Talk by Jonathan Eisen for GSAC2000 on "Phylogenomics"

Ad

Ad

Ad

Ad

Ad

Ad

Ad

Ad

Ad

Ad

Ad

Ad

TIGRTIGR
Phylogenomics:
Combining Evolutionary
Reconstructions and Genome
Analysis into a Single
Composite Approach
0
2500...

TIGRTIGR
Wolbachia Genome Project
• Information is available through TIGRs
unfinished genomes service (go to
www.tigr.org ...

TIGRTIGR

TIGRTIGR
Topics of Discussion
• Introduction to phylogenomics
• Phylogenomics Examples
– Functional prediction
– Gene dupl...

TIGRTIGRTIGRTIGR
“Nothing in biology makes sense
except in the light of evolution.”
T. H. Dobzhansky (1973)

TIGRTIGR

TIGRTIGR
Uses of Evolutionary Analysis in
Molecular Biology
• Identification of mutation patterns (e.g., ts/tv ratio)
• Am...

TIGRTIGR
Evolutionary Studies Improve
Most Aspects of Genome Analysis
• Phylogeny of species places comparative data in pe...

TIGRTIGR
Genome Information and Analysis
Improves Studies of Evolution
• Complete genome information particularly useful
•...

TIGRTIGR
Phylogenomic Analysis
• There are feedback loop between evolutionary and
genome analysis such that for many studi...

TIGRTIGR
Outline of Phylogenomics
Gene Evolution Events
Phenotype Predictions
Database
Species tree Presence/AbsenceGene t...

TIGRTIGR

TIGRTIGR
Uses of Phylogenomics I:
Functional Predictions

TIGRTIGR
MutS.Aquae orf.Trepa
SPE1.Drome
MSH2.Xenla
MSH2.Rat
MSH2.Mouse
MSH2.Human
MSH2.Yeast
MSH2.Neucr
atMSH2.Arath
MutS...

TIGRTIGR
4 F17L22 170 Arabidopsis thali
4455279 Arabidopsis thaliana
1049068 Lycopersicon esculentu
Homo sapiens
5514652 D...

TIGRTIGR
Novel Large Subunit Rubisco in
Chlorobium tepidumAgathis.gi3982533
Agathis.gi3982549
Araucaria.gi3982517
Agathis....

TIGRTIGR
Evolutionary Analysis Improves
Functional Prediction
• Many examples of using phylogenetic trees
– DNA repair - E...

TIGRTIGR
Uses of Phylogenomics II:
Gene Duplication

TIGRTIGR
Why Duplications Are Useful to Identify
• Allows division into orthologs and paralogs
• Aids functional predictio...

TIGRTIGR
Expansion of MCP Family in V. cholerae
E.coligi1787690
B.subtilisgi2633766
Synechocystissp. gi1001299
Synechocyst...

TIGRTIGR
ArsA Duplications in C. tepidum
Chlvi.497325
CHLTE ORF02621
CHLTE ORF00955
CHLTE ORF03444
SYNSP 1001709
CHLTE ORF...

TIGRTIGR
Levels of Paralogy Within A Genome

TIGRTIGR
C. pneumoniae Paralogs - All
0
250000
500000
750000
1000000
1250000
SubjectOrfPosition
0 250000 500000 750000 100...

TIGRTIGR
C. pneumoniae Paralogs - Top
0
250000
500000
750000
1000000
1250000
SubjectOrfPosition
0 250000 500000 750000 100...

TIGRTIGR
C. pneumoniae Paralogs – Recent
0
250000
500000
750000
1000000
1250000
SubjectOrfPosition
0 250000 500000 750000 ...

TIGRTIGR
Uses of Phylogenomics III:
Genetic Exchange within Genomes

TIGRTIGR

TIGRTIGR
Uses of Phylogenomics IV:
Gene Loss

TIGRTIGR
Why Gene Loss is Useful to Identify
• Indicates that gene is not absolutely required for
survival
• Correlated lo...

TIGRTIGR
EuksArch Bacteria
Loss
Evolutionary O rigin of Gene
MT MJ SC HS AA DR TA BS MG MP BB TP HP HI EC SS MT
Presence (...

TIGRTIGR
5
1
2
3
4
E.coli
H.influenzae
N.gonorrhoeae
H.pylori
Syn.sp
B.subtilis
S.pyogenes
M.pneumoniae
M.genitalium
A.aeo...

TIGRTIGR
Need for Phylogenomics Example:
Gene Duplication and Loss
• Genome analysis required to determine number of
homol...

TIGRTIGR
Uses of Phylogenomics V:
Comparison of Closely Related
Genomes

TIGRTIGR
V. cholerae vs. E. coli All Hits
0
1000000
2000000
3000000
4000000
5000000E.coliCoordinates
0 1000000 2000000 300...

TIGRTIGR
V. cholerae vs. E. coli Top Hits
0
1000000
2000000
3000000
4000000
5000000
E.coliCoordinates
0 1000000 2000000 30...

TIGRTIGR
V. cholerae vs. E. coli
Only if EC-Orf is Closest in All Genomes
0
1000000
2000000
3000000
4000000
5000000
E.coli...

TIGRTIGR
V. cholerae vs. E. coli F+R
0
1000000
2000000
3000000
4000000
5000000
Bert
Ecoli R
Ecoli

TIGRTIGR
Uses of Phylogenomics VI:
Evolution Within Species

TIGRTIGR
Musser-Type Evolution (Combined
Phylogeny)

TIGRTIGR
Consistency Indices (Combined Phylogeny)
Calculated over stored trees
CI
0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
...

TIGRTIGR
Uses of Phylogenomics VII:
Horizontal Gene Transfer and
Species Evolution

TIGRTIGR
Vertical Inheritance
from Doolittle, 1999

TIGRTIGR
Horizontal Gene Transfer
from Doolittle, 1999

TIGRTIGR
Why Gene Transfers Are Useful to Identify
• Laterally transferred genes frequently involved in
environmental adap...

TIGRTIGR
Horizontal Gene Transfer I
from Doolittle, 1999

TIGRTIGR
0
100
200
300
400
500
600
700
500 1000 1500 2000 2500 3000 3500 4000 4500
Orfs in Target Genome
Best
Matches
Best...

TIGRTIGR
Best Matches Per ORF
0
0.05
0.1
0.15
0.2
0.25
0.3
BM/Orfs
CHLTE
PORGI
BACSU
MCYTU
BBUR
TREPA
CHLPN
ECOLI
NEIME
RI...

TIGRTIGR
Possible Plastid ORFs
• So far, over 900 ORFs are candidates for being
derived from the plastid genome some time ...

TIGRTIGR
Organellar HSP60s
DROMECG12101
DROMECG7235
DROMECG2830
DROMECG16954
ARATH At2g33210
ARATH F14O13.19
ARATH MCP4.7
...

TIGRTIGR
Evolutionary Genome Scanning
• Distribution patterns/phylogenetic profiles
• Patterns of evolution (ds/dn, correl...

TIGRTIGR
Evolutionary Diversity Still Poorly
Represented in Complete Genomes
Tmf-penden
R-rubrum3
Azs-brasi2
Rm-vanniel
Rh...

TIGRTIGR
Acknowledgements
• Genome duplications: S. Salzberg, J. Heidelberg, O.
White, A. Stoltzfus, J. Peterson
• Genome ...

TIGRTIGR
True Phylogenetic Methods
Work Best
MutS2.Syns
MutS2.Bacs
MutS2.Help
MutS2.Deir
Mutsl.Mett
MSH4.Celeg
MSH4.Yeast
...

TIGRTIGR
Reconciling a Tree of Life in the
Context of Lateral Gene Transfer

TIGRTIGR
Whole Genome Phylogeny
Huynen, Snel & Bork, 1999

TIGRTIGR
rRNA vs. Whole Genome Trees
Mycobacterium tuberculosis
Bacillus subtilis
Synechocystis sp.
Caenorhabditis elegans...

TIGRTIGR
Serratia marcescens
Proteus mirabilis
Proteus vulgaris
Escherichia coli
Erwinia carotovora
Yersinia pestis
Entero...

TIGRTIGR
TIGTIG
RR
OtherOther
peoplepeople
Mom and DadMom and Dad
S. KarlinS. Karlin
M. FeldmanM. Feldman
A. M. CampbellA....

TIGRTIGR
Figure 4. Best matches by role
categoryHits By Role Category
0.00
0.10
0.20
0.30
0.40
0.50
0.60
0.70
0.80
Role Ca...

TIGRTIGR
Uses of Phylogenomics VII:
Specialization

TIGRTIGR
Species Distribution of Homologs of
D. radiodurans Genes
0
10
20
30
40
50
60
0 5 10 15 20
0
50
100
150
0 5 10 15 ...

TIGRTIGR
Megaplasmid I:
Iron Utilization/Iron Transport
ORFB040 Na+/H+ antiporterORFB040 Na+/H+ antiporter
ORFB042 iron AB...

TIGRTIGR
Carboxydothermus
hydrogenoformans
• Isolated in Yellowstone
• Thermophile (grows at 80°C)
• Anaerobic
• Grows on ...

TIGRTIGR
Wolbachia sp.
• Endosymbionts of many invertebrates
• We are sequencing the symbiont of the fruit
fly and a paras...

TIGRTIGR
Methylococcus capsulatus
• Member of the γ-Proteobacteria
• Grows on methane
• Collaboration with University of B...

TIGRTIGR
Figure 6. Citrate lyase domains
Human Citrate lyase
CelegCitrate lyase
Cyanophora
A. thaliana F5E6.2 chrIII
Chlor...

TIGRTIGR
Chlorobium tepidum Strain TLS
C. tepidum mat in highly sulfidic
“Travelodge Stream”,
Rotorua, New Zealand
(from C...

TIGRTIGR
N
N N
N
O
H 3 C
H 3 C
C HOH
C H 3
H 3C
O
O
M g
C H 3
C H 2 C H 2C H 3
C H 2 C H 3
H
H
C H 3
or
C H 2 C H(CH3 )2
C...

TIGRTIGR
Protein Duplications
• Of 14,881 ORFs with matches to a
complete genome, 13,092 have a best match
to another A. t...

TIGRTIGR
Best Matches to Complete Genomes
0
1000
2000
3000
4000
BestMatches
CHLTE
PORGI
BACSU
MCYTU
BBUR
TREPA
CHLPN
ECOLI...

TIGRTIGR
Best Matchers/ORF -
Prokaryotes
0
0.05
0.1
0.15
0.2
BM/Orfs
CHLTE
PORGI
BACSU
MCYTU
BBUR
TREPA
CHLPN
ECOLI
NEIME
...

TIGRTIGR
U28187 Nasonia longicornis IV7
U28188 Nasonia vitripennis LbII
U28182 Nasonia giraulti RV2 A
U28203 Nasonia girau...

TIGRTIGR
Uses of Phylogenomics II:
Knowing when to Not Predict
Functions

TIGRTIGR

TIGRTIGR
Evolution of Uracil Glycosylase
• Ung activity has evolve many times (many non-
homologous proteins have uracil-D...

TIGRTIGR
Evolution of Photoreactivation
• All known enzymes that perform photoreactivation are part of
a single large phot...

TIGRTIGR
Evolution of Alkyltransferases
• All known alkyltransferases share a conserved,
homologous alkyltransferase domai...

TIGRTIGR
Examples of Horizontal Transfers
• Antibiotic resistance genes on plasmids
• Insertion sequences
• Pathogenicity ...

TIGRTIGR
Archaeal genes in bacterial genomesArchaeal genes in bacterial genomes**
Bacterial speciesBacterial species Best ...

TIGRTIGR
• Possibilitiy of gene transfer criticized
because of possibility of shared descent
• C. tepidum – green sulfur b...

Share SlideShare

Facebook
Twitter
LinkedIn

Embed

Size (px)

Show related SlideShares at end

WordPress Shortcode

Link

LinkedIn
Facebook
Twitter
Email

Replay

Top clipped slide

1 of 80 Ad

1 of 80 Ad