bis2c. biodiversity and the tree of life. 2014. l11. symbioses and the human microbiome

Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014

Lecture 11

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Lecture 11 !

Symbioses and The Human Microbiome

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BIS 002C Biodiversity & the Tree of Life

Spring 2014 !

Prof. Jonathan Eisen1


Where we are going and where we have been

• Previous Lecture: !10: Extremophiles

• Current Lecture: !11: Symbioses and humans

• Next Lecture: !12: Symbioses and humans

2

Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014 3

Please arrive early bring the following to the exam: 1. A pen 2. A #2 pencil 3. Photo ID

BIS2C Midterm 1: B SectionsApril 21st 4:10pm – 5:00pm

Freeborn Hall Last Names: A - Sak

!Chemistry 179

Last Names: San - Z


Lecture 10 Wrap

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Extreme halophiles are a monophyletic group

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Example 2: Thermophiles

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Optimal growth temperature (OGT) for Different Species

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Temperature limits

A > B >> E8

Mesophile = Optimum at moderate temps Thermophile = Optimum at 45-80°C Hyperthermophile = Optimum at > 80°C


Thermophiles found throughout the bacteria and archaea

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Uses of extremophiles

!10

Type of environment

Examples Example of mechanism of survival

Practical Uses

High temp (thermophiles)

Deep sea vents, hotsprings

Amino acid changes

Heat stable enzymes

Low temp (psychrophile)

Antarctic ocean, glaciers

Antifreeze proteins

Enhancing cold tolerance of crops

High pressure (barophile)

Deep sea vents, hotsprings

Solute changes Industrial processes

High salt (halophiles

Evaporating pools

Incr. internal osmolarity

Soy sauce production

High pH (alkaliphiles)

Soda lakes Transporters Detergents

Low pH (acidophiles)

Mine tailings Transporters Bioremediation

Desiccation (xerophiles)

Deserts Spore formation Freeze-drying additives

High radiation (radiophiles)

Nuclear reactor waste sites

Absorption, repair damage

Bioremediation, space travel


Novozymes in Davis

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Lecture 11: Symbioses and the Human Microbiome

• CSI Microbiology

• The Human Microbiome

• Ecology

• Evolution

• Don’t Oversell it

• Who are We?

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• Ecology

• Evolution


• Who are We?

13


Great Plate Count Anomaly

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Culturing Microscopy

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CountCount16



<<<<17


CountCount



Problem because appearance not

effective for “who is out there?” or “what are they

doing?”

<<<<


CountCount





doing?”

<<<<


CountCount

Solution?





doing?”

<<<<


CountCount

Solution?

DNA



Collect from environment

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CSI Microbiology (culture independent DNA studies)

Polymerase Chain Reaction- PCR

!22


DNA



DNA

ACTGC ACCTAT CGTTCG

ACTGC ACCTAT CGTTCG

ACTGC ACCTAT CGTTCG



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!



DNA

ACTGC ACCTAT CGTTCG

ACTGC ACCTAT CGTTCG

ACTGC ACCTAT CGTTCG


EukaryotesBacteria Archaea



DNA

ACTGC ACCTAT CGTTCG

ACTGC ACCTAT CGTTCG

ACTGC ACCTAT CGTTCG




Many sequences from one sample all point to the same branch on the tree


DNA



DNA


ACTGC ACCTAT CGTTCG

ACTGC ACCTAT CGTTCG

ACTGC ACCTAT CGTTCG


DNA

Taxa Characters! B1 ACTGCACCTATCGTTCG! B2 ACTCCACCTATCGTTCG! E1 ACTCCAGCTATCGATCG! E2 ACTCCAGGTATCGATCG! A1 ACCCCAGCTCTCGCTCG! A2 ACCCCAGCTCTGGCTCG! New ACCCCAGCTCTGCCTCG


ACTGC ACCTAT CGTTCG

ACTGC ACCTAT CGTTCG

ACTGC ACCTAT CGTTCG


DNA




ACTGC ACCTAT CGTTCG

ACTGC ACCTAT CGTTCG

ACTGC ACCTAT CGTTCG


DNA




ACTGC ACCTAT CGTTCG

ACTGC ACCTAT CGTTCG

ACTGC ACCTAT CGTTCG

Many sequences from one sample all point to the same branch on the tree


DNA



DNA

ACTGC ACCTAT CGTTCG

ACTGC ACCTAT CGTTCG

ACCCC AGCTCT CGCTCG



DNA

ACTGC ACCTAT CGTTCG

ACTGC ACCTAT CGTTCG

ACCCC AGCTCT CGCTCG

Taxa Characters! B1 ACTGCACCTATCGTTCG! B2 ACTCCACCTATCGTTCG! E1 ACTCCAGCTATCGATCG! E2 ACTCCAGGTATCGATCG! A1 ACCCCAGCTCTCGCTCG! A2 ACCCCAGCTCTGGCTCG! New1 ACCCCAGCTCTGCCTCG! New2 ACTGCACCTATCGTTCG



DNA

ACTGC ACCTAT CGTTCG

ACTGC ACCTAT CGTTCG

ACCCC AGCTCT CGCTCG





DNA

ACTGC ACCTAT CGTTCG

ACTGC ACCTAT CGTTCG

ACCCC AGCTCT CGCTCG




One can estimate cell counts from the number of times each sequence is seen.


DNA

Taxa Characters! B1 ACTGCACCTATCGTTCG! B2 ACTCCACCTATCGTTCG! E1 ACTCCAGCTATCGATCG! E2 ACTCCAGGTATCGATCG! A1 ACCCCAGCTCTCGCTCG! A2 ACCCCAGCTCTGGCTCG! New1 ACCCCAGCTCTGCCTCG! New2 AGGGGAGCTCTGCCTCG! New3 ACTCCAGCTATCGATCG! New4 ACTGCACCTATCGTTCG



ACTGC ACCTAT CGTTCG

ACTCC AGCTAT CGATCG

ACCCC AGCTCT CGCTCG

AGGGG AGCTCT CGCTCG

AGGGG AGCTCT CGCTCG

ACTGC ACCTAT CGTTCG


DNA

Taxa Characters! B1 ACTGCACCTATCGTTCG! B2 ACTCCACCTATCGTTCG! E1 ACTCCAGCTATCGATCG! E2 ACTCCAGGTATCGATCG! A1 ACCCCAGCTCTCGCTCG! A2 ACCCCAGCTCTGGCTCG! New1 ACCCCAGCTCTGCCTCG! New2 AGGGGAGCTCTGCCTCG! New3 ACTCCAGCTATCGATCG! New4 ACTGCACCTATCGTTCG



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! B1 ACTGCACCTATCGTTCG! B2 ACTCCACCTATCGTTCG! E1 ACTCCAGCTATCGATCG! E2 ACTCCAGGTATCGATCG! A1 ACCCCAGCTCTCGCTCG! A2 ACCCCAGCTCTGGCTCG! New1 ACCCCAGCTCTGCCTCG! New2 ACGGCAGCTCTGCCTCG




DNA DNADNA

ACTGC ACCTAT CGTTCG

ACTCC AGCTAT CGATCG

ACCCC AGCTCT CGCTCG

Taxa Characters! B1 ACTGCACCTATCGTTCG! B2 ACTCCACCTATCGTTCG! E1 ACTCCAGCTATCGATCG! E2 ACTCCAGGTATCGATCG! A1 ACCCCAGCTCTCGCTCG! A2 ACCCCAGCTCTGGCTCG! New1 ACCCCAGCTCTGCCTCG! New2 ACGGCAGCTCTGCCTCG



Can compare many samples too

rRNA PCR

• General workflow ! rRNA PCR ! Sequence ! Cluster sequences into groups (known as operational

taxonomic units or OTUs) ! Measure relative abundance of OTU by # of

sequences in that group ! Try and assign a taxonomy to each OTU

!

• Caveats ! Copy number varies extensively ! Not all organisms amplified

!28


Key Finding 1: Major phyla of bacteria and archaea (as of 2002)

No cultures

Some cultures29


Key Finding #2: Biogeography

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Key Finding #3: Microbiomes

Censored

Censored

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Surpassing Moore Law (ADDED SLIDE)

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• Ecology

• Evolution


• Who are We?

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The Human Microbiome

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The Microbiome

“The Nobel laureate Joshua Lederberg has suggested using the term "microbiome" to describe the collective genome of our indigenous microbes (microflora), the idea being that a comprehensive genetic view of Homo sapiens as a life-form should include the genes in our microbiome”

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Lora Hooper and Jeff Gordon (Commensal Host-Bacterial Relationships in the Gut Science 11 May 2001: Vol. 292. no. 5519, pp. 1115 - 1118


The Rise of the Microbiome

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0

350

700

1050

1400

00 01 02 03 04 05 06 07 08 09 10 11 12

Pubmed “Microbiome” Hits

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• We are covered in a cloud of microbes

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• We are covered in a cloud of microbes !

• This “microbiome” likely is involved in many important human phenotypes

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• This “microbiome” LIKELY is involved in many important human phenotypes

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• This “microbiome” LIKELY is INVOLVED in many important human phenotypes

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!42

Turnbaugh et al Nature. 2006 444(7122):1027-31.


http://www.ncbi.nlm.nih.gov/pubmed/17183312#

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Lesson 1 !

Think Like and Ecologist


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Ecology of the Microbiome 1: !

Biogeography


Biogeography

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Censored

Censored

Human biogeography

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Skin Biogeography

• w

47Julie Segre, NHGRI


CSI Microbiology (well, CSI Miami but good enough ...)

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!49

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Population Biology and Variability


Variability Across People

50Huttenhower et al. 2012.


Variability is Correlated to Many Health States

• Microbial community different in many disease states compared to healthy individuals

• Unclear if this is cause or effect in most cases

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Variation Between Countries (ADDED SLIDE)

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The ISME Journal (2013) 7, 85–95; doi:10.1038/ismej.2012.81MJ Blaser et al. ISMEJ 2012 US Amerindian

Actinobacteria (Propionibacteria)

Firmicutes (Staphylococcus)

Rela

tive

abun

danc

e Actinobacteria dominates in the US

Boulder NY Platanillal A Platanillal B

Proteobacteria


Taxa Enrichment in Disease - IBD (ADDED SLIDE)

• http://genomebiology.com/2012/13/9/R79/figure/F

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Morgan et al. Genome Biology 2012, 13:R79

http://genomebiology.com/2012/13/9/R79/figure/F

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Community Assembly


Colonization Before, During and After Birth

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Mom Knows Best: The Universality of Maternal Microbial Transmission!Lisa J. Funkhouser Seth R Bordenstein


Milk and Infant Microbiome

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Colonization Throughout Life

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The Kitten Microbiome

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!59

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Disturbance


Disturbing the Microbiome

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!61

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Restoration


Restoring the Microbiome: Probiotics and Prebiotics

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Intestinal Transplant

63Hartman et al. PNAS 2009


Microbiome Transplant

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Coprophagia

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Transfaunation

66


Fecal “transplants”

67


Openbiome

68


DIY Fecal Transplant

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DIY Fecal Transplant