

Ecdysozoa

earliest tetrapods

earliest mammals

Homo sapiens

225

65

550

Millions of years ago


Deuterostomia

CEN

OZO

IC

Water-to-LandTransition

first evidence

Radiation of members of 7 of the ~36 animal phyla,

(representatives in all three subkingdoms)

Most vertebrates are aquatic.

Agnatha (80)

Chondrichthys (900)

Actinopterygii (25,000) Fishes

Actinistia + Dipnoi (8) Urodeles (415)

Anura (4300)

Amph

ibia

ns

Reptile

s

Birds

Mammalia (4500)

Aves(9100)

Gymnophiona (165)

Testudinia (260)

Lepidosauria(6800)

Crocodilia (22)

Mam

mals

Water-to-Land Transition

Land animals [and plants] require mechanisms:

of structural supportto respireto reproduceto avoid desiccation

Water-to-Land Transition

Land animals [and plants] require mechanisms:

of structural supportto respireto reproduceto avoid desiccation

require substantial remodeling of the mucosa

The integration of microbiologyand host biology

= a revolution in biology

Our concept of the nature of the immune system

Cretaceous

Jurassic

Triassic

Quaternary

Tertiary

ME

SO

ZOIC

PA

LEO

ZOIC

Permian

Carboniferous

Devonian

Silurian

Ordovician

Cambrian

earliest vertebrates

earliest jawed vertebrates

Lophotrochozoa

Ecdysozoa

earliest tetrapods

earliest mammals

Homo sapiens

225

65

550

mya


Deuterostomia

CE

NO

ZOIC

adaptive immune system

Porifera(sponges)

EchinodermataChordata

Cephalochordata

Urochordata

Vertebrata

Agnatha

Cartilagenousfishes (sharks, rays)

Bony fishes

Amphibians

Reptiles

Birds

Mammals

The mechanism enabling somatic recombination appears at the agnathan - gnathostome transition.

Lophotrochozoa

Ecdysozoa

Deuterostomia

Vertebrates - 4%

Agnathan(jawless)

Gnathostome(jawed)

Invertebrates - 96%

Invertebrates Vertebrates

Binary associationsintra- or extracellular common rare

Stable, coevolved, consortial symbioses rare common

Basic differences in immunity between invertebrates and vertebrates may reflect the way they interact with microbes:

Correlated immunity: innate only innate + adaptive

Invertebrates Vertebrates

Binary associationsintra- or extracellular common rare

Stable, coevolved, consortial symbioses rare common

Basic differences in immunity between invertebrates and vertebrates may reflect the way they interact with microbes:

Correlated immunity: innate only innate + adaptive

Could a principal selection pressure on the evolution of the vertebrate adaptive immune system be the requirement of the host to maintaincoevolved communities in balance?

INVERTEBRATES VERTEBRATES

Association withmicroorganisms

Immune system:selection on, and function of

restrictive permissive

non-self control of a set recognition of communities

Both bioinformatic approaches and functional studies provide evidence that animal-bacterial interactions

involve ancient, conserved characters.

Our new knowledge of the patterns and prevalence of these interactions demands that we question some of our

basic premises (e.g., the form and function of the immune system).

Conclusions

Thank you!

Questions?

Origin and Evolution of the Microbiome

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