More Questions Than Answers - NIH VideoCastThermotogae TM6 OS-K Termite Group OP8 Marine GroupA WS3...
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TIGR TIGR TIGR More Questions Than Answers: Comparative genomics, evolutionary analysis, and knowing what we do not know about DNA repair. Jonathan A. Eisen September 20, 2005
Transcript of More Questions Than Answers - NIH VideoCastThermotogae TM6 OS-K Termite Group OP8 Marine GroupA WS3...
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More Questions Than Answers:
Comparative genomics, evolutionaryanalysis, and knowing what we do not
know about DNA repair.
Jonathan A. EisenSeptember 20, 2005
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More Questions Outline• Background• More questions
– I. Case study - H. pylori– II. New subfamilies and domain patterns– III. Recent duplications– IV. Missing pathways– V. Unusual patterns– VI. Even more questions
• Answers– Better informatics– Experiments
• The end
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Background
Genome sequencing andevolutionary analysis
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Fleischmann et al.1995
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Prokaryotic Genomes
From C. M. Fraser
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Why Completeness is Important
• Improves characterization of genome features• Better comparative genomics• Presence/absence is less subjective• Missing sequence might be important (e.g.,
centromere)• Allows researchers to focus on biology not
sequencing• Facilitates large scale correlation studies• Controls for contamination
see Fraser et al. (2002). J. Bacteriol. 184: 6403-5
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Analysis of Complete Genomes
• Identification/prediction of genes• Characterization of gene features• Characterization of genome features• Prediction of gene function• Prediction of pathways• Integration with known biological data• Comparative genomics
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“Nothing in biology makes senseexcept in the light of evolution.”
T. H. Dobzhansky (1973)
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Evolutionary Perspective andComparative Biology
• Comparative biology is the analysis of differencesand similarities between species.
• An evolutionary perspective is useful in such studiesbecause this allows one to focus not just on thelevels and degrees of similarity or difference but onhow and why similarities and differences came tobe.
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More Questions I:A Case Study
The Unbearable Lightness ofHelicobacter pylori’s
DNA Repair Gene List
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TIGRTIGRTIGR Tomb et al. 1997
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H. pylori and MutS
• H. pylori has a MutS-like gene but not MutL
• Prior to this genome, all species that encoded aMutS homolog also encoded a MutL homolog
• Experimental studies have shown MutS and MutLalways work together in mismatch repair
• Problem: what do we conclude about H. pylorimismatch repair
See Eisen et al, 1997
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Two Prokaryotic MutS Subfamilies
5
1
2
34
*
E. coli
H. influenzae
N. gonorrhoaea
H. pylori
Syn. sp
B. subtilis
S. pyogenes
M. pneumoniae
M. genitalium
A. aeolicus
D. radiodurans
T.pallidum
B.burgdorferi
Syn. sp
B. subtilis
S. pyogenes
A. aeolicus
D. radiodurans
B. burgdorferi
MutS1MutS-I lineageMutS-II lineage
Species TreeGene loss
* Gene Duplications1-5 Gene Loss
A. B.
A. aeolicus
S pyogenes
B. subtilis
Syn. sp
D. radiodurans
MutS2
B.burgdorferi
Eisen, 1998, NAR 26: 4291-4300.
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H. pylori No MMR
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PHYLOGENENETIC PREDICTION OF GENE FUNCTION
IDENTIFY HOMOLOGS
OVERLAY KNOWNFUNCTIONS ONTO TREE
INFER LIKELY FUNCTIONOF GENE(S) OF INTEREST
1 2 3 4 5 6
3 5
3
1A 2A 3A 1B 2B 3B
2A 1B
1A3A
1B 2B3B
ALIGN SEQUENCES
CALCULATE GENE TREE
12 4
6
CHOOSE GENE(S) OF INTEREST
2A
2A
53
Species 3Species 1 Species 2
1
1 2
2
2 31
1A 3A
1A 2A 3A
1A 2A 3A
4 6
4 5 6
4 5 6
2B 3B
1B 2B 3B
1B 2B 3B
ACTUAL EVOLUTION(ASSUMED TO BE UNKNOWN)
Duplication?
EXAMPLE A EXAMPLE B
Duplication?
Duplication?
Duplication
5
METHOD
Ambiguous
Eisen, 1998, GenomeRes. 8: 163-167.
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More Questions II:
Long Lost Cousins
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Two UvrA Subfamilies• Some specieshave a secondUvrA-like gene
• Some results onUvrA2 in D.radiodurans
• Unclear whatUvrA2s do
Eisen and Wu, 2002, Theor. Pop. Biol. 61: 481-487.
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UvrA2UvrA2 S. coelicolor
DrrC S. peuceteus
UvrA2 D. radiodurans
Duplicationin UvrAfamily
UvrA1
UvrA H. influenzae
UvrA E. coli
UvrA N. gonorrhoaea
UvrA R. prowazekii
UvrA S. mutans
UvrA S. pyogenes
UvrA S. pneumoniae
UvrA B. subtilis
UvrA M. luteus
UvrA M. tuberculosis
UvrA M. hermoautotrophicum
UvrA H. pylori
UvrA C. jejuni
UvrA P. gingivalis
UvrA C. tepidum
uvra1 D. radiodurans
UvrA T. thermophilus
UvrA T. pallidum
UvrA B. burgdorefi
UvrA T. maritima
UvrA A. aeolicus
UvrA Synechocystis sp.
UvrA1
UvrA2
OppDFUUP
NodILivF
XylG
NrtDC
PstB
MDR
HlyB
TAP1
CFTR, SUR
A. ABC Transporters B. UvrA Subfamily
Evolution of UvrA Family
TIGRTIGRTIGRVan Houten et al, 2002,PNAS 99: 2581-2583.
UvrC vs. Cho• Cho in E. coli isinvolved in analternative NERpathway (seeMoolenar et al.2002)
• What do theother relatives ofCho do?
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Phr.S thypPHR E. coli
ORFA00965phr.neucr
Phr.TrichoPhr.Yeast
Phr.B firmphr.strpy
phr.halobaPHR STRGR
pCRY1.humaphr.mouse
phr2.humanphr2.mouse
phr.drosopphr3.Synsp ORF02295.Vibch
phr.neigoORF01792.Vibch
Phr.AdiantPhr2.AdianPhr3.Adianphr.tomatoCRY1 ARATH
phr.phycomCRY2 ARATHPHH1.arath
PHR1 SINALphr.chlamy
PHR ANANIphr.Synsp
PHR SYNY3 phr.Theth
Rh.caps
MTHF typeCPDPhotolyases
6-4Photolyases
BlueLightReceptors
8-HDF typePhotolyase
Three V. cholerae Phr Homologs
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AlkA Domain (O6-Me-G glycosylase)Ogt Domain (O6-Me-G alkyltransferase)Ada Domain (transcriptions regulator)
Ada E. coliAda H. inflOgt E. coliOgt H. inflOgt Gram+Ogt D. radio
AlkA Gram+AlkA E. coli
MGMT Euks
Eisen and Hanawalt, 1999, Mut. Res. 435: 171-213.
Alkylation Repair Genes
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More Questions III:
Does 1+1 = 1? Or 2?
TIGRTIGRTIGR Wu et al, 2004, PLOS Biology 2: 327-341
Wolbachia pipientis wMel
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MutL Duplication in Wolbachia
Eisen, unpublished.
TIGRTIGRTIGRWood et al., 2001, Science294: 2317-2323
Agrobacterium tumefaciens
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Chromosome1 DnaE, LigA, XthChromosome2 DnaE, LigAPlasmid1 DnaE, LigA, XthPlasmid2 DnaE?, LigA
Wood et al., 2001, Science 294: 2317-2323
Agrobacterium tumefaciens hasmultiple duplications
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Schizosaccharomyces pombeNeurospora crassaClostridium perfringensBacillus subtilisBacillus cereusBacillus anthracis UVDE2Bacillus haloduransBacillus anthracis UVDE1Deinococcus radioduransNostoc sp. PCC 7120
Duplication of UVDE in Anthrax
Eisen,unpublished.
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More Questions IV:
When a good repair pathwayis hard to find
• P. falciparum initialannotation showed thepresence of a DNA LigaseIV homolog but not a DNALigase I.
• Yet Ligase I has more of acore function in othereukaryotes, while Ligase IVis involved in NHEJ
P. falciparum DNA Repair
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Arabidopsis thalianaGP9651815gDrosophila melanogasterGP72929
Homo sapiensSPP49917DNL4 HUMANGallus gallusGP15778121dbjBAB6Xenopus laevisGP18029886gbAAL5
Candida albicansSPP52496DNLI CSaccharomyces cerevisiaeGP1151Schizosaccharomyces pombeGP700
Camelpox virusGP18483081gbAAL7Variola major virusGP439074gbA
Cowpox virusGP20153167gbAAM136Vaccinia virusGP2772802gbAAB96VIRUS vaccinia 9791118refNP 06Vaccinia virus strain Tian TanMonkeypox virusGP17529940gbAAL
Homo sapiensSPP49916DNL3 HUMANMus musculusGP1794221gbAAC5300
Xenopus laevisGP18029884gbAAL5lumpy skin disease virusGP1514
Swinepox virusGP18448623gbAAL6Myxoma virusGP6523988gbAAF1502Rabbit fibroma virusGP392838gb
Fowlpox virusGP453602embCAA828Drosophila melanogasterGP72996
Arabidopsis thalianaSPQ42572DNOryza sativaGP16905197gbAAL310
Crithidia fasciculataGP312384eCaenorhabditis elegansSPQ27474
Drosophila melanogasterGP72916Homo sapiensSPP18858DNL1 HUMANMus musculusSPP37913DNL1 MOUSERattus norvecusSPQ9JHY8DNL1 RAXenopus laevisSPP51892DNL1 XEN
Plasmodium falciparumGP1815859Schizosaccharomyces pombeSPP12Saccharomyces cerevisiaeSPP048
Aeropyrum pernixSPQ9YD18DNLI AAcidianus ambivalensSPQ02093DNSulfolobus solfataricusSPQ980TSulfolobus shibataeSPQ9P9K9DNLSulfolobus tokodaiiSPQ976G4DNLAquifex aeolicusGP2983805gbAACAquifex aeolicusSPO67398DNLI APyrobaculum aerophilumGP409906
uncultured crenarchaeote 74A4GThermoplasma acidophilumSPQ9HJThermoplasma volcaniumOMNINTL0
Methanosarcina acetivorans strArchaeoglobus fuldusSPO29632DN
A METAC 19916535gbAAM05952.1 DPyrococcus abyssiSPQ9V185DNLI Pyrococcus horikoshiiSPO59288DPyrococcus furiosusSPP56709DNLThermococcus kodakaraensisGP10Thermococcus fumicolansSPQ9HH0Methanopyrus kandleri AV19GP19
Methanococcus jannaschiiSPQ576Halobacterium sp.SPQ9HR35DNLI
Streptomyces coelicolorSPQ9FCBLymantria dispar nucleopolyhed
Ligase IV
Viral Ligases
Ligase I
Archaeal Ligases
DNA Ligase Tree
Eisen, unpublished
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Arabidopsis thaliana
Drosophila melanogaster
Homo sapiens
Gallus gallus
Xenopus laevis
Candida albicans
Saccharomyces cerevisiae
Schizosaccharomyces pombe
DNA Ligase IV SubTree
Eisen, unpublished
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Arabidopsis thalianaOryza sativaCrithidia fasciculataCaenorhabditis elegansDrosophila melanogasterHomo sapiensMus musculusRattus norvecusXenopus laevisPlasmodium falciparumSchizosaccharomyces pombeSaccharomyces cerevisiae
DNA Ligase I SubTree
Eisen, unpublished
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No NHEJ in P. falciparum?
• No Ligase IV
• None of the other “normal” NHEJ genes foreukaryotes
• Does it use only homologous recombinationor is there another NHEJ pathway?
See Gardner et al 2002
TIGRTIGRTIGR Wu et al, 2004, PLOS Biology 2: 327-341
Wolbachia pipientis wMel
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Wuet al.,2004
Wolbachia Evolves Rapidly
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Insect Symbiont Tree
Wu et al. In preparation
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Intracellular Organisms andEvolutionary Rate
• Many intracellular bacteria have higherevolutionary rates than free-living relatives
• Two main theories to explain this:– loss of DNA repair– altered population genetics (e.g., bottlenecks)
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Repair Category Gene Name
MMR mutS1, mutL1, mutL2NER uvrABCDBER fpg, mpg, nthAP Endo xthRec recA, ruvABC, recG,
recFJROther ligA, ssb, radA
Wolbachia Has Similar Repair Genesto More Slowly Evolving Species
Wu et al., 2004
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Insect Symbiont RepairBuchnera(APS)
Buchnera(BP)
Buchnera(SG)
Wigglesworthia Blochmannia Baumannia
Base Excision RepairUng gi15616802 gi27904674 - gi32491032 gi33519990 GEBCORF00107MutY gi15617145 gi27904974 gi21672797 - gi33519714 -Fpg - - - - - GEBCORF00321Nfo gi15616757 gi27904631 gi21672420 - - GEBCORF00528Xth - - - gi32491120 gi33519889 -
Nucleotide Excision RepairUvrD - - - gi32491021 - GEBCORF00274
Transcription-Repair Coupling FactorMfd gi15616905 gi27904769 - gi32490848 - -
Mismatch RepairMutL gi15617161 gi27904987 gi21672810 - - GEBCORF00079MutS gi15617028 gi27904861 gi21672681 - - GEBCORF00349MutH - gi27904531 - - - GEBCORF00038
8-oxo-dGTP HydrolysisMutT gi15616821 - gi21672482 - - -
Pyrimidine Dimer RepairPhr gi15616910 gi27904772 - gi32490931 - -
Homologous RecombinationRecG - - - - - GEBCORF00259RuvA - - - - - GEBCORF00452RuvB - - - - - GEBCORF00451RuvC - - - gi32490863 - GEBCORF00453RecB gi15617053 gi27904885 gi21672704 gi32491015 gi33519733 GEBCORF00043RecC gi15617052 gi27904884 gi21672703 gi32491014 gi33519731 GEBCORF00042RecD gi15617054 gi27904886 gi21672705 gi32491016 gi33519732 GEBCORF00044RecA - - - gi32490984 - GEBCORF00346RecJ - - - gi32491188 - GEBCORF00298RmuC - - - - gi33520059 GEBCORF00163
Wu et al. In preparation
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Insect Nutritional Symbiont Tree
++++-+-+--+-
RecAMutLS
Wu et al. In preparation
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Organelle Derived Genes in theA. thaliana Nuclear Genome
Pathway GenesMismatch Repair MutS2Base Excision Repair Fpg, Tag?Nucleotide ExcisionRepair
Mfd
Recombination RecA, RecGDirect Repair PhrOther Lon
Eisen and Britt, 2000
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More Questions V:
One of these things just doesnot belong here
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Other Unusual Patterns
• RecBCD but no RecA• Mfd but no UvrABCD• No Ung in thermophiles• Rad25 in some bacteria• No MSH4, 5 in many eukaryotes• No CSB in some eukaryotes• Tons of repair genes in Mimivirus
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Archaea
• NER– UvrABC in some– Rad1, Rad2, Rad25 etc in others– Some species with both
• MMR– Many species with MutS2 only– Some with multiple MutLs, MutS1s– Three MutSs in Halophiles
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Even More Questions?
You ain’t seen nothing yet
TIGRTIGRTIGRHugenholtz 2002
Biased Sampling of Genomes
• Most bacterial genomescome from three phyla
• Most phyla have nogenome sequences
• Even worse samplingfor eukaryotes andarchaea
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Acidobacteria
Bacteroides
Fibrobacteres
Gemmimonas
Verrucomicrobia
Planctomycetes
Chloroflexi
Proteobacteria
Chlorobi
FirmicutesFusobacteria Actinobacteria
Cyanobacteria
Chlamydia
Spriochaetes
Deinococcus-Thermus Aquificae
Thermotogae
TM6OS-K
Termite GroupOP8
Marine GroupAWS3
OP9
NKB19
OP3
OP10
TM7
OP1OP11
Nitrospira
SynergistesDeferribacteres
Thermudesulfobacteria
Chrysiogenetes
Thermomicrobia
Dictyoglomus
Coprothmermobacter
• At least 40phyla ofbacteria
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Acidobacteria
Bacteroides
Fibrobacteres
Gemmimonas
Verrucomicrobia
Planctomycetes
Chloroflexi
Proteobacteria
Chlorobi
FirmicutesFusobacteria Actinobacteria
Cyanobacteria
Chlamydia
Spriochaetes
Deinococcus-Thermus Aquificae
Thermotogae
TM6OS-K
Termite GroupOP8
Marine GroupAWS3
OP9
NKB19
OP3
OP10
TM7
OP1OP11
Nitrospira
SynergistesDeferribacteres
Thermudesulfobacteria
Chrysiogenetes
Thermomicrobia
Dictyoglomus
Coprothmermobacter
• At least 40phyla ofbacteria
• Genomesequences aremostly fromthree phyla
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Acidobacteria
Bacteroides
Fibrobacteres
Gemmimonas
Verrucomicrobia
Planctomycetes
Chloroflexi
Proteobacteria
Chlorobi
FirmicutesFusobacteria Actinobacteria
Cyanobacteria
Chlamydia
Spriochaetes
Deinococcus-Thermus Aquificae
Thermotogae
TM6OS-K
Termite GroupOP8
Marine GroupAWS3
OP9
NKB19
OP3
OP10
TM7
OP1OP11
Nitrospira
SynergistesDeferribacteres
Thermudesulfobacteria
Chrysiogenetes
Thermomicrobia
Dictyoglomus
Coprothmermobacter
• At least 40phyla ofbacteria
• Genomesequences aremostly fromthree phyla
• Some otherphyla areonly sparselysampled
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Acidobacteria
Bacteroides
Fibrobacteres
Gemmimonas
Verrucomicrobia
Planctomycetes
Chloroflexi
Proteobacteria
Chlorobi
FirmicutesFusobacteria Actinobacteria
Cyanobacteria
Chlamydia
Spriochaetes
Deinococcus-Thermus Aquificae
Thermotogae
TM6OS-K
Termite GroupOP8
Marine GroupAWS3
OP9
NKB19
OP3
OP10
TM7
OP1OP11
Nitrospira
SynergistesDeferribacteres
Thermudesulfobacteria
Chrysiogenetes
Thermomicrobia
Dictyoglomus
Coprothmermobacter
• At least 40phyla ofbacteria
• Genomesequences aremostly fromthree phyla
• Some otherphyla areonly sparselysampled
• Solution:sequencemore phyla
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Solution II:Environmental Sequencing
shotgunshotgun
sequencesequence
Warner Brothers, Inc.Warner Brothers, Inc.
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Schizosaccharomyces pombeNeurospora crassaClostridium perfringensBacillus subtilisBacillus cereusBacillus anthracis UVDE2Bacillus haloduransBacillus anthracis UVDE1Deinococcus radioduransNostoc sp. PCC 7120
Duplication and Loss of UVDE
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0.1
Eisen, unpublished
TIGRTIGRTIGRBacteriophage_Aeh1_gi38640041-
B_halodurans_gi15615160-NC_002B_cereus_ATCC_14579_gi30018497B_cereus_ATCC_10987_gi42779349B_cereus_ZK_gi52144992-NC_0062B_anthracisSterne_gi49183267-NB_anthracis''_gi47525505-NC_00B_anthracisAmes_gi30260424-NC_B_thuringiensi_gi49481707-NC_0
B_cereus_ATCC_14579_gi30023378B_cereus_ATCC_10987_gi42784523B_cereus_ZK_gi52140215-NC_0062B_thuringiensi_gi49481769-NC_0B_anthracis''_gi47530914-NC_00B_anthracisAmes_gi30265371-NC_B_anthracisSterne_gi49188182-N
Clostridium_perfringens_SM101Clostridium_perfringens13_gi18Thermus_thermophilus_HB27_gi46
Schizosaccharomyces_pombe_gi19Cryptococcus_neoformans_var._n
Mimivirus_gi55819554-NC_006450
Desulfotalea_psychrophila_LSv5
Parachlamydia_sp._UWE25_gi4644Deinococcus_radiodurans_gi1580
Nostoc_sp._PCC_7120_gi17228758
Haloarcula_marismortui_ATCC_43
0.1
Eisen, unpublished
TIGRTIGRTIGRBacteriophage_Aeh1_gi38640041-
B_halodurans_gi15615160-NC_002B_cereus_ATCC_14579_gi30018497B_cereus_ATCC_10987_gi42779349B_cereus_ZK_gi52144992-NC_0062B_anthracisSterne_gi49183267-NB_anthracis''_gi47525505-NC_00B_anthracisAmes_gi30260424-NC_B_thuringiensi_gi49481707-NC_0
B_cereus_ATCC_14579_gi30023378B_cereus_ATCC_10987_gi42784523B_cereus_ZK_gi52140215-NC_0062B_thuringiensi_gi49481769-NC_0B_anthracis''_gi47530914-NC_00B_anthracisAmes_gi30265371-NC_B_anthracisSterne_gi49188182-N
Clostridium_perfringens_SM101Clostridium_perfringens13_gi18Thermus_thermophilus_HB27_gi46
Schizosaccharomyces_pombe_gi19Cryptococcus_neoformans_var._n
Mimivirus_gi55819554-NC_006450
Desulfotalea_psychrophila_LSv5
Parachlamydia_sp._UWE25_gi4644Deinococcus_radiodurans_gi1580
Nostoc_sp._PCC_7120_gi17228758
Haloarcula_marismortui_ATCC_43
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10966685557931096677637275
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0.1
Eisen, unpublished
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Answers I:
Better Bioinformatics
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Non Homology Based FunctionalPrediction: Phylogenetic Profiles
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Non-Homology Prediction:Phylogenetic Profiles
• Step 1: Search all genes inorganisms of interest againstall other genomes
• Ask: Yes or No, is each genefound in each other species
• Cluster genes by distributionpatterns (profiles)
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Table 3. Presence of MutS Homologs in Complete Genomes Sequences
Species # of MutSHomologs
WhichSubfamilies?
MutLHomologs
BacteriaEscherichia coli K12 1 MutS1 1Haemophilus influenzae Rd KW20 1 MutS1 1Neisseria gonorrhoeae 1 MutS1 1Helicobacter pylori 26695 1 MutS2 -Mycoplasma genitalium G-37 - - -Mycoplasma pneumoniae M129 - - -Bacillus subtilis 169 2 MutS1,MutS2 1Streptococcus pyogenes 2 MutS1,MutS2 1Mycobacterium tuberculosis - - -Synechocystis sp. PCC6803 2 MutS1,MutS2 1Treponema pallidum Nichols 1 MutS1 1Borrelia burgdorferi B31 2 MutS1,MutS2 1Aquifex aeolicus 2 MutS1,MutS2 1Deinococcus radiodurans R1 2 MutS1,MutS2 1
ArchaeaArchaeoglobus fulgidus VC-16, DSM4304 - - -Methanococcus janasscii DSM 2661 - - -Methanobacterium thermoautotrophicum ΔH 1 MutS2 -
EukaryotesSaccharomyces cerevisiae 6 MSH1-6 3+Homo sapiens 5 MSH2-6 3+
MutL and MutS1 Always Together
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Co-Occurrence of Spo Genes
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Co Occurrence of UvrABC
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Co-Occurrence of Muk, SeqA, MutH
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Answers II:
Novelty is good and bad
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Deinococcus radiodurans
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DNA Repair Genes in D.radiodurans Complete Genome
Process Genes in D. radiodurans
Nucleotide Excision Repair UvrABCD, UvrA2Base Excision Repair AlkA, Ung, Ung2, GT, MutM, MutY-Nths,
MPGAP Endonuclease XthMismatch Excision Repair MutS, MutLRecombination Initiation Recombinase Migration and resolution
RecFJNRQ, SbcCD, RecDRecARuvABC, RecG
Replication PolA, PolC, PolX, phage PolLigation DnlJdNTP pools, cleanup MutTs, RRaseOther LexA, RadA, HepA, UVDE, MutS2
White et al, 1999
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Problem:
List of DNA repair gene homologsin D. radiodurans genome is notsignificantly different from other
bacterial genomes of the similar size
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Acidobacteria
Bacteroides
Fibrobacteres
Gemmimonas
Verrucomicrobia
Planctomycetes
Chloroflexi
Proteobacteria
Chlorobi
FirmicutesFusobacteria Actinobacteria
Cyanobacteria
Chlamydia
Spriochaetes
Deinococcus-Thermus Aquificae
Thermotogae
TM6OS-K
Termite GroupOP8
Marine GroupAWS3
OP9
NKB19
OP3
OP10
TM7
OP1OP11
Nitrospira
SynergistesDeferribacteres
Thermudesulfobacteria
Chrysiogenetes
Thermomicrobia
Dictyoglomus
Coprothmermobacter
• At least 40phyla ofbacteria
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Acidobacteria
Bacteroides
Fibrobacteres
Gemmimonas
Verrucomicrobia
Planctomycetes
Chloroflexi
Proteobacteria
Chlorobi
FirmicutesFusobacteria Actinobacteria
Cyanobacteria
Chlamydia
Spriochaetes
Deinococcus-Thermus Aquificae
Thermotogae
TM6OS-K
Termite GroupOP8
Marine GroupAWS3
OP9
NKB19
OP3
OP10
TM7
OP1OP11
Nitrospira
SynergistesDeferribacteres
Thermudesulfobacteria
Chrysiogenetes
Thermomicrobia
Dictyoglomus
Coprothmermobacter
• At least 40phyla ofbacteria
• Most DNAmetabolismstudies in twophyla
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Acidobacteria
Bacteroides
Fibrobacteres
Gemmimonas
Verrucomicrobia
Planctomycetes
Chloroflexi
Proteobacteria
Chlorobi
FirmicutesFusobacteria Actinobacteria
Cyanobacteria
Chlamydia
Spriochaetes
Deinococcus-Thermus Aquificae
Thermotogae
TM6OS-K
Termite GroupOP8
Marine GroupAWS3
OP9
NKB19
OP3
OP10
TM7
OP1OP11
Nitrospira
SynergistesDeferribacteres
Thermudesulfobacteria
Chrysiogenetes
Thermomicrobia
Dictyoglomus
Coprothmermobacter
• At least 40phyla ofbacteria
• Most DNAmetabolismstudies in twophyla
• Deinococcusis distantfrom anywell studiedorganism
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Acidobacteria
Bacteroides
Fibrobacteres
Gemmimonas
Verrucomicrobia
Planctomycetes
Chloroflexi
Proteobacteria
Chlorobi
FirmicutesFusobacteria Actinobacteria
Cyanobacteria
Chlamydia
Spriochaetes
Deinococcus-Thermus Aquificae
Thermotogae
TM6OS-K
Termite GroupOP8
Marine GroupAWS3
OP9
NKB19
OP3
OP10
TM7
OP1OP11
Nitrospira
SynergistesDeferribacteres
Thermudesulfobacteria
Chrysiogenetes
Thermomicrobia
Dictyoglomus
Coprothmermobacter
• At least 40phyla ofbacteria
• Most DNAmetabolismstudies in twophyla
• Deinococcusis distantfrom anywell studiedorganism
• Solution:more studies
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Other peopleOther people
Mom and DadMom and Dad
H. H. OchmanOchman
W. MartinW. Martin
F. RobbF. Robb
J. BattistaJ. BattistaE.E. Orias Orias
D. BryantD. BryantS. OS. O’’NeillNeill
M.M. Eisen Eisen
N. MoranN. Moran
R. MyersR. Myers
C. M. CavanaughC. M. Cavanaugh
P.P. Hanawalt Hanawalt
NSFNSF
J. HeidelbergJ. Heidelberg
T.ReadT.Read
N. WardN. Ward
M-I BenitoM-I Benito
J. C. VenterJ. C. Venter C. FraserC. Fraser
S. S. SalzbergSalzberg
O. WhiteO. White
I. PaulsenI. Paulsen
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