Download McFall-Ngai microbiome - NAS

Interplay of Microbiome, Environmental Stressors, and Human Health
Washington, DC, April 2011
Origin and Evolution of the Microbiome
Margaret McFall-Ngai,
Dept of Medical Microbiology and Immunology
Symbiosis Cluster
University of Wisconsin Madison
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
mucosal immune
system
epithelium
bacterial consortium
Microbiota
MacPherson & Harris (2004) Nat Rev Immunol
CENOZOIC
Quaternary
Millions of
years ago
MESOZOIC
Tertiary
Homo sapiens
65
Cretaceous
Jurassic
Triassic
earliest mammals
225
Permian
Carboniferous
earliest tetrapods
PALEOZOIC
Devonian
Deuterostomia
Silurian
Ecdysozoa
Ordovician
Cambrian
Lophotrochozoa
earliest jawed vertebrates
earliest vertebrates
550
ALL animal body
plans diverged
Lophotrochozoa
Molluscs
and others
Protostomia
Annelids
and others
Over 96%
of animal diversity
non-vertebrate
Nematodes
Bilateria
and others
Arthropods
Ecdysozoa
Metazoa
Deuterostomia
and others
On their own
complex
evolutionary paths
Echinoderms (sea urchin)
Hemichordata (acorn worms)
the vertebrates
Chordata (tunicates, lancelet, fish, human)
Porifera, Cnidaria, Ctenophora
(sponges, corals, comb jellies)
Unicellular organisms
Lophotrochozoa
Molluscs
and others
Protostomia
Annelids
and others
Nematodes
Bilateria
and others
Arthropods
Ecdysozoa
Metazoa
Deuterostomia
and others
Echinoderms (sea urchin)
Hemichordata (acorn worms)
the vertebrates
Chordata (tunicates, lancelet, fish, human)
Porifera, Cnidaria, Ctenophora
(sponges, corals, comb jellies)
Unicellular organisms
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.
(Domazet-Loso and T autz, 2008)
Origin of Human Genes/Genes Associated with Human Genetic Disease
(1,760/22,937)
10,000
Genome
Animals
Disease
Gene Number
1,000
Primates
Mammals
Jawed
Vertebrates
100
10
1
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Phylostrata
(Domazet-Loso and T autz, 2008)
Origin of Human Genes/Genes Associated with Human Genetic Disease
(1,760/22,937)
10,000
Genome
Animals
Disease
Gene Number
1,000
Primates
Mammals
Jawed
Vertebrates
100
Genes involved in genetic disease
are biased toward ancient genes.
10
1
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Phylostrata
(Domazet-Loso and T autz, 2008)
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?
Origin of Human Genes/Genes Associated with Human Genetic Disease
10,000
Genome
Animals
Disease
Principally immune-related
Gene Number
1,000
Principally
signaling
Mammals
Jawed
Vertebrates
100
Overrepresented in
immune-related
Overrepresented in
cell-cell
communication
10
1
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Phylostrata
(Domazet-Loso and T autz, 2008)
Insights into human biology
Bioinformatic approaches to evolution of animals
Models of animal-bacterial associations - an evolutionary tool kit
“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 T autz, 2008]
Environmental context for the evolution of animal body plans - what drove selection on the mucosa?
Lophotrochozoa
Molluscs
and others
Protostomia
Annelids
and others
Nematodes
Bilateria
and others
Arthropods
Ecdysozoa
Metazoa
Deuterostomia
and others
Echinoderms (sea urchin)
Hemichordata (acorn worms)
the vertebrates
Chordata (tunicates, lancelet, fish, human)
Porifera, Cnidaria, Ctenophora
(sponges, corals, comb jellies)
Unicellular organisms
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 preventing
overgrowth of their tissues by the microorganisms that
share the nutrient pool
Milestones in animal evolution
mollusks
insects
vertebrates
coelom
complete gut
bilateral
flatworms
ribbonworms
(triploblastic - +mesoderm)
tissue layers
(diploblastic - endoderm/ectoderm)
multicellularity
anemones
sponges
Milestones in animal evolution
mollusks
GUT SEPARATED FROM
BODY WALL insects
vertebrates
coelom
INTERNAL TISSUE
LA YERS, ORGANS
one-way digestion,
GUT REGIONALIZATION
complete gut
bilateral
flatworms
ribbonworms
(triploblastic - +mesoderm)
tissue layers
EPITHELIA
(diploblastic - endoderm/ectoderm)
multicellularity
anemones
sponges
Thomas Bosch
Christian-Albrechts University
Kiel, Germany
Hydra spp.
Many responses of animals
to the microbial world are
ancient and conserved.
HydraHydra
has two
epidermis
(derived from
– a cell
newlayers
model- in
innate immunity
ectoderm) and gastrodermis (derived from endoderm)
Human small intestine
www.visualsunlimited.com/requestform.jsp
Hydra body column
Hydra frozen section EM, TCG Bosch
Analysis of bacteria associated with
different Hydra species
Fraune & Bosch (2007) Proc.Natl.Acad.Sci USA
Fraune & Bosch (2009) Microbe
Fraune & Bosch (2010) BioEssays
Fraune et al (2010) Proc.Natl.Acad.Sci USA
Analysis of bacteria associated with
different Hydra species
Environmental isolates &
long-term lab cultures
Fraune & Bosch (2007) Proc.Natl.Acad.Sci USA
Fraune & Bosch (2009) Microbe
Fraune & Bosch (2010) BioEssays
Fraune et al (2010) Proc.Natl.Acad.Sci USA
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.
CENOZOIC
Quaternary
Tertiary
MESOZOIC
Water-to-Land
Transition
Millions of
years ago
Radiation of members
of 7 of the ~36 animal phyla,
(representatives in all
three subkingdoms)
Homo sapiens
65
Cretaceous
Jurassic
Triassic
earliest
mammals
225
Permian
Carboniferous
earliest
tetrapods
first evidence
PALEOZOIC
Devonian
Deuterostomia
Silurian
Ecdysozoa
Ordovician
Cambrian
Lophotrochozoa
earliest jawed
vertebrates
earliest vertebrates
550
ALL animal body
plans diverged
Most vertebrates are aquatic.
Agnatha (80)
Chondrichthys (900)
Mammalia
(4500)
Mam
mals
Aves
(9100)
Bir
ds
Actinopterygii (25,000)
Lepidosauria
(6800)
h ibia
Amp
R
ep
Crocodilia (22)
ns
til
es
Fishes
Anura
(4300)
Testudinia
(260)
Gymnophiona
(165)
Actinistia + Dipnoi (8)
Urodeles (415)
Water-to-Land Transition
Land animals [and plants] require mechanisms:
of structural support
to respire
to reproduce
to avoid desiccation
Water-to-Land Transition
Land animals [and plants] require mechanisms:
of structural support
to respire
to reproduce
to avoid desiccation
require substantial remodeling
of the mucosa
mucosal immune
system
epithelium
bacterial consortium
Microbiota
MacPherson & Harris (2004) Nat Rev Immunol
The integration of microbiology
and host biology
= a revolution in biology
Our concept of the nature
of the immune system
CENOZOIC
MESOZOIC
mya
Homo sapiens
Quaternary
T ertiary
65
Cretaceous
Jurassic
Triassic
earliest mammals
225
Permian
Carboniferous
earliest tetrapods
PALEOZOIC
Devonian
Deuterostomia
Silurian
Ecdysozoa
Ordovician
Cambrian
Lophotrochozoa
adaptive
immune
system
earliest jawed
vertebrates
550
ALL animal body
plans diverged
earliest vertebrates
Invertebrates - 96%
Vertebrates - 4%
Agnathan
(jawless)
Gnathostome
(jawed)
Agnatha
Cartilagenous
fishes (sharks, rays)
Ecdysozoa
Deuterostomia
Echinodermata
Chordata
Lophotrochozoa
Porifera
(sponges)
Bony fishes
Cephalochordata
Vertebrata
Amphibians
Urochordata
Reptiles
Birds
Mammals
The mechanism enabling somatic recombination appears
at the agnathan - gnathostome transition.
Basic differences in immunity between invertebrates and
vertebrates may reflect the way they interact with microbes:
Invertebrates Vertebrates
Binary associations
intra- or extracellular
Stable, coevolved,
consortial symbioses
Correlated immunity:
common
rare
innate only
rare
common
innate + adaptive
Basic differences in immunity between invertebrates and
vertebrates may reflect the way they interact with microbes:
Invertebrates Vertebrates
Binary associations
intra- or extracellular
Stable, coevolved,
consortial symbioses
Correlated immunity:
common
rare
innate only
rare
common
innate + adaptive
Could a principal selection pressure on the evolution of the vertebrate
adaptive immune system be the requirement of the host to maintain
coevolved communities in balance?
INVERTEBRATES
VERTEBRATES
Association with
microorganisms
restrictive
permissive
Immune system:
selection on,
and function of
non-self
recognition
control of a set
of communities
mucosal immune
system
epithelium
bacterial consortium
Microbiota
MacPherson & Harris (2004) Nat Rev Immunol
Conclusions
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).
Thank you!
Questions?