Microbiomes in Agriculture, Food, Health and the Environment

Microbiomes
in Agriculture, Food, Health
and the Environment
UIC Fall 2015 Meeting
October 27, 2015
Jonathan A. Eisen
@phylogenomics
University of California, Davis

Panel 2
Impacts of Human and Animal
Microbiomes on Food and Human Health
Moderator: Danielle Barille
Talk 1: Angela Zivcovik
Talk 2: Neil Stollman

Panel 3
Impacts of Microbiomes on Plants and
Agriculture
Moderator: Sue Turner,
Talk 1: Venkatesan (Sundar) Sundaresan
Talk 2: Nic Everett

Panel 4
Impacts of Microbiomes on the
Environment
Moderator: Jonathan Eisen
Talk 1: Jessica Green
Talk 2: Susan Lynch

microBIOME or microbiOME?
• microbi-OME
• collection of genomes of microbes from a
community (emphasis on OME)
• micro-BIOME
• a community of microbes (emphasis on
BIOME)
• see http://tinyurl.com/definemicrobiome

The Rise of the Microbiome
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Pubmed Hits to Microbiome vs. Year

Google Trends Hits to Microbiome
The Rise of the Microbiome

Why Now I: Appreciation of Microbial Diversity
Functional Diversity
Diversity of Form
Phylogenetic Diversity
MICROBES
RUN THE
PLANET

Why Now II: Post Genome Blues
The Microbiome
Transcriptome
VariomeEpigenome
Overselling the Human Genome?

Why Now III: Sequencing Has Gone Crazy

<<<<
Culturing Observation
CountCount
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sa=i&rct=j&q=&esrc=s&source=images&
cd=&docid=rLu5sL207WlE1M&tbnid=CR
LQYP7d9d_TcM:&ved=0CAUQjRw&url=h
ttp%3A%2F%2Fwww.biol.unt.edu
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U_TyCtOqsQSu9YGwBg&psig=AFQjCN
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yHFG2KPuBZt8kIPw&ust=140487395121
1424
DNA
Why Now III: Culture Independent Studies

Turnbaugh et al Nature. 2006 444(7122):1027-31.
Why Now IV: Microbiome Functions

HUMAN
MICROBIOME
YOUR BODY: HUMAN AND MICROBES
Learn more about your microbiome
American Academy of Microbiology:
http://bit.ly/HumanMicrobiome
fungal
bacterial
human
WHOʼS THERE?
A human body is actually only
about 25% human cells. The
rest is many thousands of
species of bacteria and other
microbes.
Cells in the
human body:
WHERE ARE THEY? WHAT ARE THEY DOING?
Wherever the human body is exposed to
the outside world, there is a microbial
community.
skinGI tractlungsmouth
Our microbiome helps us extract energy
and nutrients from the food we eat,
and crowds out or inhibits pathogens.
HOW DO WE GET OUR MICROBIOME?
BIRTH:
A newborn gets its
microbes from:
BREAST MILK:
Breast milk has been fine-
tuned over millions of
years to provide:
ENVIRONMENT:
For the rest of the baby’s life, it
will continuously encounter new
microbes from:
soil and water
people, pets, plants
new and diverse
foods
nutrients, vitamins,
and antibodies
diverse microbes to
populate the baby’s
gut
its mother’s birth
canal
skin of its mother
and other care-
givers
WHAT IS THE MICROBIOME? WAIT ... WHATʼS A MICROBE?
The human body is home to
trillions of microbes. The
community of microbes
living in intimate association
with our bodies, and the genes
they contain, make up the
human microbiome.
A microbe is a microscopic organism - this
includes viruses, bacteria, and fungi.
Not all microbes make us sick - the microbes in
and on our bodies play many essential roles.
2.5lb
2.5 LBS = WEIGHT
of the microbiome
3 PINTS = VOLUME
of the microbiome
Viruses outnumber bacteria
by about 5:1.
5 1:99%
Microbes contribute an extra
2,000,000 genes to the 20,000 gene
human genome.
urogenital
tract
HUMAN
MICROBIOME
fungal
bacterial
human
WHOʼS THERE?
microbes.
Cells in the
human body:
community.
BIRTH:
A newborn gets its
microbes from:
BREAST MILK:
years to provide:
ENVIRONMENT:
microbes from:
soil and water
new and diverse
foods
and antibodies
diverse microbes to
gut
canal
skin of its mother
and other care-
givers
human microbiome.
2.5lb
2.5 LBS = WEIGHT
of the microbiome
3 PINTS = VOLUME
of the microbiome
by about 5:1.
5 1:99%
human genome.
urogenital
tract
HUMAN
MICROBIOME
fungal
bacterial
human
WHOʼS THERE?
microbes.
Cells in the
human body:
community.
BIRTH:
A newborn gets its
microbes from:
BREAST MILK:
years to provide:
ENVIRONMENT:
microbes from:
soil and water
new and diverse
foods
and antibodies
diverse microbes to
gut
canal
skin of its mother
and other care-
givers
human microbiome.
2.5lb
2.5 LBS = WEIGHT
of the microbiome
3 PINTS = VOLUME
of the microbiome
by about 5:1.
5 1:99%
human genome.
urogenital
tract
HUMAN
MICROBIOME
fungal
bacterial
human
WHOʼS THERE?
microbes.
Cells in the
human body:
community.
BIRTH:
A newborn gets its
microbes from:
BREAST MILK:
years to provide:
ENVIRONMENT:
microbes from:
soil and water
new and diverse
foods
and antibodies
diverse microbes to
gut
canal
skin of its mother
and other care-
givers
human microbiome.
2.5lb
2.5 LBS = WEIGHT
of the microbiome
3 PINTS = VOLUME
of the microbiome
by about 5:1.
5 1:99%
human genome.
urogenital
tract
HUMAN
MICROBIOME
fungal
bacterial
human
WHOʼS THERE?
microbes.
Cells in the
human body:
community.
BIRTH:
A newborn gets its
microbes from:
BREAST MILK:
years to provide:
ENVIRONMENT:
microbes from:
soil and water
new and diverse
foods
and antibodies
diverse microbes to
gut
canal
skin of its mother
and other care-
givers
human microbiome.
2.5lb
2.5 LBS = WEIGHT
of the microbiome
3 PINTS = VOLUME
of the microbiome
by about 5:1.
5 1:99%
human genome.
urogenital
tract
HUMAN
MICROBIOME
fungal
bacterial
human
WHOʼS THERE?
microbes.
Cells in the
human body:
community.
BIRTH:
A newborn gets its
microbes from:
BREAST MILK:
years to provide:
ENVIRONMENT:
microbes from:
soil and water
new and diverse
foods
and antibodies
diverse microbes to
gut
canal
skin of its mother
and other care-
givers
human microbiome.
2.5lb
2.5 LBS = WEIGHT
of the microbiome
3 PINTS = VOLUME
of the microbiome
by about 5:1.
5 1:99%
human genome.
urogenital
tract
HUMAN
MICROBIOME
fungal
bacterial
human
WHOʼS THERE?
microbes.
Cells in the
human body:
community.
BIRTH:
A newborn gets its
microbes from:
BREAST MILK:
years to provide:
ENVIRONMENT:
microbes from:
soil and water
new and diverse
foods
and antibodies
diverse microbes to
gut
canal
skin of its mother
and other care-
givers
human microbiome.
2.5lb
2.5 LBS = WEIGHT
of the microbiome
3 PINTS = VOLUME
of the microbiome
by about 5:1.
5 1:99%
human genome.
urogenital
tract
HUMAN
MICROBIOME
fungal
bacterial
human
WHOʼS THERE?
microbes.
Cells in the
human body:
community.
BIRTH:
A newborn gets its
microbes from:
BREAST MILK:
years to provide:
ENVIRONMENT:
microbes from:
soil and water
new and diverse
foods
and antibodies
diverse microbes to
gut
canal
skin of its mother
and other care-
givers
human microbiome.
2.5lb
2.5 LBS = WEIGHT
of the microbiome
3 PINTS = VOLUME
of the microbiome
by about 5:1.
5 1:99%
human genome.
urogenital
tract
HUMAN
MICROBIOME
fungal
bacterial
human
WHOʼS THERE?
microbes.
Cells in the
human body:
community.
BIRTH:
A newborn gets its
microbes from:
BREAST MILK:
years to provide:
ENVIRONMENT:
microbes from:
soil and water
new and diverse
foods
and antibodies
diverse microbes to
gut
canal
skin of its mother
and other care-
givers
human microbiome.
2.5lb
2.5 LBS = WEIGHT
of the microbiome
3 PINTS = VOLUME
of the microbiome
by about 5:1.
5 1:99%
human genome.
urogenital
tract
HUMAN
MICROBIOME
fungal
bacterial
human
WHOʼS THERE?
microbes.
Cells in the
human body:
community.
BIRTH:
A newborn gets its
microbes from:
BREAST MILK:
years to provide:
ENVIRONMENT:
microbes from:
soil and water
new and diverse
foods
and antibodies
diverse microbes to
gut
canal
skin of its mother
and other care-
givers
human microbiome.
2.5lb
2.5 LBS = WEIGHT
of the microbiome
3 PINTS = VOLUME
of the microbiome
by about 5:1.
5 1:99%
human genome.
urogenital
tract
HUMAN
MICROBIOME
fungal
bacterial
human
WHOʼS THERE?
microbes.
Cells in the
human body:
community.
BIRTH:
A newborn gets its
microbes from:
BREAST MILK:
years to provide:
ENVIRONMENT:
microbes from:
soil and water
new and diverse
foods
and antibodies
diverse microbes to
gut
canal
skin of its mother
and other care-
givers
human microbiome.
2.5lb
2.5 LBS = WEIGHT
of the microbiome
3 PINTS = VOLUME
of the microbiome
by about 5:1.
5 1:99%
human genome.
urogenital
tract
HUMAN
MICROBIOME
fungal
bacterial
human
WHOʼS THERE?
microbes.
Cells in the
human body:
community.
BIRTH:
A newborn gets its
microbes from:
BREAST MILK:
years to provide:
ENVIRONMENT:
microbes from:
soil and water
new and diverse
foods
and antibodies
diverse microbes to
gut
canal
skin of its mother
and other care-
givers
human microbiome.
2.5lb
2.5 LBS = WEIGHT
of the microbiome
3 PINTS = VOLUME
of the microbiome
by about 5:1.
5 1:99%
human genome.
urogenital
tract
HUMAN
MICROBIOME
fungal
bacterial
human
WHOʼS THERE?
microbes.
Cells in the
human body:
community.
BIRTH:
A newborn gets its
microbes from:
BREAST MILK:
years to provide:
ENVIRONMENT:
microbes from:
soil and water
new and diverse
foods
and antibodies
diverse microbes to
gut
canal
skin of its mother
and other care-
givers
human microbiome.
2.5lb
2.5 LBS = WEIGHT
of the microbiome
3 PINTS = VOLUME
of the microbiome
by about 5:1.
5 1:99%
human genome.
urogenital
tract
HU
MICROBI
YOUR BODY: HUMAN AND M
Learn more about your micro
fungal
bacterial
human
WHOʼS THERE?
A human bod
about 25% h
rest is many t
species of ba
microbes.
Cells in the
human body:
WHERE ARE THEY? WHAT ARE THE
community.
GI tractlungsmouth
Our microbi
and nu
and crowd
HOW DO WE GET OUR MICROB
BIRTH:
A newborn gets its
microbes from:
BREAST MILK:
years to provide:
ENV
For t
will c
micro
s
p
n
fo
and antibodies
diverse microbes to
gut
canal
skin of its mother
and other care-
givers
WHAT IS THE MICROBIOME? WAIT ... WH
human microbiome.
A microbe is a mic
includes viruses, b
Not all microbes m
and on our bodies
2.5lb
2.5 LBS = WEIGHT
of the microbiome
Viru
599%
human genome.
HUMAN
MICROBIOME
fungal
bacterial
human
WHOʼS THERE?
microbes.
Cells in the
human body:
community.
BIRTH:
A newborn gets its
microbes from:
BREAST MILK:
years to provide:
ENVIRONMENT:
microbes from:
soil and water
new and diverse
foods
and antibodies
diverse microbes to
gut
canal
skin of its mother
and other care-
givers
human microbiome.
2.5lb
2.5 LBS = WEIGHT
of the microbiome
3 PINTS = VOLUME
of the microbiome
by about 5:1.
5 1:99%
human genome.
urogenital
tract
HU
MICROBI
fungal
bacterial
human
WHOʼS THERE?
A human bod
about 25% h
rest is many t
species of ba
microbes.
Cells in the
human body:
community.
GI tractlungsmouth
Our microbi
and nu
and crowd
BIRTH:
A newborn gets its
microbes from:
BREAST MILK:
years to provide:
ENV
For t
will c
micro
s
p
n
fo
and antibodies
diverse microbes to
gut
canal
skin of its mother
and other care-
givers
human microbiome.
A microbe is a mic
includes viruses, b
Not all microbes m
and on our bodies
2.5lb
2.5 LBS = WEIGHT
of the microbiome
Viru
599%
human genome.
HUMAN
MICROBIOME
fungal
bacterial
human
WHOʼS THERE?
microbes.
Cells in the
human body:
community.
BIRTH:
A newborn gets its
microbes from:
BREAST MILK:
years to provide:
ENVIRONMENT:
microbes from:
soil and water
new and diverse
foods
and antibodies
diverse microbes to
gut
canal
skin of its mother
and other care-
givers
human microbiome.
2.5lb
2.5 LBS = WEIGHT
of the microbiome
3 PINTS = VOLUME
of the microbiome
by about 5:1.
5 1:99%
human genome.
urogenital
tract
HUM
MICROBI
fungal
bacterial
human
WHOʼS THERE?
A human bod
about 25% hu
rest is many t
species of bac
microbes.
Cells in the
human body:
community.
GI tractlungsmouth
Our microbio
and nut
and crowd
BIRTH:
A newborn gets its
microbes from:
BREAST MILK:
years to provide:
ENV
For th
will c
micro
so
pe
ne
fo
and antibodies
diverse microbes to
gut
canal
skin of its mother
and other care-
givers
human microbiome.
A microbe is a mic
includes viruses, ba
Not all microbes m
and on our bodies
2.5lb
2.5 LBS = WEIGHT
of the microbiome
Viru
599%
human genome.
HUMAN
MICROBIOME
fungal
bacterial
human
WHOʼS THERE?
microbes.
Cells in the
human body:
community.
BIRTH:
A newborn gets its
microbes from:
BREAST MILK:
years to provide:
ENVIRONMENT:
microbes from:
soil and water
new and diverse
foods
and antibodies
diverse microbes to
gut
canal
skin of its mother
and other care-
givers
human microbiome.
2.5lb
2.5 LBS = WEIGHT
of the microbiome
3 PINTS = VOLUME
of the microbiome
by about 5:1.
5 1:99%
human genome.
urogenital
tract
HUMAN
MICROBIOME
fungal
bacterial
human
WHOʼS THERE?
microbes.
Cells in the
human body:
community.
BIRTH:
A newborn gets its
microbes from:
BREAST MILK:
years to provide:
ENVIRONMENT:
microbes from:
soil and water
new and diverse
foods
and antibodies
diverse microbes to
gut
canal
skin of its mother
and other care-
givers
human microbiome.
2.5lb
2.5 LBS = WEIGHT
of the microbiome
3 PINTS = VOLUME
of the microbiome
by about 5:1.
5 1:99%
human genome.
urogenital
tract
HUMAN
MICROBIOME
fungal
bacterial
human
WHOʼS THERE?
microbes.
Cells in the
human body:
community.
BIRTH:
A newborn gets its
microbes from:
BREAST MILK:
years to provide:
ENVIRONMENT:
microbes from:
soil and water
new and diverse
foods
and antibodies
diverse microbes to
gut
canal
skin of its mother
and other care-
givers
human microbiome.
2.5lb
2.5 LBS = WEIGHT
of the microbiome
3 PINTS = VOLUME
of the microbiome
by about 5:1.
5 1:99%
human genome.
urogenital
tract
HUMAN
MICROBIOME
fungal
bacterial
human
WHOʼS THERE?
microbes.
Cells in the
human body:
community.
BIRTH:
A newborn gets its
microbes from:
BREAST MILK:
years to provide:
ENVIRONMENT:
microbes from:
soil and water
new and diverse
foods
and antibodies
diverse microbes to
gut
canal
skin of its mother
and other care-
givers
human microbiome.
2.5lb
2.5 LBS = WEIGHT
of the microbiome
3 PINTS = VOLUME
of the microbiome
by about 5:1.
5 1:99%
human genome.
urogenital
tract
HUMAN
MICROBIOME
fungal
bacterial
human
WHOʼS THERE?
microbes.
Cells in the
human body:
community.
BIRTH:
A newborn gets its
microbes from:
BREAST MILK:
years to provide:
ENVIRONMENT:
microbes from:
soil and water
new and diverse
foods
and antibodies
diverse microbes to
gut
canal
skin of its mother
and other care-
givers
human microbiome.
2.5lb
2.5 LBS = WEIGHT
of the microbiome
3 PINTS = VOLUME
of the microbiome
by about 5:1.
5 1:99%
human genome.
urogenital
tract
HUM
MICROBI
fungal
bacterial
human
WHOʼS THERE?
A human bod
about 25% hu
rest is many t
species of bac
microbes.
Cells in the
human body:
community.
GI tractlungsmouth
Our microbio
and nut
and crowd
BIRTH:
A newborn gets its
microbes from:
BREAST MILK:
years to provide:
ENV
For th
will c
micro
so
pe
ne
fo
and antibodies
diverse microbes to
gut
canal
skin of its mother
and other care-
givers
human microbiome.
A microbe is a mic
includes viruses, ba
Not all microbes m
and on our bodies
2.5lb
2.5 LBS = WEIGHT
of the microbiome
Viru
599%
human genome.
Challenge 1: Complexity
Microbial Diversity
Microbial Diversity2 Fragmented Data
Host Variation
Functional
Diversity

Challenge 2: Public Understanding
Germophobia Microbiomania

Abstract
Glyphosate, the active ingredient in Roundup®, is the most popular
herbicide used worldwide. The industry asserts it is minimally toxic to
humans, but here we argue otherwise. Residues are found in the main
foods of the Western diet, comprised primarily of sugar, corn, soy and
wheat. Glyphosate's inhibition of cytochrome P450 (CYP) enzymes is an
overlooked component of its toxicity to mammals. CYP enzymes play
crucial roles in biology, one of which is to detoxify xenobiotics. Thus,
glyphosate enhances the damaging effects of other food borne chemical
residues and environmental toxins. Negative impact on the body is
insidious and manifests slowly over time as inflammation damages cellular
systems throughout the body. Here, we show how interference with CYP
enzymes acts synergistically with disruption of the biosynthesis of
aromatic amino acids by gut bacteria, as well as impairment in serum
sulfate transport. Consequences are most of the diseases and conditions
associated with a Western diet, which include gastrointestinal disorders,
obesity, diabetes, heart disease, depression, autism, infertility, cancer and
Alzheimer’s disease. We explain the documented effects of glyphosate and
its ability to induce disease, and we show that glyphosate is the “textbook
example” of exogenous semiotic entropy: the disruption of homeostasis by
environmental toxins.

Dealing w/ Complexity 1: 
 
rRNA Surveys

Archaea
Worse Classification of Cultured Taxa by rRNA
rRNA rRNArRNA
ACUGC
ACCUAU
CGUUCG
ACUCC
AGCUAU
CGAUCG
ACCCC
AGCUCU
CGCUCG
Taxa Characters
S ACUGCACCUAUCGUUCG
R ACUCCACCUAUCGUUCG
E ACUCCAGCUAUCGAUCG
F ACUCCAGGUAUCGAUCG
C ACCCCAGCUCUCGCUCG
W ACCCCAGCUCUGGCUCG
EukaryotesBacteria
Carl
Woese

rRNA Phylotyping: One Taxon
DNA
ACTGC
ACCTAT
CGTTCG
ACTGC
ACCTAT
CGTTCG
ACTGC
ACCTAT
CGTTCG
Taxa Characters
B1 ACTGCACCTATCGTTCG
B2 ACTCCACCTATCGTTCG
E1 ACTCCAGCTATCGATCG
E2 ACTCCAGGTATCGATCG
A1 ACCCCAGCTCTCGCTCG
A2 ACCCCAGCTCTGGCTCG
New1 ACTGCACCTATCGTTCG
EukaryotesBacteria Archaea
Many
sequences
from one
sample all
point to the
same branch
on the tree
Norm
Pace

DNA
ACTGC
ACCTAT
CGTTCG
ACTGC
ACCTAT
CGTTCG
ACCCC
AGCTCT
CGCTCG
Taxa Characters
New1 ACCCCAGCTCTGCCTCG
One can
estimate cell
counts from
the number of
times each
sequence is
seen.
rRNA Phylotyping: Two Taxa

DNA
Taxa Characters
New2 AGGGGAGCTCTGCCTCG
New3 ACTCCAGCTATCGATCG
ACTGC
ACCTAT
CGTTCG
ACTCC
AGCTAT
CGATCG
ACCCC
AGCTCT
CGCTCG
AGGGG
AGCTCT
CGCTCG
AGGGG
AGCTCT
CGCTCG
ACTGC
ACCTAT
CGTTCG
Even with
more taxa it
still works
rRNA Phylotyping: Many Taxa

rRNA Phylotyping: Relative Abundance
DNA
Taxa Characters
ACTGC
ACCTAT
CGTTCG
ACTCC
AGCTAT
CGATCG
ACCCC
AGCTCT
CGCTCG
AGGGG
AGCTCT
CGCTCG
AGGGG
AGCTCT
CGCTCG
ACTGC
ACCTAT
CGTTCG
Even with
more taxa it
still works

DNA DNADNA
ACTGC
ACCTAT
CGTTCG
ACTCC
AGCTAT
CGATCG
ACCCC
AGCTCT
CGCTCG
Taxa Characters
New2 ACGGCAGCTCTGCCTCG
rRNA PCR: Community Comparisons

Dealing with Complexity 2: 
 
Metagenomics

Metagenomics
metagenomics
ACUGC
ACCUAU
CGUUCG
ACUCC
AGCUAU
CGAUCG
ACCCC
AGCUCU
CGCUCG
Taxa Characters
S ACUGCACCUAUCGUUCG
R ACUCCACCUAUCGUUCG
E ACUCCAGCUAUCGAUCG
F ACUCCAGGUAUCGAUCG
C ACCCCAGCUCUCGCUCG
W ACCCCAGCUCUGGCUCG
Taxa Characters
S ACUGCACCUAUCGUUCG
E ACUCCAGCUAUCGAUCG
C ACCCCAGCUCUCGCUCG

Eisen et al.
1992
Phylotyping vs. Function
Genomic Variation w/in Species

Culture Independent “Metagenomics”
DNA DNADNA
Taxa Characters
RecA RecARecA
http://genomebiology.com/2008/9/10/R151 Genome Biology 2008, Volume 9, Issue 10, Article R151 Wu and Eisen R151.7
Genome Biology 2008, 9:R151
sequences are not conserved at the nucleotide level [29]. As a
result, the nr database does not actually contain many more
protein marker sequences that can be used as references than
those available from complete genome sequences.
Comparison of phylogeny-based and similarity-based phylotyping
Although our phylogeny-based phylotyping is fully auto-
mated, it still requires many more steps than, and is slower
than, similarity based phylotyping methods such as a
MEGAN [30]. Is it worth the trouble? Similarity based phylo-
typing works by searching a query sequence against a refer-
ence database such as NCBI nr and deriving taxonomic
information from the best matches or 'hits'. When species
that are closely related to the query sequence exist in the ref-
erence database, similarity-based phylotyping can work well.
However, if the reference database is a biased sample or if it
contains no closely related species to the query, then the top
hits returned could be misleading [31]. Furthermore, similar-
ity-based methods require an arbitrary similarity cut-off
value to define the top hits. Because individual bacterial
genomes and proteins can evolve at very different rates, a uni-
versal cut-off that works under all conditions does not exist.
As a result, the final results can be very subjective.
In contrast, our tree-based bracketing algorithm places the
query sequence within the context of a phylogenetic tree and
only assigns it to a taxonomic level if that level has adequate
sampling (see Materials and methods [below] for details of
the algorithm). With the well sampled species Prochlorococ-
cus marinus, for example, our method can distinguish closely
related organisms and make taxonomic identifications at the
species level. Our reanalysis of the Sargasso Sea data placed
672 sequences (3.6% of the total) within a P. marinus clade.
On the other hand, for sparsely sampled clades such as
Aquifex, assignments will be made only at the phylum level.
Thus, our phylogeny-based analysis is less susceptible to data
sampling bias than a similarity based approach, and it makes
Major phylotypes identified in Sargasso Sea metagenomic dataFigure 3
Major phylotypes identified in Sargasso Sea metagenomic data. The metagenomic data previously obtained from the Sargasso Sea was reanalyzed using
AMPHORA and the 31 protein phylogenetic markers. The microbial diversity profiles obtained from individual markers are remarkably consistent. The
breakdown of the phylotyping assignments by markers and major taxonomic groups is listed in Additional data file 5.
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
Alphaproteobacteria
Betaproteobacteria
G
am
m
aproteobacteria
D
eltaproteobacteria
Epsilonproteobacteria
U
nclassified
proteobacteria
Bacteroidetes
C
hlam
ydiae
C
yanobacteria
Acidobacteria
Therm
otogae
Fusobacteria
ActinobacteriaAquificae
Planctom
ycetes
Spirochaetes
Firm
icutes
C
hloroflexiC
hlorobi
U
nclassified
bacteria
dnaG
frr
infC
nusA
pgk
pyrG
rplA
rplB
rplC
rplD
rplE
rplF
rplK
rplL
rplM
rplN
rplP
rplS
rplT
rpmA
rpoB
rpsB
rpsC
rpsE
rpsI
rpsJ
rpsK
rpsM
rpsS
smpB
tsf
Relativeabundance
RpoB RpoBRpoB
Rpl4 Rpl4Rpl4 rRNA rRNArRNA
Hsp70 Hsp70Hsp70
EFTu EFTuEFTu
Many other genes
better than rRNA

inputs of fixed carbon or nitrogen from external sources. As with
Leptospirillum group I, both Leptospirillum group II and III have the
genes needed to fix carbon by means of the Calvin–Benson–
Bassham cycle (using type II ribulose 1,5-bisphosphate carboxy-
lase–oxygenase). All genomes recovered from the AMD system
contain formate hydrogenlyase complexes. These, in combination
with carbon monoxide dehydrogenase, may be used for carbon
fixation via the reductive acetyl coenzyme A (acetyl-CoA) pathway
by some, or all, organisms. Given the large number of ABC-type
sugar and amino acid transporters encoded in the Ferroplasma type
Figure 4 Cell metabolic cartoons constructed from the annotation of 2,180 ORFs
identified in the Leptospirillum group II genome (63% with putative assigned function) and
1,931 ORFs in the Ferroplasma type II genome (58% with assigned function). The cell
cartoons are shown within a biofilm that is attached to the surface of an acid mine
drainage stream (viewed in cross-section). Tight coupling between ferrous iron oxidation,
pyrite dissolution and acid generation is indicated. Rubisco, ribulose 1,5-bisphosphate
carboxylase–oxygenase. THF, tetrahydrofolate.
articles
NATURE | doi:10.1038/nature02340 | www.nature.com/nature 5©2004 NaturePublishing Group
Metagenomics
metagenomics
ACUGC
ACCUAU
CGUUCG
ACUCC
AGCUAU
CGAUCG
ACCCC
AGCUCU
CGCUCG
Taxa Characters
S ACUGCACCUAUCGUUCG
R ACUCCACCUAUCGUUCG
E ACUCCAGCUAUCGAUCG
F ACUCCAGGUAUCGAUCG
C ACCCCAGCUCUCGCUCG
W ACCCCAGCUCUGGCUCG

 
Linking Taxa to Functions Critical

Transfer of 34
S from SRB to PSB
12
C, 12
C14
N, 32
S
Biomass
(RGB composite)
0.044 0.080
34S-incorporation
(34S/32S ratio)
Wilbanks, E.G. et al (2014). Environmental Microbiology
Lizzy Wilbanks
@lizzywilbanks

 
Reference Data Very Limited

2007-2014: GEBA
Figure from Barton, Eisen et al. “Evolution”, CSHL Press based on Baldauf et al Tree

The Dark Matter of Biology
From Wu et al. 2009 Nature 462, 1056-1060

JGI Dark Matter Project
environmental
samples (n=9)
isolation of single
cells (n=9,600)
whole genome
amplification (n=3,300)
SSU rRNA gene
based identification
(n=2,000)
genome sequencing,
assembly and QC (n=201)
draft genomes
(n=201)
SAK
HSM ETLTG
HOT
GOM
GBS
EPR
TAETL T
PR
EBS
AK E
SM G TATTG
OM
OT
seawater brackish/freshwater hydrothermal sediment bioreactor
GN04
WS3 (Latescibacteria)
GN01
+Gí
LD1
WS1
Poribacteria
BRC1
Lentisphaerae
Verrucomicrobia
OP3 (Omnitrophica)
Chlamydiae
Planctomycetes
NKB19 (Hydrogenedentes)
WYO
Armatimonadetes
WS4
Actinobacteria
Gemmatimonadetes
NC10
SC4
WS2
Cyanobacteria
:36í2
Deltaproteobacteria
EM19 (Calescamantes)
2FW6SDí )HUYLGLEDFWHULD

GAL35
Aquificae
EM3
Thermotogae
Dictyoglomi
SPAM
GAL15
CD12 (Aerophobetes)
OP8 (Aminicenantes)
AC1
SBR1093
Thermodesulfobacteria
Deferribacteres
Synergistetes
OP9 (Atribacteria)
:36í2
Caldiserica
AD3
Chloroflexi
Acidobacteria
Elusimicrobia
Nitrospirae
49S1 2B
Caldithrix
GOUTA4
6$5 0DULQLPLFURELD

Chlorobi
)LUPLFXWHV
Tenericutes
)XVREDFWHULD
Chrysiogenetes
Proteobacteria
)LEUREDFWHUHV
TG3
Spirochaetes
WWE1 (Cloacamonetes)
70
ZB3
093í
'HLQRFRFFXVí7KHUPXV
OP1 (Acetothermia)
Bacteriodetes
TM7
GN02 (Gracilibacteria)
SR1
BH1
OD1 (Parcubacteria)
:6
OP11 (Microgenomates)
Euryarchaeota
Micrarchaea
DSEG (Aenigmarchaea)
Nanohaloarchaea
Nanoarchaea
Cren MCG
Thaumarchaeota
Cren C2
Aigarchaeota
Cren pISA7
Cren Thermoprotei
Korarchaeota
pMC2A384 (Diapherotrites)
BACTERIA ARCHAEA
archaeal toxins (Nanoarchaea)
lytic murein transglycosylase
stringent response
(Diapherotrites, Nanoarchaea)
ppGpp
limiting
amino acids
SpotT RelA
(GTP or GDP)
+ PPi
GTP or GDP
+ATP
limiting
phosphate,
fatty acids,
carbon, iron
DksA
Expression of components
for stress response
sigma factor (Diapherotrites, Nanoarchaea)
ı4
ȕ ȕ¶
ı2ı3 ı1
-35 -10
Į17'
Į7'
51$ SROPHUDVH
oxidoretucase
+ +e- donor e- acceptor
H
1
Ribo
ADP
+
1+2
O
Reduction
Oxidation
H
1
Ribo
ADP
1+
O
2H
1$' + H 1$'++ + -
HGT from Eukaryotes (Nanoarchaea)
Eukaryota
O
+2+2
OH
1+
2+3
O
O
+2+2
1+
2+3
O
tetra-
peptide
O
+2+2
OH
1+
2+3
O
O
+2+2
1+
2+3
O
tetra-
peptide
murein (peptido-glycan)
archaeal type purine synthesis
(Microgenomates)
PurF
PurD
3XU1
PurL/Q
PurM
PurK
PurE
3XU
PurB
PurP
?
Archaea
adenine guanine
O
+ 12
+
1
1+2
1
1
H
H
1
1
1
H
H
H1 1
H
PRPP )$,$5
IMP
$,$5
A

GUA
G U
G
U
A

G
U
A U
A U
A U
Growing
AA chain
W51$*O

recognizes
UGA
P51$
UGA recoded for Gly (Gracilibacteria)
ribosome
Woyke et al. Nature 2013.
Tanja 
Woyke

 
Need to Understand Whole Systems

Mom The Microbes We Eat
PetsBuilt
Environment
Other People
Many Taxa
Coming Next … Whole Systems

Public Understanding: 
 
Outreach and Community Engagement At
Every Level is Critical

Microbiomes in Agriculture, Food, Health and the Environment

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