Talk by Jonathan Eisen for GSAC2000 on "Phylogenomics"
•Als PPT, PDF herunterladen•
2 gefällt mir•8,854 views
Talk by Jonathan Eisen for GSAC2000 on "Phylogenomics"
Empfohlen
Weitere ähnliche Inhalte
Was ist angesagt?
Was ist angesagt? (20)
Andere mochten auch
Andere mochten auch (20)
Ähnlich wie Talk by Jonathan Eisen for GSAC2000 on "Phylogenomics"
Ähnlich wie Talk by Jonathan Eisen for GSAC2000 on "Phylogenomics" (20)
Mehr von Jonathan Eisen
Mehr von Jonathan Eisen (20)
Kürzlich hochgeladen
Kürzlich hochgeladen (20)
Talk by Jonathan Eisen for GSAC2000 on "Phylogenomics"
- 1. TIGRTIGR Phylogenomics: Combining Evolutionary Reconstructions and Genome Analysis into a Single Composite Approach 0 250000 500000 750000 1000000 1250000 SubjectOrfPosition 0 250000 500000 750000 1000000 1250000 Query Orf Position Mycobacterium tuberculosis Bacillus subtilis Synechocystis sp. Caenorhabditis elegans Drosophila melanogaster Saccharomyces cerevisiae Methanobacterium thermoautotrophicum Archaeoglobus fulgidus Pyrococcus horikoshii Methanococcus jannaschii Aeropyrum pernix Aquifex aeolicus Thermotoga maritima Deinococcus radiodurans Treponema pallidum Borrelia burgdorferi Helicobacter pylori Campylobacter jejuni Neisseria meningitidis Escherichia coli Vibrio cholerae Haemophilus influenzae Rickettsia prowazekii Mycoplasma pneumoniae Mycoplasma genitalium Chlamydia trachomatis Chlamydia pneumoniae 0.05 changes Archaea Bacteria Eukarya Tmf-penden R-rubrum3 Azs-brasi2 Rm-vanniel Rhb-legum8 Bdr-japoni Spg-capsul Ric-prowaz Ste-maltop Spr-voluta Rub-gelat2 Rcy-purpur Nis-gonor1 Hrh-halc h2 Alm -vin osm Ps-aerugi3 E-coliMyx-xanthu Bde-stolpiDsv-desulfDsb-postgaC-leptum C-butyric4 C-pasteuri Eub-barker C-quercico Hel-chlor2 Acp-laidla M-capricol C-ramosum B-stearoth Eco-faecal Lis-monoc3 B-cereus4 B-subtilis Stc-therm3 L-delbruck L-casei Fus-nuclea Glb-violac Olst-lut_CZeamaysC Nost-muscr Syn-6301 Tnm -lapsum Flx-litora Cy-lytica Emb-brevi2 Bac-fragil Prv-rumcol Prb-difflu Cy-hutchin Flx-canada Sap-grandi Chl-limico Wln-succi2 Hlb-pylor6 Cam-jejun5Stm-ambofa Arb-globif Cor-xerosi Bif-bifidu Cfx-aurant Tmc-roseum Aqu-pyroph env-SBAR12 env-SBAR16 Msr-barker Tpl-acidop Msp-hungat Hf-volcani Mb-formici Mt-fervid1 Tc-celer Arg-fulgid Mpy-kandl1 Mc-vanniel Mc-jannasc env-pJP27 Sul-acalda Thp-tenax env-pJP89 Tt-maritim Fer-island Mei-ruber4 D-radiodur Chd-psitta Acbt-capsl env-MC18 Pir-staley Lpn-illini Lps-interKSpi-stenos Trp-pallidBor-burgdo Spi-haloph Brs-hyodys Fib-sucS85 Tmf-penden R-rubrum3 Azs-brasi2 Rm-vanniel Rhb-legum8 Bdr-japoni Spg-capsul Ric-prowaz Ste-maltop Spr-voluta Rub-gelat2 Rcy-purpur Nis-gonor1 Hrh-halch2 Alm -vinosm Ps-aerugi3 E-coliMyx-xanthu Bde-stolpiDsv-desulfDsb-postgaC-leptum C-butyric4 C-pasteuri Eub-barker C-quercico Hel-chlor2 Acp-laidla M-capricol C-ramosum B-stearoth Eco-faecal Lis-monoc3 B-cereus4 B-subtilis Stc-therm3 L-delbruck L-casei Fus-nuclea Glb-vio lac Olst-lut_CZeamaysC Nost-muscr Syn-6301 Tnm -lapsum Flx-litora Cy-lytica Emb-brevi2 Bac-fragil Prv-rumcol Prb-difflu Cy-hutchin Flx-canada Sap-grandi Chl-limico Wln-succi2 Hlb-pylor6 Cam-jejun5Stm-ambofa Arb-globif Cor-xerosi Bif-bifidu Cfx-aurant Tmc-roseum Aqu-pyroph env-SBAR12 env-SBAR16 Msr-barker Tpl-acidop Msp-hungat Hf-volcani Mb-formici Mt-fervid1 Tc-celer Arg-fulgid Mpy-kandl1 M c-vanniel Mc-jannasc env-pJP27 Sul-acalda Thp-tenax env-pJP89 Tt-maritim Fer-island Mei-ruber4 D-radiodur Chd-psitta Acbt-capsl env-MC18 Pir-staley Lpn-illini Lps-interKSpi-stenos Trp-pallidBor-burgdo Spi-haloph Brs-hyodys Fib-sucS85 Bacteria Archaea Bacteria Archaea A.rRNAtreeofBacterialandArchaealMajorGroups B.GroupswithCompletedGenomesHighlighted A B CD E F A B CD E F A B C D E F A B C D E F A ’ B’ C’ D’ E ’ F’ A B C D E F A’ B’ C’ D’ E ’ F ’ A C D F A’ B’ E’ E. coli E. coli B C D F A’ B’ D’ E ’ V. cholerae A B C D E F A ’ B’ C’ D’ E ’ F’ B1 A1 B2 A2 B3 A3 A2 A1 A2 A3 B2 B1 B3 B2 24 23 22 21 20 19 18171615 14 13 12 11 10 9 6 7 258 26 27 28 29 30 1 2 3 4 5 31 32 B1 3132 6 7 8 9 10 11 12 13 14 15161718 19 20 21 22 23 24 25 26 27 28 29 30 1 2 3 4 5 3132 B3 24 23 22 21 20 19 18171615 14 13 12 11 10 9 6 7 258 26 27 28 29 3 32 31 30 4 5 2 1 A1 3132 6 7 8 9 10 11 12 13 14 15161718 19 20 21 22 23 24 25 26 27 28 29 30 1 2 3 4 5 3132 A2 31 32 6 7 8 9 10 11 12 13 19 18171615 14 20 21 22 23 24 25 26 27 28 29 30 1 2 3 4 5 31 32 A 3 2 6 7 8 9 10 11 12 13 19 18171615 14 20 21 22 23 24 25 26 27 5 4 3 31 30 29 28 1 32 B2 Inversion Around Terminus (*) Inversion Around Terminus (*) Inversion Around Origin (*) Inversion Around Origin (*) * * * * * * * * Figure 4 C ommon Ancestor of A and B 31 32 6 7 8 9 10 11 12 13 14 15161718 19 20 21 22 23 24 25 26 27 28 29 30 1 2 3 4 5 31 32 Three V. cholerae Photolyases Phr.S thyp PHR E. coli O R FA0 0965********* phr.neucr Phr.Tricho Phr.Yeast Phr.B firm phr.strpy phr.haloba PHR STRGR p C RY1.huma p hr.mouse phr2.human phr2.mouse phr.drosop p hr3.Sy nsp O RF02295.Vib ch******** phr.neigo O R F01792.Vib ch******* Phr.Adiant Phr2.Adian Phr3.Adian phr.tomato C RY1 ARATH phr.p hy com C RY2 ARATH PHH1.arath PHR1 SINAL phr.chlamy PHR ANANI phr.Sy nsp PHR SYNY3 phr.Theth Rh.caps M TH F type C la ss I CP D Photolya se s 6-4 P hotolya se s Blue Light R e ce ptors 8-HD F type CPD P hotolya se s Three P hotoly ase H om ologs inV . chole ra e UvrA2 UvrA2 S. coelicolor DrrC S. peuce teus UvrA2 D. radiodurans Duplication inUvrA family UvrA1 UvrA H. influenzae UvrA E. coli UvrA N. gonorrhoaea UvrA R. prowazekii UvrA S. mutans UvrA S. pyogene s 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 OppDF UUP NodI LivF XylG NrtDC PstB MDR HlyB TAP1 CFTR, SUR A. ABC Transporters B. UvrA Subfamily 0 10 20 30 40 50 60 0 5 10 15 20 0 50 100 150 0 5 10 15 20 NumberofSpeciesWithHighHits 0 50 100 150 200 250 Frequency 0 5 10 15 20 PapaBear MamaBear BabyBear 0 100 200 300 400 500 0 5 10 15 20 E.coli
- 2. TIGRTIGR Wolbachia Genome Project • Information is available through TIGRs unfinished genomes service (go to www.tigr.org to find out more) • Also, additional information will soon be available on www.wolbachia.org
- 3. TIGRTIGR
- 4. TIGRTIGR Topics of Discussion • Introduction to phylogenomics • Phylogenomics Examples – Functional prediction – Gene duplication – Genetic exchange within genomes – Gene loss – Horizontal gene transfer – Comparing close relative
- 5. TIGRTIGRTIGRTIGR “Nothing in biology makes sense except in the light of evolution.” T. H. Dobzhansky (1973)
- 6. TIGRTIGR
- 7. TIGRTIGR Uses of Evolutionary Analysis in Molecular Biology • Identification of mutation patterns (e.g., ts/tv ratio) • Amino-acid/nucleotide substitution patterns useful in structural studies (e.g., rRNA) • Sequence searching matrices (e.g., PAM, Blosum) • Motif analysis (e.g., Blocks) • Functional predictions • Classifying multigene families • Evolutionary history puts other information into perspective (e.g., duplications, gene loss) • HIV mutation patterns and classification TIGRTIGR
- 8. TIGRTIGR Evolutionary Studies Improve Most Aspects of Genome Analysis • Phylogeny of species places comparative data in perspective • Evolution of genes and gene families – Functional predictions – Identification of orthologs and paralogs – Species specific mutation patterns • Evolution of pathways – Convergence – Prediction of function • Evolution of gene order/genome rearrangements • Phylogenetic distribution patterns • Identification of novel features
- 9. TIGRTIGR Genome Information and Analysis Improves Studies of Evolution • Complete genome information particularly useful • Unbiased sampling • More sequences of genes • Presence/absence information needed to infer certain events (e.g., gene loss, duplication) • Genome wide mutation and substitution patterns (e.g., strand bias) • Diversification and duplication
- 10. TIGRTIGR Phylogenomic Analysis • There are feedback loop between evolutionary and genome analysis such that for many studies, genome and evolutionary analyses are interdependent. • Therefore, I have proposed that they actually be combined into a single composite approach I refer to as phylogenomics • Phylogenomics involves combining evolutionary reconstructions of genes, proteins, pathways, and species with analysis of complete genome sequences.
- 11. TIGRTIGR Outline of Phylogenomics Gene Evolution Events Phenotype Predictions Database Species tree Presence/AbsenceGene trees Congruence Evol. Distribution F(x) Predictions Pathway Evolution TIGRTIGR
- 12. TIGRTIGR
- 13. TIGRTIGR Uses of Phylogenomics I: Functional Predictions
- 14. TIGRTIGR MutS.Aquae orf.Trepa SPE1.Drome MSH2.Xenla MSH2.Rat MSH2.Mouse MSH2.Human MSH2.Yeast MSH2.Neucr atMSH2.Arath MutS.Borbu orf.Strpy MutS.Bacsu MutS SynspMutS Ecoli orf Neigo MutS Thema MutS Theaq orf.Deira orf.Chltr MSH1.Spombe MSH1.Yeast MSH3.Yeast Swi4.Spombe Rep3.Mouse hMSH3.Human orf.Arath MSH6.Yeast GTBP.Human GTBP.Mouse MSH6.Arath orf Strpy yshD Bacsu MSH5 Caeel hMHS5 human MSH5 Yeast MutS.Metth orf Borbu MutS2 Aquae MutS Synsporf Deira MutS.Helpy sgMutS.Saugl MSH4.Yeast MSH4.Caeel hMSH4.Human A. Aquae Trepa Fly Xenla Rat Mouse Human Yeast Neucr Arath Borbu Strpy Bacsu Synsp Ecoli Neigo Thema TheaqDeira Chltr Spombe Yeast Yeast Spombe Mouse Human Arath Yeast Human Mouse Arath MutS2.Metth MutS2.Saugl StrpyBacsu Caeel Human Yeast Borbu Aquae Synsp Deira Helpy Yeast Caeel Human MSH4 MSH5 MutS2 MutS1 MSH1 MSH3 MSH6 MSH2 B. Aquae Trepa Xenla Neucr Arath Borbu Synsp Neigo Thema Deira Chltr Spombe Spombe Arath Mouse Mouse Fly Rat Mouse Human Yeast Strpy Bacsu Ecoli Theaq Yeast Yeast Human Yeast Human Arath StrpyBacsu Human MutS2-MetthBorbu Aquae Synsp Deira Helpy MutS2-Saugl Caeel Yeast Yeast Caeel Human MSH4 MSH5 MutS2 MutS1 MSH1 MSH3 MSH6 MSH2 C. MutS2StrpyBacsu MutS2.MetthBorbu Aquae Synsp Deira Helpy MutS2.Saugl Caeel Yeast Yeast Caeel Human Human MSH4 Segregation & Crossover MSH5 Segregation & Crossover Fly Mouse Human Yeast Aquae Trepa Xenla Neucr Arath Borbu Synsp Neigo Thema Deira Chltr Spombe Spombe Arath Arath MutS1 All MMR (Bacteria) Rat Strpy Bacsu Ecoli Theaq Yeast Yeast Mouse Human Yeast Human Mouse MSH1 MMR in Mitochondria MSH3 MMR of Large Loops in Nucleus MSH6 MMR of Mismatches and Small Loops in Nucleus MSH2 All MMR in Nucleus D.
- 15. TIGRTIGR 4 F17L22 170 Arabidopsis thali 4455279 Arabidopsis thaliana 1049068 Lycopersicon esculentu Homo sapiens 5514652 Drosophila melanogaste Drosophila melanogaster2 123725 Caenorhabditis elegans 6606113 Capronia mansonii RpoII.Yeast.YOR151C 107346 Schizosaccharomyces pom 151348 Euplotes octocarinatus 265427 Euplotes octocarinatus 3845258 Plasmodium falciparum RpoIII.Drome RpoIII.Drome.7303535 EGAD 114464 Caenorhabditis ele RpoIII.Yeast.172383 EGAD 145012 Schizosaccharomyce RpoIII.Neucr.7800864 ARATH5 K18C1 1 Aeropyrum pernix EGAD 8025 Sulfolobus acidocald 5458046 Pyrococcus abyssi PH1546 Pyrococcus horikoshii Thermococcus celer EGAD 14667 Methanococcus vanni MJ1040 Methanococcus jannaschi AF1886 Archaeoglobus fulgidus Halobacterium halobium Thermoplasma acidophilum RPB2 Methanobacterium thermoau atmystery.BAB02021 ARATH3 MRC8.7 ARATH3 MYM9.12 6723961 Schizosaccharomyces po RpoI.Yeast.YPR010C RpoI.Neucr.3668171 RPA2 Rattus norvegicus Mus musculus RpoI.Drome.7296211 Caenorhabditis elegans 92131 Euplotes octocarinatus ARATH1 T1P2.15 ARATH1 F1N18.2 1492072Molluscum contagiosum v 439046 Variola major virus 1143635 Variola virus 2772787 Vaccinia virus 323395 Cowpox virus 6578643 Rabbit fibroma virus 6523969 Myxoma virus 6682809 Yaba monkey tumor viru 7271687 Fowlpox virus 4049822 Melanoplus sanguinipes 2887 Kluyveromyces lactis EGAD 151364 Sacch kluyveri 1369760 Borrelia burgdorferi BB0389 Borrelia burgdorferi TP0241 Treponema pallidum 6652714 Rickettsia massiliae 6652723 Rickettsia sp. Bar29 6652720 Rickettsia conorii RP140 Rickettsia prowazekii 6960339 Salmonella typhimurium EGAD 1084 Salmonella choleraes EC3987 Escherichia coli EGAD 23892 Buchnera aphidicola HI0515 Haemophilus influenzae EGAD 6020 Pseudomonas putida RPOB Coxiella burnetii 3549149 Legionella pneumophila RPOB Neisseria meningitidis HP1198 Helicobacter pylori 6967949 Campylobacter jejuni AA1339 Aquifex aeolicus BS0107 Bacillus subtilis 4512396 Bacillus halodurans 6002201 Listeria monocytogenes EGAD 32012 Staphylococcus aure EGAD 32011 Spiroplasma citri MG341 Mycoplasma genitalium MP326 Mycoplasma pneumoniae 6899151 Ureaplasma urealyticum Rv0667 Mycobacterium tuberculo Mycobacterium leprae 7144498 Mycobacterium smegmati EGAD 39063 Mycobacterium smegm GP 7331268 Amycolatopsis medit 7248348 Streptomyces coelicolo 7573273 Thermus aquaticus DR0912 Deinococcus radiodurans TM0458 Thermotoga maritima EGAD 74970 80693 Heterosigma c EGAD Odontella sinensis EGAD 60306 Spinacia oleracea EGAD Nicotiana tabacum 6723742 Oenothera elata 5457427 Sinapis alba 5881686 Arabidopsis thaliana 4958867 Triticum aestivum EGAD 76270 Zea mays RPOB Oryza sativa EGAD Pinus thunbergii EGAD Marchantia polymorpha 7259525 Mesostigma viride 5880717 Nephroselmis olivacea RPOB Guillardia theta sll1787 Synechocystis PCC6803 EGAD 75526 Porphyra purpurea 6466433 Cyanidium caldarium EGAD 76712 Cyanophora paradoxa RPOB Chlorella vulgaris EGAD 76424 Euglena gracilis 5231258 Toxoplasma gondii 6492294 Neospora caninum EGAD 83446 Plasmodium falcipar 100 78 100 85 93 83 100 79 100 100 100 100 100 100 94100 100 74 99 100 99 100 100 99 9480 100 100 100 100 59 100 100 99 56100 100 100 100 58 95 100 97 63 95 100 100 100 81 100 100 100 59 60 99 100 100 94 100 100 69 100 77 100 97 100 71 100 99 58 83 100100 100 99 100 98 100 100 61 99 75 100 73 100 100 59 100 100 72 72 98 52 98 59 100 100 a Novel RNA Polymerase in A. thaliana Archaeal IV II III I Viral Bacterial - RpoB Plastid- RpoBs
- 16. TIGRTIGR Novel Large Subunit Rubisco in Chlorobium tepidumAgathis.gi3982533 Agathis.gi3982549 Araucaria.gi3982517 Agathis.gi3982535 Agathis.gi3982541 Venturiella.gi4009420 Leucobryum.gi6230571 Mougeotia.gi1145415 Anabaena.gi68158 Thife.gi2411435 Thiin.gi4105518 Metja.gi2129276 Pyrho.gi|3257353 Pyrab.gi|5458634 Pyr karaensis.gi3769302 Arcfu.gi2648911 Arcfu.gi2648975 Bacsu.gi2633730 Chlte.ORF02314 100 100 96 54 99 58 66 59 100 100 82 67 100 100 100 93 Type X Type I Rubisco Large Subunit Phylogeny
- 17. TIGRTIGR Evolutionary Analysis Improves Functional Prediction • Many examples of using phylogenetic trees – DNA repair - Eisen – Transporters – Paulsen and Saier – Transcription factors – Atchley – Kinases – Henikoff • Phylogenetic profiles and domain patterns also useful
- 18. TIGRTIGR Uses of Phylogenomics II: Gene Duplication
- 19. TIGRTIGR Why Duplications Are Useful to Identify • Allows division into orthologs and paralogs • Aids functional predictions • Recent duplications may be indicative of species’ specific adaptations • Helps identify mechanisms of duplication • Can be used to study mutation processes in different parts of genome
- 20. TIGRTIGR Expansion of MCP Family in V. cholerae E.coligi1787690 B.subtilisgi2633766 Synechocystissp. gi1001299 Synechocystissp. gi1001300 Synechocystissp. gi1652276 Synechocystissp.gi1652103 H.pylori gi2313716 H.pylori99 gi4155097 C.jejuniCj1190c C.jejuniCj1110c A.fulgidusgi2649560 A.fulgidusgi2649548 B.subtilisgi2634254 B.subtilisgi2632630 B.subtilisgi2635607 B.subtilisgi2635608 B.subtilisgi2635609 B.subtilisgi2635610 B.subtilisgi2635882 E.coligi1788195 E.coligi2367378 E.coligi1788194 E.coligi1789453 C.jejuniCj0144 C.jejuniCj0262c H.pylori gi2313186 H.pylori99 gi4154603 C.jejuniCj1564 C.jejuniCj1506c H.pylori gi2313163 H.pylori99 gi4154575 H.pylori gi2313179 H.pylori99 gi4154599 C.jejuniCj0019c C.jejuniCj0951c C.jejuniCj0246c B.subtilisgi2633374 T.maritima TM0014 T.pallidumgi3322777 T.pallidumgi3322939 T.pallidumgi3322938 B.burgdorferi gi2688522 T.pallidumgi3322296 B.burgdorferi gi2688521 T.maritima TM0429 T.maritima TM0918 T.maritima TM0023 T.maritima TM1428 T.maritima TM1143 T.maritima TM1146 P.abyssiPAB1308 P.horikoshiigi3256846 P.abyssiPAB1336 P.horikoshiigi3256896 P.abyssiPAB2066 P.horikoshiigi3258290 P.abyssiPAB1026 P.horikoshiigi3256884 D.radiodurans DR A00354 D.radiodurans DRA0353 D.radiodurans DRA0352 P.abyssiPAB1189 P.horikoshiigi3258414 B.burgdorferi gi2688621 M.tuberculosisgi1666149 V .c hole ra eV C0 5 1 2 V . c hol e ra eV CA1 0 3 4 V .c hole ra eV CA 0 9 7 4 V .c hole raeV CA 0 06 8 V . chol e ra eV C0 8 2 5 V . c hol e ra eV C0 28 2 V .c hol e raeV CA 0 9 0 6 V . chol e ra eV CA0 9 7 9 V .c hol e raeV CA 1 0 5 6 V . c hol e ra eV C1 64 3 V . c hol e ra eV C2 1 6 1 V .c hole ra eV CA 09 2 3 V .c hole raeV C0 5 1 4 V . c hol e ra eV C1 8 6 8 V . c hol era eV CA0 7 7 3 V .c hole raeV C1 3 1 3 V . c hol era eV C1 8 5 9 V . c hole ra eV C14 1 3 V .c hol e raeV CA 0 2 6 8 V .c hol e raeV CA0 6 5 8 V . c hole ra eV C14 0 5 V . c hol e ra eV C1 2 9 8 V . c hol e ra eV C1 2 4 8 V . c hol era eV CA0 8 6 4 V . c hole ra eV CA0 1 7 6 V. c hol e ra eV CA0 2 2 0 V .c hole ra eV C1 2 8 9 V .c hole ra eV CA 10 6 9 V . c hol e ra eV C2 43 9 V . chol e ra eV C1 9 6 7 V . chol e ra eV CA0 0 3 1 V . c hole ra eV C18 9 8 V . chol e ra eV CA0 6 6 3 V .c hole ra eV CA 0 9 8 8 V . c hol era eV C0 2 1 6 V . c hol era eV C0 4 4 9 V .c hole ra eV CA 0 0 0 8 V . c hole ra eV C14 0 6 V . chol e ra eV C1 5 3 5 V .c hole ra eV C0 8 4 0 V . c hol e raeV C0 0 98 V .c hole ra eV CA 1 0 9 2 V .c hole ra eV C1 4 0 3 V .c hole ra eV CA1 0 8 8 V . c hol e ra eV C1 3 9 4 V .c hole ra eV C0 6 2 2 NJ * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * ** * * * * * * * * * * * * * * * * * * * * * *
- 21. TIGRTIGR ArsA Duplications in C. tepidum Chlvi.497325 CHLTE ORF02621 CHLTE ORF00955 CHLTE ORF03444 SYNSP 1001709 CHLTE ORF02844 AQUAE 2983270 CHLTE ORF03869 CHLTE ORF02611 SYNSP 1651887 MCYTU - 2960104 PYRAB PAB1555 AQUAE 2983014 Potato.5824321 Arath.6056208 Metth.2622629 METJA 1591774 Acidiphilum.2879919 1061416 Ecoli.78323 Sinorhizobium.5802945 Halsp.2822401 Mouse.2745900 Human.2905657 Human.1616741 Drome.7304195 CELEG ZK637.5 Yeast.1199549 Yeast.6320103 Spombe.7211054 100 35 16 26 100 80 80 45 100 100 100 77 51 39 34 100 100 75 100 100 77 87 97 100 38 88 100 ArsA Tree
- 22. TIGRTIGR Levels of Paralogy Within A Genome
- 23. TIGRTIGR C. pneumoniae Paralogs - All 0 250000 500000 750000 1000000 1250000 SubjectOrfPosition 0 250000 500000 750000 1000000 1250000 Query Orf Position
- 24. TIGRTIGR C. pneumoniae Paralogs - Top 0 250000 500000 750000 1000000 1250000 SubjectOrfPosition 0 250000 500000 750000 1000000 1250000 Query Orf Position
- 25. TIGRTIGR C. pneumoniae Paralogs – Recent 0 250000 500000 750000 1000000 1250000 SubjectOrfPosition 0 250000 500000 750000 1000000 1250000 Query Orf Position
- 26. TIGRTIGR Uses of Phylogenomics III: Genetic Exchange within Genomes
- 27. TIGRTIGR
- 28. TIGRTIGR Uses of Phylogenomics IV: Gene Loss
- 29. TIGRTIGR Why Gene Loss is Useful to Identify • Indicates that gene is not absolutely required for survival • Correlated loss of same gene in different species may indicate selective advantage of loss of that gene • Correlated loss of genes in a pathway suggests a conserved association among those genes
- 30. 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 ( ) or Absence of Gene Species Abbreviation Kingdom Example of Tracing Gene Loss TIGRTIGR
- 32. TIGRTIGR Need for Phylogenomics Example: Gene Duplication and Loss • Genome analysis required to determine number of homologs in different species • Evolutionary analysis required to divide into orthology groups and identify gene duplications • Genome analysis is then required to determine presence and absence of orthologs • Then loss of orthologs can be traced onto evolutionary tree of species
- 33. TIGRTIGR Uses of Phylogenomics V: Comparison of Closely Related Genomes
- 34. TIGRTIGR V. cholerae vs. E. coli All Hits 0 1000000 2000000 3000000 4000000 5000000E.coliCoordinates 0 1000000 2000000 3000000 V. cholerae CoordinatesTIGRTIGR
- 35. TIGRTIGR V. cholerae vs. E. coli Top Hits 0 1000000 2000000 3000000 4000000 5000000 E.coliCoordinates 0 1000000 2000000 3000000 V. cholerae CoordinatesTIGRTIGR
- 36. TIGRTIGR V. cholerae vs. E. coli Only if EC-Orf is Closest in All Genomes 0 1000000 2000000 3000000 4000000 5000000 E.coliCoordinates 0 1000000 2000000 3000000 V. cholerae Coordinates TIGRTIGR
- 37. TIGRTIGR V. cholerae vs. E. coli F+R 0 1000000 2000000 3000000 4000000 5000000 Bert Ecoli R Ecoli
- 38. TIGRTIGR Uses of Phylogenomics VI: Evolution Within Species
- 40. 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 0.40 0.45 0.50 0.55 0.60 0.65 0.70 0.75 0.80 0.85 0.90 0.95 1.00 maximum average minimum 2 9 0 4 3 1 3 5 3 1 9 4 4 0 9 0 4 2 3 9 4 2 4 6 4 5 8 9 5 1 9 8 4 2 5 1 1 0 4 9 2 4C 6 6B 7 8C 9B 11B 14 15 15B 18C 4 8 12 16 18 M U S S E R S m e a r Si te 2 1 3 4 Character
- 41. TIGRTIGR Uses of Phylogenomics VII: Horizontal Gene Transfer and Species Evolution
- 43. TIGRTIGR Horizontal Gene Transfer from Doolittle, 1999
- 44. TIGRTIGR Why Gene Transfers Are Useful to Identify • Laterally transferred genes frequently involved in environmental adaptations and/or pathogenicity • Helps identify transposons, integrons, and other vectors of gene transfer • Helps identify species associations in the environment • Prediction of organellar targeting of nuclear encoded genes
- 45. TIGRTIGR Horizontal Gene Transfer I from Doolittle, 1999
- 46. 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 Matches to Prokaryotes CAUCR BACSU ECOLI MYCTU SYNSP
- 47. 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 RICPR CAUCR HELPY SYNSP AQUAE DEIRA THEMA AERPE ARCFU METJA METTH PYRAB CELEG YEAST DROME B A E
- 48. TIGRTIGR Possible Plastid ORFs • So far, over 900 ORFs are candidates for being derived from the plastid genome some time in the past – 50 have best match to plastid genomes from other plants – more than 800 have best match to Syn. sp. complete genome – 100 have best matches to proteins from incomplete cyanobacterial genomes but no match to the proteins from Syn. sp. – incredible diversity of putative functions as well as many conserv hypothetical
- 49. TIGRTIGR Organellar HSP60s DROMECG12101 DROMECG7235 DROMECG2830 DROMECG16954 ARATH At2g33210 ARATH F14O13.19 ARATH MCP4.7 YEAST SW CAUCR ORF03639 RICPR gi|3861167 ECOLI gi|1790586 NEIMEb gi|7227233. AQUAE gi|2984379 CHLPN gi|4376399| DEIRA ORF02245 BACSU gi|2632916 SYNSP gi|1652489 SYNSP gi|1001103 ARATH At2g28000 ARATH MRP15.11 MCYTU gi|2909515 MCYTU gi|1449370 THEMA TM0506 BBUR gi|2688576 TREPA gi|3322286 PORGI ORF00933 CHLTE ORF00173 HELPY gi|2313084 Mitochondrial Forms α-Proteo Cyanobacteria Plastid Forms
- 50. TIGRTIGR Evolutionary Genome Scanning • Distribution patterns/phylogenetic profiles • Patterns of evolution (ds/dn, correlations, constraints) • Lateral gene transfers (organellar genes, Pathogenicity islands) • Subdividing gene families • Functional predictions (gene trees, PG profiles) • Gene duplications • Gene loss • Specialization • Comparing close relatives • Species evolution
- 51. TIGRTIGR Evolutionary Diversity Still Poorly Represented in Complete Genomes Tmf-penden R-rubrum3 Azs-brasi2 Rm-vanniel Rhb-legum8 Bdr-japoni Spg-capsul Ric-prowaz Ste-maltop Spr-voluta Rub-gelat2 Rcy-purpur Nis-gonor1 Hrh-halch2 Alm-vinosm Ps-aerugi3 E-coliMyx-xanthu Bde-stolpiDsv-desulfDsb-postgaC-leptum C-butyric4 C-pasteuri Eub-barker C-quercico Hel-chlor2 Acp-laidla M-capricol C-ramosum B-stearoth Eco-faecal Lis-monoc3 B-cereus4 B-subtilis Stc-therm3 L-delbruck L-casei Fus-nuclea Glb-violac Olst-lut_CZeamaysC Nost-muscr Syn-6301 Tnm-lapsum Flx-litora Cy-lytica Emb-brevi2 Bac-fragil Prv-rumcol Prb-difflu Cy-hutchin Flx-canada Sap-grandi Chl-limico Wln-succi2 Hlb-pylor6 Cam-jejun5Stm-ambofa Arb-globif Cor-xerosi Bif-bifidu Cfx-aurant Tmc-roseum Aqu-pyroph env-SBAR12 env-SBAR16 Msr-barker Tpl-acidop Msp-hungat Hf-volcani Mb-formici Mt-fervid1 Tc-celer Arg-fulgid Mpy-kandl1 M c-vanniel Mc-jannasc env-pJP27 Sul-acalda Thp-tenax env-pJP89 Tt-maritim Fer-island M ei-ruber4 D-radiodur Chd-psitta Acbt-capsl env-MC18 Pir-staley Lpn-illini Lps-interKSpi-stenos Trp-pallid Bor-burgdo Spi-haloph Brs-hyodys Fib-sucS85 Tmf-penden R-rubrum3 Azs-brasi2 Rm-vanniel Rhb-legum8 Bdr-japoni Spg-capsul Ric-prowaz Ste-maltop Spr-voluta Rub-gelat2 Rcy-purpur Nis-gonor1 Hrh-halch2 Alm-vinosm Ps-aerugi3 E-coliMyx-xanthu Bde-stolpiDsv-desulfDsb-postgaC-leptum C-butyric4 C-pasteuri Eub-barker C-quercico Hel-chlor2 Acp-laidla M-capricol C-ramosum B-stearoth Eco-faecal Lis-monoc3 B-cereus4 B-subtilis Stc-therm 3 L-delbruck L-casei Fus-nuclea Glb-violac Olst-lut_CZeamaysC Nost-muscr Syn-6301 Tnm -lapsum Flx-litora Cy-lytica Emb-brevi2 Bac-fragil Prv-rumcol Prb-difflu Cy-hutchin Flx-canada Sap-grandi Chl-limico Wln-succi2 Hlb-pylor6 Cam-jejun5Stm-ambofa Arb-globif Cor-xerosi Bif-bifidu Cfx-aurant Tmc-roseum Aqu-pyroph env-SBAR12 env-SBAR16 Msr-barker Tpl-acidop Msp-hungat Hf-volcani Mb-formici Mt-fervid1 Tc-celer Arg-fulgid Mpy-kandl1 M c-vanniel Mc-jannasc env-pJP27 Sul-acalda Thp-tenax env-pJP89 Tt-maritim Fer-island M ei-ruber4 D-radiodur Chd-psitta Acbt-capsl env-MC18 Pir-staley Lpn-illini Lps-interKSpi-stenos Trp-pallid Bor-burgdo Spi-haloph Brs-hyodys Fib-sucS85 Bacteria Archaea Bacteria Archaea A.rRNAtreeofBacterialandArchaealMajorGroups B.GroupswithCompletedGenomesHighlighted
- 52. TIGRTIGR Acknowledgements • Genome duplications: S. Salzberg, J. Heidelberg, O. White, A. Stoltzfus, J. Peterson • Genome sequences and analysis: J. Heidelberg, T. Read, H. Tettelin, K. Nelson, J. Peterson, R. Fleischmann, D. Bryant • Horizontal transfers: K. Nelson, W. F. Doolittle • TIGR: C. Fraser, J. Venter, M-I. Benito, S. Kaul, Seqcore • $$$: DOE, NSF, NIH, ONR
- 53. TIGRTIGR True Phylogenetic Methods Work Best MutS2.Syns MutS2.Bacs MutS2.Help MutS2.Deir Mutsl.Mett MSH4.Celeg MSH4.Yeast MSH4.human mMutS.Saco MSH3.yeast C23C11.Spo MSH1.Yeast MSH3.Human REP1.Mouse GTBP.Mouse GTBP.Human MSH6.Yeast MSH5.Human MSH5.Celeg MSH5.Yeast MSH2.Human MSH2.Mouse MSH2.Yeast MutS.Ecoli MutS.Synsp MutS.Deira MutS.Bacsu M utS.Ecoli M utS.Synsp M utS.B acsu M utS.Deira M SH 2.H uman M SH 2.M ouse M SH 2.Yeast M SH 3.H uman R EP1.M ouse G TB P.M ouse G TB P.H uman M SH 6.Yeast C 23C 11.Sp o M SH 1.Yeast M SH 3.yeast M SH 4.C eleg M SH 4.human M SH 5.C eleg M SH 5.Yeast mM utS.Saco M SH 5.H uman M SH 4.Yeast M utS2.Syns M utS2.B acs M utS2.Deir M utS2.H elp M utsl.M ett UPGMANeighbor-Joining
- 54. TIGRTIGR Reconciling a Tree of Life in the Context of Lateral Gene Transfer
- 55. TIGRTIGR Whole Genome Phylogeny Huynen, Snel & Bork, 1999
- 56. TIGRTIGR rRNA vs. Whole Genome Trees Mycobacterium tuberculosis Bacillus subtilis Synechocystis sp. Caenorhabditis elegans Drosophila melanogaster Saccharomyces cerevisiae Methanobacterium thermoautotrophicum Archaeoglobus fulgidus Pyrococcus horikoshii Methanococcus jannaschii Aeropyrum pernix Aquifex aeolicus Thermotoga maritima Deinococcus radiodurans Treponema pallidum Borrelia burgdorferi Helicobacter pylori Campylobacter jejuni Neisseria meningitidis Escherichia coli Vibrio cholerae Haemophilus influenzae Rickettsia prowazekii Mycoplasma pneumoniae Mycoplasma genitalium Chlamydia trachomatis Chlamydia pneumoniae 0.05 changes Archaea Bacteria Eukarya
- 57. TIGRTIGR Serratia marcescens Proteus mirabilis Proteus vulgaris Escherichia coli Erwinia carotovora Yersinia pestis Enterobacter agglomerans Vibrio anguillarum Vibrio cholerae Haem ophilus influenzae Pseudomonasfluorescens Pseudomonasputida Pseudomonasaeruginosa Azotobacter vinelandii Acinotobactercalcoaceticus Methylophilusmethylotrophus Methylomonasclara Methylobacillusflagellatum Burkholderia cepacia Bordetella pertussis Xanthomonas oryzae Legionella pneumophila Acidiphilum facilis Thiobacillus ferrooxidans Neisseria gonorrhoeae Rhizobium viciae Myxococcus xanthus1 Myxococcus xanthus2 Campylobacter jejuni StreptomycesviolaceusStreptomyceslividans Streptomycesambofaciens Mycobacteriumleprae Mycobacteriumtuberculosis Corynebacteriumglutamicum Arabidopis thaliana CPST Synechococcussp.PCC7002 Synechococcussp.PCC7942 Anabaenavariabilis Thermotoga maritima Lactococcuslactis Streptococcuspneumoniae Staphylococcusaureus Bacillussubtilis Acholeplasm a laidlawii Borrelia burgdorferi Mycoplasma pulmonis Mycoplasma mycoides Bacteroides fragilis Chlaymida trachomatis Thermus thermophilus Thermus aquaticus Deinococcus radiodurans Aquifex pyrophilus 0.10 α γ1 γ2 β Gram '+' High GC Cyanobacteria Gram '+' Low GC D/T Magnetospirillum magnetotacticum Helicobacter pylori ε δ 95 98 79 100 100 100 90 63 100 94 84 100 95 10088 93 91 75 100 100 100 100 100 8398 100 100 100 Rhizobium phaseoli Agrobacterium tumefaciens Rhizobium meliloti Brucella abortus Rhodobacter sphaeroides Rhodobacter capsulatus Rickettsia prowazekii Acetobacter polyoxogenes 72 97 78 100 71 100 100 77 88 100 61 55 54 48 49 42 48 46 50 63 46 100 40
- 58. TIGRTIGR TIGTIG RR OtherOther peoplepeople Mom and DadMom and Dad S. KarlinS. Karlin M. FeldmanM. Feldman A. M. CampbellA. M. Campbell R. FernaldR. Fernald R. ShaferR. Shafer D. AckerlyD. Ackerly D. GoldsteinD. Goldstein M. EisenM. Eisen J. CourcelleJ. Courcelle R. MyersR. Myers C. M. CavanaughC. M. Cavanaugh P. HanawaltP. Hanawalt NSFNSF J. HeidelberJ. Heidelber T.ReadT.Read S. KaulS. Kaul M-I BenitoM-I Benito J. C. VenterJ. C. VenterC. FraseC. Fraser S. SalzbergS. Salzberg O. WhiteO. White K. NelsonK. Nelson $$$$$$ ONRONR DOEDOE NIHNIH H. TettelinH. Tettelin
- 59. 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 Category Arc/Bac
- 60. TIGRTIGR Uses of Phylogenomics VII: Specialization
- 61. 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 20 NumberofSpeciesWithHighHits 0 50 100 150 200 250 Frequency 0 5 10 15 20 PapaBear MamaBear BabyBear 0 100 200 300 400 500 0 5 10 15 20 E.coli
- 62. TIGRTIGR Megaplasmid I: Iron Utilization/Iron Transport ORFB040 Na+/H+ antiporterORFB040 Na+/H+ antiporter ORFB042 iron ABC transporter, ATP-binding proteinORFB042 iron ABC transporter, ATP-binding protein ORFB044 iron ABC transporter, permease proteinORFB044 iron ABC transporter, permease protein ORFB045 iron ABC transporter, permease proteinORFB045 iron ABC transporter, permease protein ORFB046 iron-chelator utilization proteinORFB046 iron-chelator utilization protein ORFB047 iron ABC transporter, periplasmic substrate bpORFB047 iron ABC transporter, periplasmic substrate bp ORFB067 putative metal binding proteinORFB067 putative metal binding protein ORFB141 iron-chelator utilization proteinORFB141 iron-chelator utilization protein ORFB074 hemin ABC transporter, periplasmic hemin bpORFB074 hemin ABC transporter, periplasmic hemin bp ORFB075 hemin ABC transporter, permease proteinORFB075 hemin ABC transporter, permease protein ORFB076 hemin ABC transporter, ATP-binding proteinORFB076 hemin ABC transporter, ATP-binding protein
- 63. TIGRTIGR Carboxydothermus hydrogenoformans • Isolated in Yellowstone • Thermophile (grows at 80°C) • Anaerobic • Grows on CO (Carbon Monoxide) • Produces hydrogen gas • Low GC gram postive species • Many Archaeal-like genes
- 64. TIGRTIGR Wolbachia sp. • Endosymbionts of many invertebrates • We are sequencing the symbiont of the fruit fly and a parasite Brugia malayi. • Some of required for host survival, some are pathogens (e.g., in wasps, Wolbachia kill all male offspring) • Member of the α-Proteobacteria
- 65. TIGRTIGR Methylococcus capsulatus • Member of the γ-Proteobacteria • Grows on methane • Collaboration with University of Bergen in Norway who are working on using this species as Salmon feed
- 66. TIGRTIGR Figure 6. Citrate lyase domains Human Citrate lyase CelegCitrate lyase Cyanophora A. thaliana F5E6.2 chrIII Chlorobium 1164 Spombe Citrate synthase I Succinyl Co-A Synthase alpha Succinyl Co-A Synthase beta Chlorobium 2435 A. thaliana - many Bacteria Eukaryotic mitochondria Chlorobium 3733 Bacteria Chlorobium 1167 A. thaliana - many Bacteria
- 67. TIGRTIGR Chlorobium tepidum Strain TLS C. tepidum mat in highly sulfidic “Travelodge Stream”, Rotorua, New Zealand (from Castenholz and Pierson, 1995) Phase contrast photomicrograph of the 48-hours culture and electron micrograph of thin cell section (from Wahlund et al, 1991)
- 68. 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 H 2 C (CH3 )3 ethyl propyl isobutyl neopentyl farnesyl C H 2 C H 3 N N N N O H 3 C C H 3H 3C C H 2CH 3 O O M g CH 3 COO C H3 CH CH 2 N N N N O H 3 C C H 3H 3C C H 2CH 3 C C H 3 O O M g CH 3 COO C H3 O Chlorophylls Found in Chlorobium tepidum Chlorophyll a-670Bacteriochlorophyll a Bacteriochlorophyll c ∆-2, 6 phytadienol phytol
- 69. TIGRTIGR Protein Duplications • Of 14,881 ORFs with matches to a complete genome, 13,092 have a best match to another A. thaliana ORF • Two major classes – tandem duplications – large chromosomal duplications
- 70. TIGRTIGR Best Matches to Complete Genomes 0 1000 2000 3000 4000 BestMatches CHLTE PORGI BACSU MCYTU BBUR TREPA CHLPN ECOLI NEIME RICPR CAUCR HELPY SYNSP AQUAE DEIRA THEMA AERPE ARCFU METJA METTH PYRAB CELEG YEAST DROME B A E
- 72. TIGRTIGR U28187 Nasonia longicornis IV7 U28188 Nasonia vitripennis LbII U28182 Nasonia giraulti RV2 A U28203 Nasonia giraulti RV2 B U28204 Nasonia longicornis IV7 U28205 Nasonia vitripennis LbII Brugia malayi MB Brugia malayi CB Brugia pahangi Litomosoides sigmodontis Litomosoides carinii Dirofilaria immitis dog Dirofilaria immitis Jap Dirofilaria immitis cat Dirofilaria repens MI Dirofilaria repens PV Onchocerca gibsoni Onchocerca ochengi Onchocerca gutturosa Anaplasma marginale 72 59 100 98 100 69 99 100 100 61 58 100 100 100 94 Bootstrap Phylogenetic analysis using ftsZ sequences A B C D Figure 4: The phylogenetic tree below adapted from Bandi et. al. 1999 (12) shows the four major Wolbachia clades with representatives of nematode and insect Wolbachia .
- 73. TIGRTIGR Uses of Phylogenomics II: Knowing when to Not Predict Functions
- 74. TIGRTIGR
- 75. TIGRTIGR Evolution of Uracil Glycosylase • Ung activity has evolve many times (many non- homologous proteins have uracil-DNA glycosylase activity) • Therefore, absence of homologs of these genes should not be used to infer likely absence of activity • However, presence of homologs of Ung and MUG genes can be used to indicate presence of activity because all homologs of these genes have this activity
- 76. TIGRTIGR Evolution of Photoreactivation • All known enzymes that perform photoreactivation are part of a single large photolyase gene family • Some members of the family do not function as photolyases, but instead work as blue-light receptors • If a species does not encode a member of the photolyase gene family, it likely does not have photoreactivation capability • If a species encodes a photolyase, one cannot conclude it has photolyase activity • Position of photolyase homologs within photolyase tree helps predict what activities they have
- 77. TIGRTIGR Evolution of Alkyltransferases • All known alkyltransferases share a conserved, homologous alkyltransferase domain • Therefore, if a species does not encode any protein with this domain, it likely does not have alkyltransferase activity • If a species does encode an member of this gene family, it likely has alkyltransferase activity
- 78. TIGRTIGR Examples of Horizontal Transfers • Antibiotic resistance genes on plasmids • Insertion sequences • Pathogenicity islands • Toxin resistance genes on plasmids • Agrobacterium Ti plasmid • Viruses and viroids • Organelle to nucleus transfers
- 79. TIGRTIGR Archaeal genes in bacterial genomesArchaeal genes in bacterial genomes** Bacterial speciesBacterial species Best hits to ArchaealBest hits to Archaeal Thermotoga maritimaThermotoga maritima 451 (24%)451 (24%) Aquifex aeolicusAquifex aeolicus 246 (16%)246 (16%) SynechocystisSynechocystis sp.sp. 126 (4%)126 (4%) Borrelia burgdorferiBorrelia burgdorferi 45 (3.6%)45 (3.6%) Escherichia coliEscherichia coli 99 (2.3%)99 (2.3%) ** 1010-5-5 over 60% of sequenceover 60% of sequence
- 80. TIGRTIGR • Possibilitiy of gene transfer criticized because of possibility of shared descent • C. tepidum – green sulfur bacteria – 15-20% • C. hydrogenoformans – low GC gram + - ~25%
Hinweis der Redaktion
- <number>