Jonathan Eisen lecture for MBL Molecular Evolution Course 2003


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  • Jonathan Eisen lecture for MBL Molecular Evolution Course 2003

    1. 1. TIGRTIGR
    2. 2. TIGRTIGR
    3. 3. TIGRTIGR Topics of Discussion • Introduction to genome sequencing and analysis • Need for “phylogenomic” approaches • Phylogenomic examples – Species evolution – Lateral vs. vertical evolution – Gene function – Gene duplications – Genome rearrangements
    4. 4. TIGRTIGR The Institute for Genomic Research (TIGR) • A not for profit institution, staff ~350 • Funded primarily by government grants • Departments: – Research Departments – Bioinformatics – Sequencing Core
    5. 5. TIGRTIGR Fleischmann et al. 1995
    6. 6. TIGRTIGR Whole Genome Shotgun Sequencing shotgunshotgun sequencesequence Warner Brothers, Inc.Warner Brothers, Inc.
    7. 7. TIGRTIGR Assemble Fragments sequencer outputsequencer output assembleassemble fragmentsfragments Closure &Closure & AnnotationAnnotation
    8. 8. TIGRTIGR General Steps in 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
    9. 9. TIGRTIGR Comparative Genomics • Comparison of genomes between species • Identify differences – SNPs – Indels – Rearrangements – Presence/absence of genes, pathways, features • Correlating with phenotypic differences • Can be used to improve on every step in genome analysis
    10. 10. TIGRTIGR Comparative Genomic Hybridization of GroupB strep
    11. 11. TIGRTIGR Chromosome Duplications in Arabidospsis
    12. 12. TIGRTIGR 100s of DNA Islands in O157:H7 vs. K12: Gene Loss or Transfer? from Eisen (2001)
    13. 13. TIGRTIGRTIGRTIGR “Nothing in biology makes sense except in the light of evolution.” T. H. Dobzhansky (1973)
    14. 14. TIGRTIGR Evolution and Genomics Overlap • Genome sequences contain a record of the evolution of a species and all its genes • Evolutionary analysis is the key to interpreting genome sequences and making the most use out of them
    15. 15. TIGRTIGR Phylogenomics? Evolutionary information improves genome analysis -Classification of multigene families -Predicting functions -Origins of genes and pathways Genomics information improves evolutionary reconstructions -More sequences of genes -Unbiased sampling -Presence/absence needed to infer certain events Feedback loop between two types of analysis TIGRTIGR
    16. 16. TIGRTIGR
    17. 17. TIGRTIGR Why Completeness is Important • Improves characterization of genome features – Gene order, replication origins • Better comparative genomics – Genome duplications, inversions • Determination of presence and absence of particular genes and features 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
    18. 18. TIGRTIGR Uses of Phylogenomics • Species evolution and systematics • Lateral versus vertical evolution • Gene function • Gene and genome duplications • Genome rearrangements
    19. 19. TIGRTIGR 0.1AcidobacteriaBacteroidesFibrobacteresGemmimonasVerrucomicrobiaPlanctomycetesChloroflexiProteobacteriaChlorobiFirmicutesFusobacteriaActinobacteriaCyanobacteriaChlamydiaSpriochaetesDeinococcus-ThermusAquificaeThermotogaeTM6OS-KTermite GroupOP8Marine GroupAWS3OP9NKB19OP3OP10TM7OP1OP11NitrospiraSynergistesDeferribacteresThermudesulfobacteriaChrysiogenetesThermomicrobiaDictyoglomusCoprothmermobacterThis projectPublishedIn progressUncultured lineageTree based on Hugenholtz (2002) with some modifications. Species Evolution I: Selecting Genome Projects to Increase Phylogenetic Diversity
    20. 20. TIGRTIGR Species EvolutionI I: Major Evolutionary Transitions • Analysis of S. pombe genome (Wood et al 2002) • Compared the genomes of eukaryotes to those of prokaryotes • Asked: “Are there genes in all eukaryotes with no obvious homologs in any prokaryote?” • Found ~200 genes which included many with know major roles in “eukaryotic” features like the cytoskeleton and chromatin as well as many with no known function
    21. 21. TIGRTIGR Bacteria Archaea Eukaryotes Giardia Trichomonas Naegleria Trypanosoma Euglena Plasmodium Tetrahymena Phytophthora Arabidopsis Chlamydomonas Dictyostelium Humans Fly Worm Encephalatozoon S. cerevisiae S. pombe Evolutionary Scenario
    22. 22. TIGRTIGR Evolutionary Transitions II: Single- vs. Multi-Cellularity • Analysis of S. pombe genome (Wood et al. 2002) • Compared multi-cellular vs. single-cellular species • Asked “Are there genes in all multi-cellular and not in any single-cellular?” • Found only 3 • Concluded that the multicellularity was likely the result of gene regulatory processes
    23. 23. TIGRTIGR Plants Giardia Trichomonas Parabisalia Diplomonads Naegleria Trypanosoma Euglena Plasmodium Tetrahymena Phytophthora Arabidopsis Chlamydomonas Fungi Animals Dictyostelium Humans Fly Worm Encephalatozoon S. cerevisiae S. pombe Microsporidia Dictyostelia Heterokonts Ciliates Apicomplexa Kinetoplastids Euglenas Acrasidae Multiple Origins of Multicellularity
    24. 24. TIGRTIGR Species Evolution III: Uncultured Microbes • Vast majority of microbes have never been cultured • Usually studied indirectly by cloning rRNA genes and using position within rRNA tree to predict biology • These predictions are frequently inaccurate
    25. 25. TIGRTIGR Genomics does not require initial culturing step. • Isolate, by filtration, all bacteria in a water sample • Extract total DNA in very large pieces • Clone those pieces as BACs into E.coli to get enough. • Sequence the BACs like a bacterial genome. Natural Water Filter concentrate Extract DNA Clone Into BACs Sequence Gene List
    26. 26. TIGRTIGR Phylogenetic Anchors Beja et al. 2000
    27. 27. TIGRTIGR Using a rRNA anchor allowed the identification of a new form of phototrophy: Proteorhodopsin Beja et al. 2000
    28. 28. TIGRTIGR Uses of Phylogenomics • Species evolution and systematics • Lateral versus vertical evolution • Gene function • Gene and genome duplications • Genome rearrangements
    29. 29. TIGRTIGR Vertical Inheritance From C. Darwin, origin of species, via W. F. Doolittle
    30. 30. TIGRTIGR Examples of Horizontal Transfers • Antibiotic resistance genes • Insertion sequences • Agrobacterium Ti plasmid • Toxin degradation genes on plasmids • Virus and phage gene acquisition and transfer • Organelle to nucleus transfers
    31. 31. TIGRTIGR Why Gene Transfers Are Useful to Identify • Laterally transferred genes frequently involved in environmental adaptations and/or pathogenicity • Identification of vectors of gene transfer (e.g., transposons, integrons, phage) • Identify species associations in the environment (e.g., Thermotoga and Archaea, Nelson et al.) • Identify organelle derived genomes in eukaryotic genomes
    32. 32. TIGRTIGR A Blast Search Does not Equal an Evolutionary Study
    33. 33. TIGRTIGR • Claim – “Hundreds of human genes appear likely to have resulted from horizontal transfer from bacteria at some point in the vertebrate lineage.” • Evidence – Genes match bacteria but not non-vertebrate eukaryotes – Or genes have stronger match to bacteria than to non-vertebrates
    34. 34. TIGRTIGR Implied Model for BVTs 1 2 3-6 Non Verts Vertebrates Protists Bacteria
    35. 35. TIGRTIGR Gene Loss? Inverts Vertebrates Protists Bacteria
    36. 36. TIGRTIGR Rate Variation? Inverts Vertebrates Protists Bacteria
    37. 37. TIGRTIGR Implied Model for BVTs 1 2 3-6 Non Verts Vertebrates Protists Bacteria
    38. 38. TIGRTIGR Number of pBVTs Depends on # of Genomes Analyzed 1 2 3 4 5 Other 0 200 400 600 800 1000 1200 1400 1600 1800 Number of protein sets Fruit fly C. elegans Arabidopsis Yeast Parasites Salzberg et al. 2001
    39. 39. TIGRTIGR Trees Don’t Support Transfer Paramecium bursaria Chlorella virus 1Homo sapiens HAS1Mus musculus HAS1Xenopus laevisXenopus laevisDanio rerioHomo sapiensMus musculusDanio rerioXenopus laevisGallus gallusBos taurusHomo sapiensMus musculusRattus norvegicusBradyrhizobium sp SNU001Rhizobium leguminosarumRhizobium spRhizobium lotiRhizobium tropiciRhizobium sp. NodCMesorhizobium sp 7653RSinorhizobium melilotiRhizobium melilotiRhizobium leguminosarumRhizobium galegaeAzorhizobium caulinodansStigmatella aurantiacaStreptomyces coelicolorStreptococcus uberisStreptococcus equisimilisStreptococcus pyogenes HASAStreptococcus pneumoniae0.2 BacteriaVertebratesVirusIIIIII Salzberg et al. 2001
    40. 40. TIGRTIGR Trees Don’t Support Transfer II
    41. 41. TIGRTIGR Organellar to Nuclear Transfers in A. thaliana
    42. 42. TIGRTIGR Organelle to Nucleus Transfer are Common From W. F. Doolittle
    43. 43. TIGRTIGR
    44. 44. TIGRTIGR Mitochondrial Genome Integration into A. thaliana chrII 3.2E+063.3E+063.4E+063.5E+063.6E+06D’1 A. thaliana Mitochondrial Alternative Genome Possible Insertion Point 3 D’1A’3C1B3B.C.D.Chromosome II1E+052E+053E+054E+05Alternative Mitochondrial Form03CBA’
    46. 46. TIGRTIGR SYNSP0100200300400500600700800900 Number of Best Matches to This Species050010001500200025003000350040004500 Number of ORFs in Complete Genome Best Matches vs. Prokaryotes
    47. 47. TIGRTIGR SYNSP0100200300400500600700800900 Number of Best Matches to This Species050010001500200025003000350040004500 Number of ORFs in Complete Genome Best Matches vs. Prokaryotes
    48. 48. TIGRTIGR Blast Phylogeny≠ 231456
    50. 50. TIGRTIGR Uses of Phylogenomics • Species evolution and systematics • Lateral versus vertical evolution • Gene function • Gene and genome duplications • Genome rearrangements
    51. 51. TIGRTIGR Predicting Function • Identification of motifs – Short regions of sequence similarity that are indicative of general activity – e.g., ATP binding • Homology/similarity based methods – Gene sequence is searched against a databases of other sequences – If significant similar genes are found, their functional information is used • Problem – Genes frequently have similarity to hundreds of motifs and multiple genes, not all with the same function TIGRTIGR
    53. 53. TIGRTIGR Blast Search of H. pylori “MutS” Score E Sequences producing significant alignments: (bits) Value sp|P73625|MUTS_SYNY3 DNA MISMATCH REPAIR PROTEIN 117 3e-25 sp|P74926|MUTS_THEMA DNA MISMATCH REPAIR PROTEIN 69 1e-10 sp|P44834|MUTS_HAEIN DNA MISMATCH REPAIR PROTEIN 64 3e-09 sp|P10339|MUTS_SALTY DNA MISMATCH REPAIR PROTEIN 62 2e-08 sp|O66652|MUTS_AQUAE DNA MISMATCH REPAIR PROTEIN 57 4e-07 sp|P23909|MUTS_ECOLI DNA MISMATCH REPAIR PROTEIN 57 4e-07 • Blast search pulls up Syn. sp MutS#2 with much higher p value than other MutS homologs
    54. 54. TIGRTIGR
    55. 55. TIGRTIGR H. pylori and MutS • Prior to this genome, all species that encoded a MutS homolog also encoded a MutL homolog • Experimental studies have shown MutS and MutL always work together in mismatch repair • Problem: what do we conclude about H. pylori mismatch repair
    56. 56. TIGRTIGR Table 3. Presence of MutS Homologs in Complete Genomes Sequences Species # of MutS Homologs Bacteria Escherichia coli K12 1 Haemophilus influenzae Rd KW20 1 Neisseria gonorrhoeae 1 Helicobacter pylori 26695 1 Mycoplasma genitalium G-37 0 Mycoplasma pneumoniae M129 0 Bacillus subtilis 169 2 Streptococcus pyogenes 2 Synechocystis sp. PCC6803 2 Treponema pallidum Nichols 1 Borrelia burgdorferi B31 2 Aquifex aeolicus 2 Deinococcus radiodurans R1 2 Archaea Archaeoglobus fulgidus VC-16, DSM4304 0 Methanococcus janasscii DSM 2661 0 Methanobacterium thermoautotrophicum ∆Η 1 Ευκαρψοτεσ Σαχχηαροµψχεσχερεϖισιαε 6 Ηοµο σαπιενσ 5
    58. 58. TIGRTIGR Phylogenetic Tree of MutS Family 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 StrpyBacsu Celeg Human Yeast MetthBorbu Aquae Synsp Deira Helpy mSaco Yeast Celeg Human
    59. 59. TIGRTIGR MutS Subfamilies 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 StrpyBacsu Celeg Human Yeast MetthBorbu Aquae Synsp Deira Helpy mSaco Yeast Celeg Human MSH4 MSH5 MutS2 MutS1 MSH1 MSH3 MSH6 MSH2
    60. 60. TIGRTIGR MutS Subfamilies • MutS1 Bacterial MMR • MSH1 Euk - mitochondrial MMR • MSH2 Euk - all MMR in nucleus • MSH3 Euk - loop MMR in nucleus • MSH6 Euk - base:base MMR in nucleus • MutS2 Bacterial - function unknown • MSH4 Euk - meiotic crossing-over • MSH5 Euk - meiotic crossing-over
    61. 61. TIGRTIGR Overlaying Functions onto Tree Aquae Trepa Rat Fly Xenla Mouse Human Yeast Neucr Arath Borbu Synsp Neigo Thema Strpy Bacsu Ecoli TheaqDeira Chltr Spombe Yeast Yeast Spombe Mouse Human Arath Yeast Human Mouse Arath StrpyBacsu Human Celeg Yeast MetthBorbu Aquae Synsp Deira Helpy mSaco Yeast Celeg Human MSH4 MSH5 MutS2 MutS1 MSH1 MSH3 MSH6 MSH2
    62. 62. TIGRTIGR Functional Prediction Using Tree 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 MSH1 Mitochondrial Repair MSH3 - Nuclear RepairOf Loops MSH6 - Nuclear Repair Of Mismatches MutS1 - Bacterial Mismatch and Loop Repair StrpyBacsu Celeg Human Yeast MetthBorbu Aquae Synsp Deira Helpy mSaco Yeast Celeg Human MSH4 - Meiotic Crossing Over MSH5 - Meiotic Crossing Over MutS2 - Unknown Functions MSH2 - Eukaryotic Nuclear Mismatch and Loop Repair
    63. 63. TIGRTIGR
    64. 64. TIGRTIGR Table 3. Presence of MutS Homologs in Complete Genomes Sequences Species # of MutS Homologs Which Subfamilies? MutL Homologs Bacteria Escherichia coli K12 1 MutS1 1 Haemophilus influenzae Rd KW20 1 MutS1 1 Neisseria gonorrhoeae 1 MutS1 1 Helicobacter pylori 26695 1 MutS2 - Mycoplasma genitalium G-37 - - - Mycoplasma pneumoniae M129 - - - Bacillus subtilis 169 2 MutS1,MutS2 1 Streptococcus pyogenes 2 MutS1,MutS2 1 Mycobacterium tuberculosis - - - Synechocystis sp. PCC6803 2 MutS1,MutS2 1 Treponema pallidum Nichols 1 MutS1 1 Borrelia burgdorferi B31 2 MutS1,MutS2 1 Aquifex aeolicus 2 MutS1,MutS2 1 Deinococcus radiodurans R1 2 MutS1,MutS2 1 Archaea Archaeoglobus fulgidus VC-16, DSM4304 - - - Methanococcus janasscii DSM 2661 - - - Methanobacterium thermoautotrophicum ∆Η 1 ΜυτΣ2 − Ευκαρψοτεσ Σαχχηαροµψχεσχερεϖισιαε 6 ΜΣΗ1−6 3+ Ηοµο σαπιενσ 5 ΜΣΗ2−6 3+
    65. 65. TIGRTIGR
    67. 67. TIGRTIGR rRNA and Uncultured Microbes
    68. 68. 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
    69. 69. TIGRTIGR Arabidopsis thalianaGP9651815g Drosophila melanogasterGP72929 Homo sapiensSPP49917DNL4 HUMAN Gallus gallusGP15778121dbjBAB6 Xenopus laevisGP18029886gbAAL5 Candida albicansSPP52496DNLI C Saccharomyces cerevisiaeGP1151 Schizosaccharomyces pombeGP700 Camelpox virusGP18483081gbAAL7 Variola major virusGP439074gbA Cowpox virusGP20153167gbAAM136 Vaccinia virusGP2772802gbAAB96 VIRUS vaccinia 9791118refNP 06 Vaccinia virus strain Tian Tan Monkeypox virusGP17529940gbAAL Homo sapiensSPP49916DNL3 HUMAN Mus musculusGP1794221gbAAC5300 Xenopus laevisGP18029884gbAAL5 lumpy skin disease virusGP1514 Swinepox virusGP18448623gbAAL6 Myxoma virusGP6523988gbAAF1502 Rabbit fibroma virusGP392838gb Fowlpox virusGP453602embCAA828 Drosophila melanogasterGP72996 Arabidopsis thalianaSPQ42572DN Oryza sativaGP16905197gbAAL310 Crithidia fasciculataGP312384e Caenorhabditis elegansSPQ27474 Drosophila melanogasterGP72916 Homo sapiensSPP18858DNL1 HUMAN Mus musculusSPP37913DNL1 MOUSE Rattus norvecusSPQ9JHY8DNL1 RA Xenopus laevisSPP51892DNL1 XEN Plasmodium falciparumGP1815859 Schizosaccharomyces pombeSPP12 Saccharomyces cerevisiaeSPP048 Aeropyrum pernixSPQ9YD18DNLI A Acidianus ambivalensSPQ02093DN Sulfolobus solfataricusSPQ980T Sulfolobus shibataeSPQ9P9K9DNL Sulfolobus tokodaiiSPQ976G4DNL Aquifex aeolicusGP2983805gbAAC Aquifex aeolicusSPO67398DNLI A Pyrobaculum aerophilumGP409906 uncultured crenarchaeote 74A4G Thermoplasma acidophilumSPQ9HJ Thermoplasma volcaniumOMNINTL0 Methanosarcina acetivorans str Archaeoglobus fuldusSPO29632DN A METAC 19916535gbAAM05952.1 D Pyrococcus abyssiSPQ9V185DNLI Pyrococcus horikoshiiSPO59288D Pyrococcus furiosusSPP56709DNL Thermococcus kodakaraensisGP10 Thermococcus fumicolansSPQ9HH0 Methanopyrus kandleri AV19GP19 Methanococcus jannaschiiSPQ576 Halobacterium sp.SPQ9HR35DNLI Streptomyces coelicolorSPQ9FCB Lymantria dispar nucleopolyhed Ligase IV Viral ligases Ligase I Archaeal Ligase DNA Ligase Tree
    70. 70. TIGRTIGR Problems with Similarity Based Functional Prediction • Prone to database error propagation. • Cannot identify orthologous groups reliably. • Perform poorly in cases of evolutionary rate variation and non-hierarchical trees (similarity will not reflect evolutionary relationships in these cases) • May be misled by modular proteins or large insertion/deletion events. • Are not set up to deal with expanding data sets. TIGRTIGR
    71. 71. TIGRTIGR Evolutionary Rate Variation 231456
    72. 72. TIGRTIGR Rate Variation and Duplication Species 3Species 1Species 21A2A3A1B2B3BDuplication
    73. 73. TIGRTIGR 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. radioAlkA Gram+AlkA E. coliMGMT Euks Alkylation Repair Genes
    74. 74. TIGRTIGR Clustering vs. Neighbor-joining MutS2.SynsMutS2.BacsMutS2.HelpMutS2.DeirMutsl.MettMSH4.CelegMSH4.YeastMSH4.humanmMutS.SacoMSH3.yeastC23C11.SpoMSH1.YeastMSH3.HumanREP1.MouseGTBP.MouseGTBP.HumanMSH6.YeastMSH5.HumanMSH5.CelegMSH5.YeastMSH2.HumanMSH2.MouseMSH2.YeastMutS.EcoliMutS.SynspMutS.DeiraMutS.Bacsu MutS.EcoliMutS.SynspMutS.BacsuMutS.DeiraMSH2.HumanMSH2.MouseMSH2.YeastMSH3.HumanREP1.MouseGTBP.MouseGTBP.HumanMSH6.YeastC23C11.SpoMSH1.YeastMSH3.yeastMSH4.CelegMSH4.humanMSH5.CelegMSH5.YeastmMutS.SacoMSH5.HumanMSH4.YeastMutS2.SynsMutS2.BacsMutS2.DeirMutS2.HelpMutsl.Mett UPGMANeighbor-Joining
    75. 75. TIGRTIGR Types of Molecular Homology • Homologs: genes that are descended from a common ancestor (e.g., all globins) • Orthologs: homologs that have diverged after speciation events (e.g., human and chimp β-globins) • Paralogs: homologs that have diverged after gene duplication events (e.g., α and β globin). • Xenologs: homologs that have diverged after lateral transfer events • Positional homology: common ancestry of specific amino acid or nucleotide positions in different genes
    76. 76. TIGRTIGR Caution: Homology Based Predictions Have Many Flaws • Not all orthologs have the same function • Homology cannot be used to characterize novel pathways (e.g., D. radiodurans) • Absence of genes can be important to phenotypes (e.g., pathogenicity)
    77. 77. TIGRTIGR Deinococcus radiodurans
    78. 78. TIGRTIGR DNA Repair Genes in D. radiodurans Complete Genome Process Genes in D. radiodurans Nucleotide Excision Repair UvrABCD, UvrA2 Base Excision Repair AlkA, Ung, Ung2, GT, MutM, MutY-Nths, MPG AP Endonuclease Xth Mismatch Excision Repair MutS, MutL Recombination Initiation Recombinase Migration and resolution RecFJNRQ, SbcCD, RecD RecA RuvABC, RecG Replication PolA, PolC, PolX, phage Pol Ligation DnlJ dNTP pools, cleanup MutTs, RRase Other LexA, RadA, HepA, UVDE, MutS2
    79. 79. TIGRTIGR Recombination Genes in Genomes Pathway |------------------------------Bacteria---------------------------| |---Archaea---| Euks Protein Name(s) Initiation RecBCD pathway RecB + + - - - - - - + + - + - - - - - - - - RecC + + - - - - - - + ±+ - ± - - - - - - - - RecD + + - - ± - - - + ±+ - ++ - ± ±+ - - - - - RecF pathway RecF + + + - + - - + + - + ± - - + - - ± ± ± RecJ + + + + + - - + - + + + + + + - - - - - RecO + + - - + - - + + - - - - - ± - - - - - RecR + + + ±+ + - - + + - + + - + + - - - - - RecN + + + + + - - + + - + - ± + + - - ± ± - RecQ + + - - + - - + - - + - - - + - - - - + ++ RecE pathway RecE/ExoVIII + - - - - - - - - - - - - - - - - - - - RecT + - - - + - - - - - - - - - - - - - - - SbcBCD pathway SbcB/ExoI + + - - - - - - - - - - - - - - - - - - SbcC + - - - + - - + - + + - + + + ± ± ± ± ± ± SbcD + - - - + - - + - + + - + + + ± ± ± ± ± ± AddAB Pathway AddA/RexA - - + - + - - - - - + + - ± - - - - - - AddB/RexB - - - - + - - - - - - - - - - - - - - - Rad52 pathway Rad52, Rad59 - - - - - - - - - - - - - - - - - - - ++ + Mre11/Rad32 ± - - - ± - - ± - ± ± - ± ± ± + + + + + + Rad50 ± - - - ± - - ± - ± ± - ± ± ± + + + ± + + Recombinase RecA, Rad51 + + + + + + + + + + + + + + + + + + + ++ ++ Branch migration RuvA + + + + + + + + + + + + + - + - - - - - RuvB + + + + + + + + + + + + + - + - - - - - RecG + + + + + - - + + + + - + + + - - - - - Resolvases RuvC + + + + - - - + + - + + + - + - - - - - RecG + + + + + - - + + + + - + + + - - - - - Rus + - - - - - - - ±+ - - - - ±+ - - - - - - CCE1 - - - - - - - - - - - - - - - - - - - + Other recombination proteins Rad54 - - - - - - - - - - - - - - - - - - - + + Rad55 - - - - - - - - - - - - - - - - - - - + + Rad57 - - - - - - - - - - - - - - - - - - - + + Xrs2 - - - - - - - - - - - - - - - - - - - +
    80. 80. TIGRTIGR Unusual Features of D. radiodurans DNA Repair Genes Process Genes Nucleotide excision repair Two UvrAs Base excision repair Four MutY-Nths Recombination RecD but not RecBC Replication Four Pol genes dNTP pools Many MutTs, two RRases Other UVDE
    81. 81. TIGRTIGR Problem: List of DNA repair gene homologs in D. radiodurans genome is not significantly different from other bacterial genomes of the similar size
    82. 82. TIGRTIGR Repair Studies in Different Species (determined by Medline searches as of 1998) Humans 7028 E. coli 3926 S. cerevisiae 988 Drosophila 387 B. subtilits 284 S. pombe 116 Xenopus 56 C. elegans 25 A. thaliana 20 Methanogens 16 Haloferax 5 Giardia 0
    83. 83. TIGRTIGR -Ogt -RecFRQN -RuvC -Dut -SMS -PhrI -AlkA -Nfo -Vsr -SbcCD -LexA -UmuC -PhrI -PhrII -AlkA -Fpg -Nfo -MutLS -RecFORQ -SbcCD -LexA -UmuC -TagI -PhrI -Ogt -AlkA -Xth -MutLS -RecFJORQN -Mfd -SbcCD -RecG -Dut -PriA -LexA -SMS -MutT -PhrI -PhrII? -AlkA -Fpg -Nfo -RecO -LexA -UmuC -PhrI -Ung? -MutLS -RecQ? -Dut -UmuC -PhrII -Ogg -Ogt -AlkA -TagI -Nfo -Rec -SbcCD -LexA -Ogt -AlkA -Nfo -RecQ -SbcD? -Lon -LexA -AlkA -Xth -Rad25? -AlkA -Rad25 -Nfo -Ogt -Ung -Nfo -Dut -Lon -Ung -PhrII -PhrI Ecoli Haein Neigo Helpy Bacsu Strpy Mycge Mycpn Borbu Trepa Synsp Metjn Arcfu Metth Human Yeast BACTERIA ARCHAEA EUKARYOTES from mitochondria +Ada +MutH +SbcB dPhr +TagI? +Fpg +UvrABCD +Mfd +RecFJNOR +RuvABC +RecG +LigI +LexA +SSB +PriA +Dut? +Rus +UmuD +Nei? +RecE tRecT? +Vsr +RecBCD? +RFAs +TFIIH +Rad4,10,14,16,23,26 +CSA +Rad52,53,54 +DNA-PK, Ku dSNF2 dMutS dMutL dRecA +Rad1 +Rad2 +Rad25? +Ogg +LigII +Ung? +SSB, +Dut? +PhrI, PhrII +Ogt +Ung, AlkA, MutY-Nth +AlkA +Xth, Nfo? +MutLS? +SbcCD +RecA +UmuC +MutT +Lon dMutSI/MutSII dRecA/SMS dPhrI/PhrII +Spr t3MG +Rad7 +CCE1 +P53 dRecQ dRad23 +MAG? -PhrII -RuvC tRad25 +TagI? +RecT tUvrABCD tTagI ? Gain and Loss of Repair Genes TIGRTIGR
    84. 84. TIGRTIGR Functional and Evolution III: Non-Homology Based Analysis
    85. 85. TIGRTIGR Non Homology Based Functional Prediction: Phylogenetic Profiles
    86. 86. TIGRTIGR
    87. 87. TIGRTIGR Phylogenetic Profile - E.coli Flagellar GenesfhiAfliMfliPfliGflgGfliFflgIflhAflhBgcpE Wu and Eisen, unpublished
    88. 88. 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)
    89. 89. TIGRTIGR Phylogenetic Profile - C. tepidum Chlorophyll Synthesis Wu and Eisen, unpublished 5002_cobalamin biosynthesis protein CbiG/precorrin-4 C11-methyltransferase3939_precorrin-3B C17-methyltransferase/precorrin-8X methylmutase cbiJH882_cobyric acid synthase cbiP3160_dsrN protein dsrN862_cobyrinic acid a,c-diamide synthase cbiA-14010_cobN protein, putative2641_magnesium-protoporphyrin methyltransferase bchH-31498_magnesium-protoporphyrin methyltransferase bchH-14003_cobN protein, putative2636_magnesium-protoporphyrin methyltransferase bchH-24008_magnesium-chelatase, subunit I chlI-24007_magnesium-chelatase, subunit D/I family1504_magnesium-chelatase, subunit I chlI-1
    90. 90. TIGRTIGR C. tepidum encodes a novel RbcL Chlorobium tepidum ORF02314 Pseu domo nas hydro genot herm ophi Archaeoglobus fulgidus gi2648975 Bacillus subtilis gi2633730 Methanococcus jannaschii gi2129276 Pyrococcus abysii gi|5458634 Pyrococcus horikoshii gi|3257353 Pyr ococcus karaensis gi3769302 Achaeoglobus fulgidus gi2648911 0.005 changesIV Rhodobacter capsulatus2522275Rhodobacter sphaeroides1 15192Alcaligenes eutrophusRalstonia eutropha3377785Alcaligenes eutrophus 950106Xanthobacter flavus 48544Galdieria partita 4519903Galdieria partitaGaldieria sulphuraria 8925949Cyanidium caldariumCyanidioschyzon merolaeGephyrocapsa oceanicaEmiliania huxleyiPleurochrysis carteraePleurochrysis carterae 456606Calyptrosphaera sphaeroideaUmbilicosphaera sibogaeChrysochromulina hirtaPavlova salinaPorphyridium aerugineumGelidiella acerosaSpermothamnion repensEupogodon planusCeramium diaphanumAntithamnion sp.Sarcodia ceylanicaPterocladia lucidaGelidium sesquipedale 3581614Gelidium americanumGelidium elegans 7107687Gelidium pusillum 392980Capreolia implexaCallophyllis violaceaOnikusa japonicumYatabella hirsutaAcanthopeltis japonicaPterocladiella capillaceaPtilophora pinnatifidaPortieria japonicaGracilariopsis sp.Eucheuma isiforme 4323441Agardhiella ramosissimaMeristotheca papulosaEucheuma arnoldiiKappaphycus alvareziiBetaphycus philippinensisSolieria chordalisMastocarpus stellatusRhodogorgon carriebowensisHeringia mirabilisAhnfeltiopsis gigartinoidesCaulacanthus ustulatusAreschougia congestaCallophycus africanusErythroclonium angustatumHypnea charoidesRhabdonia clavigeraMastocarpus papillatus 450801Sarcothalia livida 5020070Gigartina skottsbergii 5020042Iridaea cordataIridaea cordata 5020044Mazzaella californicaChondrus nipponicus 5020030Chondrus pinnulatus 5020034Chondrus yendoi 5020036Chondrus canaliculatusTrematocarpus dichotomusTrematocarpus dichotomus 96154Chondracanthus chamissoi 50200Chondracanthus acicularisChondracanthus tenellus 502002Gigartina radula 5020040Amphiroa fragilissimaPorphyra purpurea cpst 1276692Cryptomonas cpst 3602978Aureoumbra lagunensisAureococcus anophagefferensOlisthodiscus luteus cpst 1192Tetrasporopsis fuscescens 6006Tetrasporopsis fuscescensPhaeothamnion confervicolaPhaeoschizochlamys mucosaTurbinaria ornataIsthmoplea sphaerophoraPogotrichum filiformeCoelocladia arcticaRosenvingea intricataHydroclathrus clathratusChnoospora implexaColpomenia sinuosaScytosiphon lomentariaPilayella littoralisDelamarea attenuataDictyosiphon foeniculaceusHecatonema sp.Elachista fucicolaPunctaria plantagineaPetalonia binghamiaeStictyosiphon soriferusStriaria attenuataLitosiphon pusillusLaminariocolax tomentosoidesMyriotrichia clavaeformisSorocarpus micromorusStreblonema tenuissimumMyrionema strangulansGiraudia sphacelarioidesHummia onustaMischococcus sphaerocephalusBotrydium stoloniferumXanthonema debileTribonema aequaleVaucheria bursataPleurochloridella botrydiopsisPseudopedinella elasticaPhaeodactylum tricornutumRhizosolenia setigeraDetonula confervaceaThalassiosira nordenskioeldiiOdontella sinensisUnidentified diatom endosymbioCylindrotheca sp.MnBradyrhizobium japonicum 41605 II ChlorellaChloromonas sp. ANT1Mesostigma viride 7259514AgmenellumProchlorothrix hollandic 45543Anabaena sp.Anabaena sp.Anabaena sp.142086Astasia longaEuglena gracilisSpirotaenia condensata 1145421Gonatozygon monotaeniumGenicularia spirotaeniaLycopodium clavatumLycopodiella alopecuroidesPhylloglossum drummondiiHuperzia campianaTrichomanes alatumSelaginella bombycinaSelaginella sp. 577150Botrypus strictusIsoetes melanopoda 577149Isoetes lacustrisAngiopteris lygodiifoliaElaphoglossum yoshinagaeBlechnum occidentaleAdiantum capillusvenerisMarsilea ancylopodaCyathea sp. Wolf 1994Hymenophyllopsis dejectaMatonia foxworthyiLophosoria quadripinnataOsmunda cinnamomeaDennstaedtia sp. Wolf 623Polypodium vulgareHypolepis sp. Wolf 628Polypodiodes formosanaGoniophlebium persicifoliumPhanerosorus majorSalvinia cucullata 515459Coleochaete nitellarumKlebsormidium sp. 552613Anthoceros formosae cp 1389564Lathyrus tuberosusCoronilla emerusPersicaria hydropiperAchlys triphyllaHibiscus punaluuensisMontinia caryophyllaceaHernandia albifloraAlangium chinenseCleome hasslerianaCitrus x paradisiFortunella japonicaStyrax japonicaWisteria sp.Ladenbergia pavoniiPolypremum procumbensBrodiaea coronariaDichelostemma multiflorumMedicago sativaPhiladelphus lewisiiAextoxicon punctatumPittosporum japonicumManglietia fordianaBerberis thunbergiiOphiocolea floribundaViburnum rhytidophyllumAucuba japonicaBulbinella caudafelisKniphofia uvariaAstelia banksiiCentrolepis strigosaEmpodium veratrifoliumCurculigo capitulataZingiber gramineumCalathea loeseneriStrelitzia nicolaiNephrophyllidium cristagalliAcicarpha tribuloidesKalanchoe daigremontianaOpercularia vaginataCalycophyllum candidissimumPhyllis noblaHippuris vulgarisDigitalis purpureaLathraea clandestinaAlectra orobanchoidesNemum spadiceumBulbostylis atrosanguineaFimbristylis complanatacyperus rigidifoliusKyllinga appendiculataPycreus flavescensLipocarpha microcephalaAscolepis capensisHarveya capensisCallitriche albomarginataMyriophyllum exalbescensPenthorum sedoidesTetracarpaea tasmanicaTetracarpaea tasmanica 7240484Geniostoma rupestreArceuthobium verticilliflorumGinalloa arnottianaConnarus conchocarpusPhysena sp.Apeiba tibourbouLasiopetalum sp. Chase 2195Didymosalpinx noraeTrigonia niveaMachaerium lunatumHolocalyx balansaeColona floribundaDalbergia hupeanaHugonia platysepalaMaackia amurensisCapparis hastataEuchresta horsfieldiiParkia roxburghiiGlycyrrhiza echinataCalpurnia aureaBolusanthus speciosusBrongniartia pacificaAteleia herbertsmithiiAdesmia exilisSarcocephalus latifoliusTrichocarya splendensCochlospermum intermediumReevesia thyrsoideaGonystylus macrophyllusMytilaria laosensisAdenium obesumNerium oleanderUvularia floridanaArthropodium cirratumElegia cuspidataCleistes divaricataChysis bractescensGyrocarpus sp. Chase 317Croomia heterosepalaHerreria montevidenseWitsenia mauraBarbacenia elegansAriopsis peltataComospermum yedoenseXanthosoma mafaffaNolina recurvataEichhornia azureaPontederia cordataPeltandra virginicaNeuwiedia veratrifoliaIsotria verticillataSymplocarpus foetidusEleutherine latifoliaClivia miniataThomasia solanaceaEriaxis rigidaQuisqualis indicaRauvolfia manniiTerminalia catappaRhexia virginicaAmpelocera hottleyiDissotis rotundifoliaStylogyne sp.Primula sieboldiiZanthoxylum monophyllumAbrus precatoriusCordyla africanaCeriops australisBauhinia candicansNauclea orientalisCasuarina cunninghaminaHillia trifloraSisyndite sparteaNeoluederitzia sericeocarpaThevetia peruvianaUlex europaeusCassia didymobotryaSalweenia wardiiDelonix regiaClitoria ternateaParkinsonia aculeataRhopalocarpus sp.Simarouba glaucaKelleronia revoiliiTribulus macropterusKallstroemia maximaTribulopis pentandraCeratonia siliquaPintoa chilensisSericodes greggiiRobinia pseudoacaciaGoethalsia meianthaDimocarpus longanRhizophora apiculataLeptonychia pallidaGuaiacum guatemalensePicralima nitidaBalanites maughamiiOpilia amentaceaDiegodendron humbertiiCadia purpureaLuetzelburgia sp. Pennington sHydrangea macrophyllaAugea capensisZygophyllum billardierei 66896Zygophyllum hirticaule 6689634Fagonia creticaEustoma russellianumZygophyllum albumMacrolobium acaciifoliumZygophyllum coccineum 6689622Pterospermum celebicum 4995777Pterospermum celebicumGymnocladus dioicaAcacia caveniaPorlieria chilensisGleditsia triacanthosGrewia occidentalisHeliocarpus americanusPavonia multifloraWrightia arboreaStephanostema stenocarpumHildegardia barteriSchoutenia glomerataCola nitidaPentaplaris doroteaeBerrya javanicaChorisia speciosaCecropia palmataMascarenhasia arborescensCalopogon tuberosusGloriosa superbaLarrea cuneifoliaThespesia populneaArgania spinosaDirachma socotranaSchlumbergera truncataSecuridaca diversifoliaAbroma angustaDionaea muscipulaStylidium calcaratumOreostylidium subulatumKeraudrenia hermanniifoliaSetchellanthus caeruleusHallea rubrostipulataSenna alataLeitneria floridanaLiparia splendensPachysandra procumbensTrema micranthaHelicteres baruensisSophora bhutanicaXanthocercis zambesiacaStrumpfia maritimaCyclopia genistoidesPodalyria bifloraHedysarum vicioidesCaesalpinia pulcherrimaCephalanthus natalensisBlepharocarya depauperataAndrosace spinuliferaChorizema cordatumViscainoa geniculataThottea tomentosaSimaba bidwilliiHovea ellipticaAcosmium dasycarpumTamarindus indicaTipularia discolorAntirhea lucidaSimmondsia chinensisLabordia tinifoliaEuclea natalensisTriplaris americanaTetraena mongolicaBulnesia arboreaTriplochiton zambesiacusLespedeza cuneataArachis hypogaeaBursera inaguensisCommiphora habessinicaAllamanda catharticaMimosa speggazziniiTimonius sp. Ridsdale 2204Eremocitrus glaucaSeverinia buxifoliaAtalantia ceylanicaMicrocos latistipulataPleiospermium alatumTachigali paniculataHumiria balsaminiferaBunchosia armeniacaChaetachme aristataMetternichia princepsGironniera subaequalisPeltophorum sp. 2343002Prostanthera niveaBerchemia discolorVitex agnuscastusBaphia massaiensisErythrophleum ivorensePericopsis moonianaMorkillia mexicanaBrucea mollisAmaroria soulameoidesStachys macranthaMarrubium incanumRuttya fruticosaCaryopteris bicolorThymus alsinoidesOriganum laevigatumSalvia aethiopisPerovskia abrotanoidesRosmarinus officinalisCuscuta reflexaMonarda didymaMentha longifoliaGlechoma hederaceaVigna radiataRhachicallis americanaBixa orellanaSaccifolium bandeiraeJusticia odoraDipteryx odorataCyclonema myricoidesSterculia apetalaLeucophyllum frutescensBruguiera gymnorhizaDiospyros whyteana 1834444Westringia rosmariniformisAgastache foeniculumTectona grandisPeltophorum peltatumLuxemburgia ciliosaCybistax donnellsmithiiCrypteronia paniculataJacaranda sparreiScutellaria alpinaGenipa americanaMouriri helleriMapouria umbrosaRutidea orientalisPouchetia gilletiiSimira viridifloraKraussia floribundaLeptactina platyphyllaAidia micranthaFeretia aeruginescensGlossostipula concinnaOxyanthus pyriformisTabernaemontana divaricataCydista aequinoctialisMassularia acuminataMitriostigma axillareCalochone redingiiPavetta abyssinicaCatesbaea spinosaBertiera brevifloraHymenocoleus hirsutusHirtella bicornisGardenia thunbergiaRamosmania rodriguesiiKailarsenia ochreataTarenna neurophyllaCasasia clusiifoliaCremaspora trifloraOchna serrulataPorterandia crosbyiMorinda citrifoliaNeurocalyx zeylanicusGlossocalyx longicuspisNemuaron vieillardiiBracteanthus glycycarpusSiparuna brasiliensisAdenia digitataSauvagesia calophyllumSanango sp. Bremer 3352Rapanea ferrugineaHalleria lucidaGomphostigma scoparioidesSeymeria pectinataPandorea jasminoidesTricalysia cryptocalyxCoffea arabicaParacoffea melanocarpaDichapetalum crassifoliumPalicourea lasiorrachisUsteria guineensisMacarisia emarginataCoptosapelta flavescensBonyunia minorAlstonia scholarisBlepharistemma membranifoliaVantanea guianensisMuntingia calaburaDichilus lebeckioidesOphiorrhiza mungosFagopyrum callianthumRumex acetosellaOxalis dilleniiSchwenckia laterifloraLinum perenneAngophora hispidaCalycanthus occidentalisBaeckea ramosissimaVahlia capensisRubia tinctorumCrucianella angustifoliaValantia muralisCruciata glabraAsperula laevigataPhopsis stylosaSherardia arvensisGalium elongatumStauntonia hexaphyllaSatyrium nepalenseSaruma henryiColeonema pulchellumImpatiens capensisCrassula marnieranaCanarium ovatumHaplomitrium hookeriDysosma versipellisBuddleja asiaticaRibes aureumSinopodophyllum hexandrumCornus alternifoliaAnthospermum herbaceumGratiola pilosaHumulus lupulusPodophyllum peltatumAdenandra unifloraDiphylleia cymosaDipteronia sinensisUlmus parvifoliaHemiptelea davidiiPinckneya pubensBongardia chrysogonumMelolobium microphyllumTorenia fournieriPteroceltis tatarinowiiTinnea zambesiacaIndigofera australisTapirira mexicanaAesculus paviaAcer saccharumCyrtocarpa proceraSpondias cythereaAbobra tenuifoliaChamaecrista fasciculataGlycine maxAstragalus sparsusPeriploca graecaHoya bellaAsclepias curassavicaApocynum cannabinumStapelia leendertziaeTylophora sylvaticaDicraspidia donnellsmithiiVitis aestivalisTephrosia grandifloraKummerowia stipulaceaZornia cantoniensisCampylotropis griffithiiSesbania sesbanPlocosperma buxifoliumPlocama pendulaPolygonum cuspidatumHedwigia ciliataFunaria hygrometricaUleastrum palmicolaOrthotrichum lyelliUlota obtusiusculaBryodixonia perichaetialisRhabdoweisia crenulataTayloria lingulataSplachnum sphaericumFelipponea esquiroliiClimacium dendroidesDozya japonicaPilotrichopsis dentataBartramia pomiformisLoeskeobryum cavifoliumAntitrichia formosanaDuthiella speciosissimaCtenidium molluscumPlatyhypnidium riparioides 623Platyhypnidium riparioidesRhynchostegium pallidifoliumTaiwanobryum speciosumIsopterygium vinealePterobryopsis orientalis var.Entodontopsis leucostegaStereophyllum radiculosumDesmotheca apiculataCardotiella quinquefariaDolichomitriopsis diversiformiEntodon myurusHerpetineuron toccoaeAnomodon abbreviatusHaplohymenium longinerveCyptodontopsis obtusifoliaOkamuraea hakoniensisRhytidiadelphus loreusPlagiothecium denticulatumHylocomium splendensRhytidiadelphus japonicus 9967Pleurozium schreberiPterobryon arbusculaPleuroziopsis ruthenicaTrachyloma indicumSciaromium tricostatumForsstroemia neckeroidesTomentypnum nitensDrepanocladus aduncusCalliergonella cuspidataHypnum lindbergii 6230584Hypnum lindbergiiBrachythecium rivulareHylocomiastrum pyrenaicumNeodolichomitra yunnanensisTaxiphyllum aomorienseMyuroclada maximowicziiWijkia hornschuchiiBrotherella henoniiHeterophyllium nematosumPylaisiadelpha tenuirostrisThuidium recognitumTrachypodopsis auriculataEumyurium sinicumLeucodon nipponicusCryphaea sinensisAbietinella abietinaPylaisiella intricataBoulaya mitteniiSchlotheimia tectaZygodon intermediusMiyabea fruticellaMacromitrium incurvifoliumMacrocoma tenuis subsp. sullivGroutiella apiculataVenturiella sinensisAulacopilum hodgkinsoniaePhyscomitrella patensPtychomitrium gardneriAmphidium lapponicumMnium cuspidatumSphagnum fallaxDrummondia prorepensEncalypta proceraPorella pinnataTolypella proliferaChara connivensLamprothamnium papulosumLychnothamnus barbatusJubula pennsylvanicaLeucobryum scabrumMetzgeria furcataCalypogeia muellerianaMakinoa crispataLophocolea heterophyllaHerbertus pensilisLepidozia reptansPetalophyllum ralfsiiFossombronia foveolataMonoclea gottscheiDumortiera hirsutaConocephalum conicumLunularia cruciataAsterella tenellaRicciocarpos natansMarchantia polymorphaSphaerocarpos texanusGeothallus tuberosaMougeotia sp.Mougeotia sp.Cylindrocystis sp. UTEX1925Bryopsis maximaChlorella ellipsoideaChlorella ellipsoidea cpst 285Synechococcus sp.SP P00880Synechococcus PCC6301 38927Synechococcus sp. 217137Synechocystis PCC6803Hydrogenovibrio marinus1 59956Acidithiobacillus ferrooxidansHalothiobacillus neapolitanusNitrobacter winogradskyi1 5230Nitrobacter winogradskyi2 5230Nitrobacter vulgaris 349304Thiobacillus intermedius K12 4Alvinoconcha hessleri sym 1546Chromatium vinosum1 516602Thiobacillus ferrooxidans2 297Thiobacillus denitrificans1Hydrogenophaga pseudoflavaHydrogenovibrio marinus2 59956Synechococcus sp. 1850939Chromatium vinosum2 804821Pisum sativum 3893097Pisum sativum cpstCeltis sinensis var. japonicaAphananthe asperaAilanthus altissimaRulingia sp. Chase 2196Koeberlinia spinosaRorippa amphibiaArabis stelleriCardamine flexuosaArmoracia rusticanaNasturtium officinaleReseda albaLepidium virginicumCapsella bursapastorisArabidopsis himalaicaNeobeckia aquaticaDistylium racemosumAnagyris foetidaAjuga chamaepitysIlex brevicuspisUncaria rhynchophyllaOnonis spinosaDaphniphyllum sp.Photinia fraseriMitchella repensIsopogon latifoliusTulipa kolpakowskianaCyanella hyacinthoidesWatsonia angustaFreesia albaPopulus deltoidesLepuropetalon spathulatumHamamelis mollisShaniodendron subaequaleTovaria pendulaLimnanthes douglasiiPiptanthus nepalensisDrosophyllum lusitanicumMillegrana radiolaPinguicula caeruleaErodium texanumOenothera elata subsp. hookeriSedum rubrotinctumJasminum suavissimumZelkova serrataCobaea scandensHeteropyxis natalensisParnassia fimbriataCamptotheca acuminataLeucadendron laureolumRhoiptelea chilianthaLuculia grandifoliaEschscholzia californicaEucryphia lucidaFouquieria columnarisCoris monspeliensisAltingia sp. RBGEViviania marifoliaPelargonium capitatumStylophorum diphyllumBeesia calthifoliaDicranostigma franchetianaAverrhoa carambolaAnopterus macleayanus 1922257Chrysolepis sempervirensDendromecon rigidumGrubbia tomentosaMacleaya cordataGlaucium flavumRhodoleia championiiSarcocaulon vanderietiaeGalax urceolataTicodendron incognitumHunnemannia fumariifoliaLambertia inermisDisanthus cercidifoliusAndrocymbium ciliolatumGunnera hamiltoniiCyclamen hederifoliumExbucklandia populneaCephalotus follicularisHeliamphora nutansRetzia capensisZaluzianskya katharinaeEmorya suaveolensHebenstretia dentataScrophularia sp. DePamphilis STozzia alpinaLloydia serotinaCycnium racemosumStriga asiaticaChelone obliquaCollinsia grandifloraHemiphragma heterophyllumCatharanthus roseusPlatystemon californicusTropaeolum majusMonsonia emarginataGeranium grandiflorumCliftonia monophyllaAmphianthus pusillusAlonsoa unilabiataNemesia strumosaAtherosperma moschatumSamolus valerandiDaucus carotaApium graveolensMorina coulteriana 2065207Levenhookia leptanthaForstera bidwilliiCortusa matthioliCortusa matthioli 1834405Hypecoum imberbeLogania vaginalisMitreola petiolataMitrasacme pilosaCastilleja linariifoliaAngelonia pubescensMalesherbia linearifoliaOrobanche corymbosaByblis linifloraKorthalsella lindsayiDendrophthora clavataPhoradendron serotinumRoridula gorgoniasVelleia paradoxaKopsia fruticosaKoelreuteria paniculataDonatia fascicularisCuttsia viburneaProtea repensPlacospermum coriaceumSarracenia flavaKingdonia unifloraDodecatheon meadiaSchoepfia schreberiDrypetes roxburghiiCasimiroa edulisLysimachia azoricaLunasia amaraDictamnus sp. M.W.Chase1820KCalodendrum capenseMelicope ternataPilocarpus pennatifoliusNotothixos subaureusBuxus sempervirensSarcomelicope simplicifoliaPhelline comosaClematepistephium smilacifoliuGovenia sp. Chase O146Erythrorchis altissimaStyppeiochloa gynoglossaCathaya argyrophyllaCarludovica palmataLasia spinosaPeliosanthes arisanensisApostasia stylidioidesZamioculcas zamiifoliaLiriope platyphyllaLudovia integrifoliaAnchomanes difformisIris ensataOphiopogon jaburanChlorophytum comosumLomandra longifoliaAnthurium scherzerianumTripladenia cunninghamiiPetermannia cirrosaSpathiphyllum clevelandiiTriphora trianthophoraScindapsus aureusBehnia reticulataTropidia sp. Chase O211Oubanguia alataMargaritaria tetracoccaEschweilera odoraLaurus nobilisCorythophora rimosaLecythis pranceiCareya arboreaPlanchonia validaCouratari tauariBertholletia excelsaAsteranthos brasiliensisCariniana legalisCouroupita guianensisBarringtonia asiaticaAllantoma lineataGustavia poeppigianaEcheandia sp.Vanilla africanaLitsea japonicaPogonia japonicaSelenipedium chicaMexipedium xerophyticumKibara rigidifoliaWilkiea huegelianaOuratea duparquetianaRipogonum elseyanumZygogynum sp. Qiu 90024Millettia japonicaBaloskion gracileDilomilis montanaPseudowintera colorataTasmannia insipidaCoelia tripteraTaxus chinensisNeocallitropsis araucarioidesMicrobiota decussataCupressus sempervirensZamia floridanaDiselma archeriWiddringtonia cedarbergensisPhyllocladus trichomanoidesMetasequoia glyptostroboidesLibocedrus plumosaCephalotaxus wilsonianaAmentotaxus argotaeniaThuja occidentalisJuniperus confertaChamaecyparis obtusaThujopsis dolabrataTetraclinis articulataCallitris rhomboideaPlatycladus orientalis flagellAraucaria angustifoliaAgathis moorei 1850530Agathis borneensisWollemia nobilisCedrus deodaraPseudolarix amabilisKeteleeria davidianaAbies fabriPinus balfourianaCalocedrus decurrensNyssa sylvaticaTaxodium distichumTsuga heterophyllaLarix deciduaPicea abiesDuckeodendron cestroidesMetroxylon vitienseViscum albumAlzatea verticillataSabia sp. Qiu 91025Magnolia grandifloraSpiraea x vanhoutteiPrunus emarginata533056Gladiolus guienziiAspidistra elatiorTricalistra ochreataTupistra albifloraOrthrosanthus polistachusVeratrum albumHymenanthera alpinaStewartia pseudocamelliaAkania bidwilliiDegeneria vitiensisBretschneidera sinensisRavenala madagascariensisRhynchocalyx lawsonioidesOncotheca balansaeGynotroches axillarisCapirona decorticansAndira inermisPellacalyx saccardiansSarcococca confusaBalanops vieillardiPotalia resiniferaGoetzia elegansPosoqueria latifoliaPouteria eerwahAngylocalyx brauniiManilkara zapotaBurckella oxycarpaMolongum laxumPicramnia polyanthaAcokanthera oblongifoliaMollinedia ovataMaesa myrsinoidesAegle marmelosEriostemon brevifoliusParaserianthes lophanthaGenista elataHardenbergia violaceaAlbizia julibrissinCercis canadensisExostema caribaeumCladrastis sikokianaGymnostoma webbianumRetama sphaerocarpaPithecellobium mexicanumNepenthes alataSpathelia excelsaIrvingbaileya sp. Plunkett 151Derris laxifloraApuleia leiocarpaCanavalia ensiformisGlycosmis pentaphyllaDiplolaena dampieriCalypso bulbosaEucommia ulmoidesThermopsis fabaceaChorilaena quercifoliaPhebalium woombyeOsbeckia stellataNymania capensisSwietenia macrophyllaLicania tomentosaBaptisia tinctoriaArgyrolobium harveyanumCaragana arborescensCipadessa bacciferaTambourissa tauTrichilia emeticaSchmardaea microphyllaAbrophyllum ornansClusia gundlachiiMauloutchia chapelieriPaphiopedilum bellatulumParinari sumatranaClausena excavataAmorpha fruticosaTheophrasta americanaMelastoma malabathricumTapura amazonicaHintonia latifloraPhragmipedium longifoliumNitraria retusaStemona japonicaAristea glaucaThysanotus spinigerLanaria lanataStreptopus lanceolatusChordifex amblycoleusSaropsis fastigiataGuringalia dimorphaAcion hookeriLepyrodia glaucaAlexgeorgea ganopodaLepidobolus chaetocephalusHarperia laterifloraDielsia stenostachyaMelanostachya ustulataCalorophus elongatusLoxocarya gigasTyrbastes glaucescensMeeboldina canaLeptocarpus tenaxKulinia eludensEmpodisma minusTaraxis grossaWinifredia solaChaetanthus aristatusTremulina tremulaEurychorda complanataSporadanthus tasmanicusDapsilanthus ramosusColeocarya gracilisDesmocladus castaneusBomarea hirtellaStawellia dimorphanthaSimethis mattiazziiPhormium tenaxStypandra glaucaNivenia corymbosaAmana edulisSparrmannia ricinocarpaProsartes lanuginosaXeronema callistemonRhodohypoxis milloidesSpirodela intermediaDisa tripetaloidesPersea americanaTorreya nuciferaHortonia floribundaIpheion dialystemonLeucocrinum montanumMedeola virginianaBorya septentrionalisWelwitschia mirabilisEphedra sinicaAloe bakeriHemerocallis fulvaJohnsonia pubescensAnemarrhena asphodeloidesBulbine succulentaPoellnitzia rubrifloraTrachyandra sp.Haworthia subfasciataLomatophyllum purpureumAstroloba foliosaEremurus himalaicusGasteria liliputianaAsphodeline luteaLimonium axillareSaharanthus ifniensisPsylliostachys suworowiiPlumbago auriculataLimoniastrum guyonianumArmeria splendensCeratolimon feeiDoryanthes excelsaIsophysis tasmanicaGeophila repensChassalia parvifloraVochysia hondurensisLachnocaulon ancepsOryza sativaHordeum jubatumPeridictyon sanctumLeymus chinensisEremium erianthumElytrophorus globularisAmphipogon strictusElymus glaucescensPseudoroegneria spicataZizania texanaAristida congesta subsp. barbiZea maysCyperochloa hirsutaBowiea volubilisAgapanthus africanusDasylirion serratifoliumCampylandra sp. Tamura and YamHuntleya heteroclitaCryptarrhena sp. Chase O307Dichaea riopalenquensisCalibanus hookeriTristagma bivalveMontrichardia arborescensPolianthes geminifloraKoellensteinia gramineaHosta rectifoliaTulbaghia violaceaXanthorrhoea hostilisMonochoria cyaneaZygopetalum intermediumPsychotria borucanaSchoenus nigricansFicinia gracilisBolboschoenus maritimusRhynchospora nervosaKyllingiella polyphyllaScirpus polystachyusCyperus dichroostachyusOxycaryum cubensePleurostachys sp. Kallunki etMesomelaena pseudostygiaGahnia javanicaSchoenoplectus articulatusAbildgaardia ovataFuirena ciliarisHellmuthia membranaceaTrichophorum caespitosumScirpoides burkeiIsolepis cernuaScleria distansCarex confertaOreobolus kuekenthaliiEleocharis atropurpureaCaustis dioicaBecquerelia cymosaColeochloa abyssinicaCladium jamaicenseLepironia articulataEriophorum vaginatumActinoscirpus grossusAmorphophallus rivieriAnomochloa marantoideaMapania cuspidataStenomesson pearceiLycoris sanguineaGalanthus plicatusLeucojum autumnaleDuckeella adolphiiHeteranthera dubiaAmaryllis belladonnaHemiphylacus latifoliaDressleria eburneaOrnithogalum longebracteatumEriocaulon microcephalusAllium altaicumTricoryne sp.Neofinetia falcataStellilabium pogonostalixOncidium excavatumGilliesia gramineaWashingtonia robustaParadisea liliastrumSolaria atropurpureaWhiteheadia bifoliaChlorogalum pomeridianumAnthericum liliagoLeucocoryne coquimbensisEriopsis bilobaPabellonia incrassataNothoscordum bivalvePatersonia glabrataSparattanthelium wonotoboenseGeorgeantha hexandraEcdeiocolea monostachyaCamassia leichtliniiArisaema triphyllumSmilacina hondoensisMaianthemum dilatatumAsphodelus aestivusSemele androgynaRuscus aculeatusDanae racemosaOxychloe andinaAlbuca shawiiPolygonatum cirrhifoliumCardiocrinum cordatumZantedeschia aethiopicaTofieldia pusillaAplectrum hyemaleXerophyllum tenaxOrontium aquaticumArundina graminifoliaLiparis lilifoliaMasdevallia infractaPeganum harmalaEarina autumnalisGinkgo bilobaStanhopea ecornutaBloomeria croceaPhyllanthus liebmannianusMaxillaria cucullataNeomoorea irrorataAngraecum sesquipedaleMuscari neglectumTapeinochilos ananassaePhilodendron oxycardiumHypolytrum bullatumOrchidantha fimbriataHypoxis glabellaPauridia longitubaMilla bifloraTriteleia bridgesiiMuilla maritimaNypa fruticansDaphnandra repandulaLaureliopsis philippianaKadsura japonicaAnomatheca laxaEriochilus cucullatusLapageria roseaLiriodendron chinenseEremothamnus marlothianusGagea luteaIxia latifoliaMonimia ovalifoliaLavatera acerifoliaLaurelia novaezelandiaeMalacocarpus crithmifoliusCephalanthera damasoniumParis tetraphyllaCyanea coriaceaCollospermum hastatumPhilesia buxifoliaPasithea coeruleaBulbophyllum lobbiiEria ferrugineaDaiswa fargesiiPalmorchis trilobulataDieffenbachia sp. Qiu 96007Anisoptera marginataCrispiloba dispermaPhyllonoma laticuspisSerissa foetidaPeperomia sp. Qiu 91047Combretocarpus rotundatusXerorchis amazonicaMalaxis spicataArgostemma hookeriTernstroemia stahliiPodochilus cultratusCoelogyne cristataCalanthe vestitaEpipactis helleborineArpophyllum giganteumPhreatia sp. Chase O203Illigera luzonensisDacrycarpus imbricatusThunia albaSobralia macranthaAnisophyllea corneriPleurothallis endotrachysCyrtopodium andersoniiGlomera sp. Chase O555Cymbidium ensifoliumDioscorea bulbiferaDiaphananthe rutilaCoryanthes verrucolineataNageia falcatusEncyclia sp. KMC1998Trichotosia feroxMonocostus uniflorusRohdea japonicaMaranta leuconeuraCryptocentrum peruvianumSpiranthes cernuaXylobium sp. KMC1998Phaius minorDisporum nantouenseAlstroemeria sp.Meiracyllium trinasutumCattleya dowianaCatasetum expansumDiceratostele gabonensisCorymborkis sp. Chase O542Monophyllorchis sp. Chase O435Sowerbaea junceaAnarthria polyphyllaHopkinsia adscendensLyginia barbataMayaca fluviatilisMyrsiphyllum asparagoidesIriartea deltoideaScilla bifloraGrammatophyllum speciosumAphyllanthes monspeliensisSansevieria cylindricaDracaena aubreyanaPetersianthus africanusAporusa frutescensGaertnera sp.Psilanthus manniiPodococcus barteriCorybas diemenicusHabenaria repensDiuris sulphureaCaladenia cf. caerulea Chase OGlossodia majorChloraea sp. Chase O551Platanthera ciliarisOrthoceras strictumPonthieva racemosaPlatythelys querceticolaMicrotis parvifloraChiloglottis trapeziformisLyperanthus nigricansThelymitra sp. Chase O489Cryptostylis subulataCalochilus robertsoniCranichis fertilisLasianthus pedunculatusMycetia malayanaClintonia borealisPterostylis nutansGoodyera pubescensCyrilla racemifloraDillenia indicaBrownea arizaAldina latifoliaMyrospermum sousanumOchroma pyramidaleAdansonia rubrostipaPhylloxylon perrieriMoringa oleiferaCastanospermum australeRoussea simplexPlumeria inodoraGeosiris sp.Epistephium cf. lucidum ChaseCouepia robustaEuphronia guianensisAcioa guianensisCalophyllum sp.Caryocar glabrumKinugasa japonicaGarrya ellipticaAptosimum sp. DePamphilis HWBGAlseis lugonisBacopa carolinianaAscarina sp. QiuM149Alnus incanaAlvaradoa amorphoidesBrachyloma daphnoidesMelichrus procumbensRhodothamnus chamaecistusRhododendron hippophaeoidesMonotoca scopariaLeucothoe racemosaSprengelia incarnataAndersonia sprengelioidesOligarrhena micranthaCraibiodendron yunnanenseAndromeda polifoliaLyonia ligustrinaPrionotes cerinthoidesVaccinium meridionaleSatyria warszewicziiDiplycosia acuminataCyathodes glaucaArcheria comberiBudawangia gnidioidesEpacris lanuginosaCosmelia rubraRupicola sprengelioidesWoollsia pungensSphenotoma dracophylloidesLeucopogon gibbosusTrochocarpa gunniiAstroloma humifusumLysinema ciliatumCorrea pulchellaTricyrtis affinisTetramerista sp.Danais xanthorrhoeaCarpinus carolinianaAphanopetalum resinosum 940979Corylopsis paucifloraBoehmeria niveaCrossostylis bifloraByrsonima crassifoliaPeltanthera floribundaSterigmapetalum guianense subsSymplocos costataMyrsine africanaBessera elegansAeranthes ramosaPhilydrum lanuginosumLycomormium squalidumAcineta chrysanthaLycaste cruentaKegeliella kupperiVerbena officinalisHeteropolygonatum pendulumEriospermum bayeriThymelaea hirsutaMyrica ceriferaSkimmia anquetiliaDovyalis rhamnoidesDesfontainia spinosaDrimys winteriCryptocarya obovataRothmannia longifloraCorokia cotoneasterIxerba brexioidesLonicera orientalisCurtisia dentataMorus albaMaclura pomiferaGoodia lotifoliaKandelia candelScyphiphora hydrophyllaceaDombeya sp. Chase 273Loeseneriella africanaErithalis fruticosaDriessenia glanduligeraAceratium ferrugineumSteganthera hirsutaMahonia bealeiHedera helixTeucridium parvifoliumShepherdia argenteaSaurauia nepaulensisClematoclethra lasiocladaActinidia chinensisTibouchina urvilleanaDiplectria divaricataSwartzia sp.Melissa officinalisOcimum basilicumHoffmannia refulgens X HoffmanAquilaria beccarianaMyrcianthes fragransChilocarpus suaveolensAmaracarpus sp. Parvis 680Declieuxia fruticosaDisporopsis arisanensisTrachelospermum jasminoidesCorynocarpus cribbianusLotus corniculatusHydnophytum formicarumMyrmecodia platyreaGravesia viscosaCubanola domingensisBuchanania latifoliaDeppea grandifloraMyroxylon balsamumCarallia brachiataArrabidaea pubescensOroxylum indicumHarpagophyton granidieriClavija eggersianaMeyna tetraphyllaKigelia africanaAntonia ovataChazaliella abruptaMacfadyena unguiscatiSukunia longipesCassipourea ceylanicaDactylopetalum ellipticifoliumRudgea lorentensisAlibertia edulisRandia aculeataCampsis radicansEuclinia longifloraPauridiantha paucinervisAmphitecna apiculataFaramea multifloraCrescentia portoricensisVangueria edulisEnterospermum coriaceumCanthium coromandelicumCollinsonia canadensisOrmosia emarginataTrichocladus crinitusLacunaria jenmaniiPachira aquaticaDryadodaphne sp. Gray 4853Touroulia guianensisElaeocarpus grandisLoropetalum chinenseBetula nigraNymphoides peltataDoryphora aromaticaAegiceras corniculatumPhellodendron amurensePassiflora quadrangularisPseudomonotes tropenbosiiPentace polyanthaTetraclea coulteriBrownlowia elataDiospyros kakiNelsonia campestrisMussaenda erythrophyllaIpomoea purpureaMimulus aurantiacusNeuburgia corynocarpumBaissea leonensisGeum chiloenseHolarrhena pubescensFuntumia elasticaSecamone afzeliiBeaumontia grandifloraMandevilla sanderiDictyophleba lucidaStrophanthus eminiiParsonsia heterophyllaParquetina nigrescensPrestonia quinquangularisPachypodium lamereiCeropegia woodiiBegonia boisianaHelmiopsiella madagascariensisEriolaena spectabilisCissampelos pareiraLantana camaraTuberaria guttataToisusu urbanianaChosenia arbutifoliaAdoxa moschatellinaCoprosma pumilaCladopus austroosumiensisOserya coulterianaMarathrum rubrumHydrobryum floribundumVanroyenella plumosaPodostemum ceratophyllumNertera granadensisSalix albaPremna microphyllaGuettarda uruguensisMarcgravia rectifloraReineckea carneaAsparagus officinalisBurchellia bubalinaTrochetiopsis erythroxylonRuizia cordataSeetzenia lanataQuiina pteridophyllaBurretiodendron esquiroliiHamelia cupreaChristiana africanaMatisia cordataParamelhania decaryanaAllocasuarina muellerianaDussia tessmanniiBrighamia insignisDelissea rhytidospermaRehderodendron macrocarpumHalesia carolinaSinojackia rehderianaSchinus molleToxicodendron radicansQuercus virginianaSargentodoxa cuneataElingamita johnsoniOsyris lanceolataOstryopsis davidianaSantalum albumLiquidambar styracifluaHoloptelea integrifoliaSideroxylon cinereumSchima superbaHeterocentron subtriplinerviumCorylus cornutaEubrachion ambiguumJeffersonia diphyllaSarcolaena oblongifoliaCarya glabraArgemone mexicanaGrevillea robustaFortunearia sinensisOstrya virginianaSanguinaria canadensisTrientalis europaeaGlaucidium palmatumHypseocharis sp.Listera smalliiBletilla striataConanthera campanulataHerpolirion novaezelandiaeAnemopsis californicaKunhardtia radiataOdontostomum hartwegiiHermannia erodioidesCypripedium irapeanumDais cotinifoliaGnetum parvifoliumLeonia glycycarpaPiptocalyx mooreiHennecartia omphalandraPetenaea cordataSpermadictyon suaveolensVirgilia divaricataRuta graveolensXymalos monosporaNicotiana debneyiChoisya mollisPhylica polifoliaWarszewiczia cordataArgophyllum sp.Trillium camtschatcensePalmeria scandensBurchardia umbellataErythronium japonicumLardizabala biternataJacquinia umbellataEmmenopterys henryiScabiosa sp. Albach 39Roupala macrophyllaPterostemon rotundifoliusIdesia polycarpaComptonia peregrinaCoopernookia strophiolataDiaspasis filifoliaKerria japonicaFagus crenataGoodenia ovataMyrothamnus flabellifoliusCaltha palustrisCondaminea corymbosaDrosera capensisPterocephalus lasiospermus 206Gaiadendron punctatumNesiota ellipticaSelliera radicansSaxifraga integrifoliaPlatytheca verticellataPeumus boldusItea virginicaPogonopus speciosusAlberta magnaRustia splendensRanzania japonicaSoldanella montanaLobelia cardinalisHeuchera micranthaPieris floribundaGaultheria miquelianaChimarrhis hookeriMelampyrum lineareOlea europaeaHedyosmum bonplandianumEuthystachys abbreviataStilbe vestitaLindenbergia philippinensisProboscidea louisianicaPhlox longifoliaStaphylea trifoliaAtuna racemosaColebrookea oppositifoliaPodranea ricasolianaTecoma stansRadermachera frondosaNectaroscordum siculumPrunella grandifloraOlinia ventosaCaulophyllum robustumMisodendron brachystachyumTrachelium caeruleumCalceolaria sp. dePamphilis 90Jovellana sp. DePamphilis 90 3Nothofagus alessandriiIva frutescensBaccharis halimifoliaHelianthus annuusBorrichia frutescensPentanopsis fragransConostomium quadrangulareKohautia caespitosaBouvardia glaberrimaSynaptantha tillaeaceaOldenlandia corymbosaPentodon pentandrusParapentas silvaticaCarphalea glaucescensPentanisia longitubaPlacopoda virgataHedyotis fruticosaSpermacoce tenuiorRichardia pilosaAmaranthus tricolorTheligonum cynocrambeHydrophyllum virginianumEriodictyon californicumBorago officinalis336406Eccremocarpus scaberLavandula angustifoliaSatureja hortensisHorminum pyrenaicumHyssopus officinalisDracocephalum grandiflorumLamium albumPedicularis foliosaHemimeris sabulosaNuxia sp. Hedberg 4731Peltoboykinia tellimoidesNotholirion thomsonianumMilligania densifloraCorydalis nobilisDarlingtonia californicaPlatanus occidentalisAntidaphne viscoideaDrosera regiaTiarella polyphyllaChrysosplenium albumDiervilla sessilifoliaLeptarrhena pyrolifoliaScoliopus bigeloviiTrochodendron aralioidesAsteropyrum cavalerieiLilium japonicumNomocharis pardanthinaAlania endlicheriFritillaria agrestisDecaisnea fargesiiNepeta tuberosaTeucrium chamaedrysTeline canariensisLaburnum anagyroidesArgyrocytisus battandieriChamaecytisus austriacusChamaespartium sagittaleAdenocarpus complicatusCalicotome villosaCytisus arboreusCytisophyllum sessilifoliumPetteria ramentaceaSpartocytisus supranubiusPolygala amaraSinapis albaRogiera suffrutescensHelianthemum grandiflorumOtholobium sericeumCistus revoliiErythrina cristagalliCajanus cajanBituminaria bituminosaNapoleonaea vogeliiGuarea glabraSpartium junceumLupinus albescensErinacea anthyllisLotononis galpinii I Eisen et al., 2002
    91. 91. TIGRTIGR PG Profile of C. tepidum RbcL suggests link with Sulfur Metabolism from Eisen et al., 2002 and see Hanson and Tabita 2001 CT1893 sulfhydrogenase, delta subunit hydDCT1681 ABC transporter, permease proteinCT2206 polysaccharide efflux transporter, putativeCT1271 glycosyl transferaseCT1965 conserved hypothetical proteinCT2256 geranylgeranyl hydrogenase bchPCT0011 deoxyhypusine synthase, putativeCT1772 ribulose bisphosphate carboxylase, large subunit rbcLCT1894 sulhydrogenase, alpha subunit hydACT0472 conserved hypothetical proteinCT0274 carbon-nitrogen hydrolase family proteinCT1891 sulfhydrogenase, beta subunit hydB-1CT1892 sulfhydrogenase, gamma subunit hydG-1CT1250 sulfhydrogenase, gamma subunit hydG-2CT1249 sulfhydrogenase, beta subunit hydB-2
    92. 92. TIGRTIGR PG Profiling Works Better Using Orthology Eisen and Wu 2002
    93. 93. TIGRTIGR Uses of Phylogenomics • Species evolution and systematics • Lateral versus vertical evolution • Gene function • Gene and genome duplications • Genome rearrangements
    94. 94. TIGRTIGR Uses of Phylogenomics • Species evolution and systematics • Lateral versus vertical evolution • Gene function • Gene and genome duplications • Genome rearrangements
    95. 95. TIGRTIGR Why Duplications Are Useful to Identify • Allows division into orthologs and paralogs • Improves functional predictions • Helps identify mechanisms of duplication • Can be used to study mutation processes in different parts of a genome • Lineage specific duplications may be indicative of species’ specific adaptations
    96. 96. TIGRTIGR Levels of Paralogy Within A Genome • All – All members of a gene family are linked together • Top matches – Only top matching pairs are linked together. Therefore, if in a large gene family, only the pair from the most recent duplication event is included • Recent – Operational definition based on comparison to other species. Only pairs which are more similar to each other than to selected other species are included.
    97. 97. TIGRTIGR C. pneumoniae Paralogs by Position 0 250000 500000 750000 1000000 1250000 Subject Orf Position 0 250000 500000 750000 1000000 1250000 Query Orf Position
    98. 98. TIGRTIGR C. pneumoniae Paralogs - Lineage Specific 0 250000 500000 750000 1000000 1250000 Subject Orf Position 0 250000 500000 750000 1000000 1250000 Query Orf Position
    99. 99. TIGRTIGR Expansion of MCP Family in V. choleraeE.coli gi1787690B.subtilis gi2633766Synechocystis sp. gi1001299Synechocystis sp. gi1001300Synechocystis sp. gi1652276Synechocystis sp. gi1652103H.pylori gi2313716H.pylori99 gi4155097C.jejuni Cj1190cC.jejuni Cj1110cA.fulgidus gi2649560A.fulgidus gi2649548B.subtilis gi2634254B.subtilis gi2632630B.subtilis gi2635607B.subtilis gi2635608B.subtilis gi2635609B.subtilis gi2635610B.subtilis gi2635882E.coli gi1788195E.coli gi2367378E.coli gi1788194E.coli gi1789453C.jejuni Cj0144C.jejuni Cj0262cH.pylori gi2313186H.pylori99 gi4154603C.jejuni Cj1564C.jejuni Cj1506cH.pylori gi2313163H.pylori99 gi4154575H.pylori gi2313179H.pylori99 gi4154599C.jejuni Cj0019cC.jejuni Cj0951cC.jejuni Cj0246cB.subtilis gi2633374T.maritima TM0014T.pallidum gi3322777T.pallidum gi3322939T.pallidum gi3322938B.burgdorferi gi2688522T.pallidum gi3322296B.burgdorferi gi2688521T.maritima TM0429T.maritima TM0918T.maritima TM0023T.maritima TM1428T.maritima TM1143T.maritima TM1146P.abyssi PAB1308P.horikoshii gi3256846P.abyssi PAB1336P.horikoshii gi3256896P.abyssi PAB2066P.horikoshii gi3258290P.abyssi PAB1026P.horikoshii gi3256884D.radiodurans DRA00354D.radiodurans DRA0353D.radiodurans DRA0352P.abyssi PAB1189P.horikoshii gi3258414B.burgdorferi gi2688621M.tuberculosis gi1666149V.cholerae VC0512V.cholerae VCA1034V.cholerae VCA0974V.cholerae VCA0068V.cholerae VC0825V.cholerae VC0282V.cholerae VCA0906V.cholerae VCA0979V.cholerae VCA1056V.cholerae VC1643V.cholerae VC2161V.cholerae VCA0923V.cholerae VC0514V.cholerae VC1868V.cholerae VCA0773V.cholerae VC1313V.cholerae VC1859V.cholerae VC1413V.cholerae VCA0268V.cholerae VCA0658V.cholerae VC1405V.cholerae VC1298V.cholerae VC1248V.cholerae VCA0864V.cholerae VCA0176V.cholerae VCA0220V.cholerae VC1289V.cholerae VCA1069V.cholerae VC2439V.cholerae VC1967V.cholerae VCA0031V.cholerae VC1898V.cholerae VCA0663V.cholerae VCA0988V.cholerae VC0216V.cholerae VC0449V.cholerae VCA0008V.cholerae VC1406V.cholerae VC1535V.cholerae VC0840V.cholerae VC0098V.cholerae VCA1092V.cholerae VC1403V.cholerae VCA1088V.cholerae VC1394V.cholerae VC0622NJ******************************************************************************* Heidelberg et al. (2000)
    100. 100. TIGRTIGR B. anthracis lineage specific duplications ORF04205 molybdopterin biosynthesis protein MoeA (moeA) ORF05907 molybdopterin biosynthesis protein MoeA (moeA) ORF02636 molybdopterin biosynthesis protein MoeA (moeA) ORF04204 molybdopterin biosynthesis protein MoeB, putative ORF05908 molybdopterin biosynthesis protein MoeB, putative ORF02634 molybdopterin biosynthesis protein MoeB, putative ORF05904 molybdopterin converting factor, subunit 1 (moaD) ORF02639 molybdopterin converting factor, subunit 1 (moaD) ORF04206 molybdopterin converting factor, subunit 2 (moaE) ORF05905 molybdopterin converting factor, subunit 2 (moaE) ORF02638 molybdopterin converting factor, subunit 2 (moaE) Based on Read et al. submitted
    101. 101. TIGRTIGR S. aureus Lineage Specific Duplications ORF02715 4-diphosphocytidyl-2C-methyl-D-erythritol synthase, putative ORF02712 alcohol dehydrogenase, zinc-containing ORF00701 alpha-hemolysin precursor (2X) ORF00717 antibacterial protein ORF02597 capsular polysaccharide biosynthesis proteins CapABC (2X) ORF00804 cell wall hydrolase (3X) ORF00657 cell wall surface anchor family protein (2X) ORF00358 clumping factor (2X) ORF01758 deoxyribose-phosphate aldolase (deoC) ORF02579 purine nucleoside phosphorylase (deoD) ORF01031 drug transporter, putative ORF00805 endopeptidase resistance gene (eprH) ORF00706 exotoxin 1,3,4,5, unknown (2X) ORF02184 fibronectin(2X) ORF00097 glycosyl transferase, group 1 family protein (3X) ORF02086 IgG-binding protein (2X) ORF02431 integrase/recombinase, core domain family (3X) Analysis done with S. Gill
    102. 102. TIGRTIGR S. aureus Lineage Specific Duplications ORF00137 conserved hypothetical protein ORF00138 conserved hypothetical protein ORF00139 conserved hypothetical protein ORF00140 conserved hypothetical protein ORF00141 conserved hypothetical protein ORF00142 conserved hypothetical protein ORF00143 conserved hypothetical protein ORF00144 conserved hypothetical protein ORF00145 conserved hypothetical protein ORF00146 conserved hypothetical protein ORF00148 conserved hypothetical protein ORF00667 conserved hypothetical protein ORF01251 conserved hypothetical protein ORF02160 conserved hypothetical protein ORF02166 conserved hypothetical protein ORF02170 conserved hypothetical protein ORF02171 conserved hypothetical protein ORF02507 conserved hypothetical protein ORF02745 conserved hypothetical protein ORF02760 conserved hypothetical protein ORF02762 conserved hypothetical protein ORF02763 conserved hypothetical protein ORF02766 conserved hypothetical protein ORF02768 conserved hypothetical protein ORF02769 conserved hypothetical protein ORF02770 conserved hypothetical protein ORF02771 conserved hypothetical protein ORF02772 conserved hypothetical protein ORF02773 conserved hypothetical protein ORF02774 conserved hypothetical protein ORF02896 conserved hypothetical protein ORF02974 conserved hypothetical protein ORF02711 conserved hypothetical protein UPF0007 ORF02614 conserved hypothetical protein, authentic frameshift ORF00286 hypothetical protein ORF00338 hypothetical protein ORF00361 hypothetical protein ORF00412 hypothetical protein ORF00415 hypothetical protein ORF00614 hypothetical protein ORF00697 hypothetical protein ORF00703 hypothetical protein ORF00705 hypothetical protein ORF00875 hypothetical protein ORF00876 hypothetical protein ORF00877 hypothetical protein ORF00879 hypothetical protein ORF00888 hypothetical protein ORF00889 hypothetical protein ORF01024 hypothetical protein ORF01041 hypothetical protein ORF01089 hypothetical protein ORF01091 hypothetical protein ORF01092 hypothetical protein ORF01093 hypothetical protein ORF01095 hypothetical protein ORF01446 hypothetical protein ORF01462 hypothetical protein ORF01918 hypothetical protein ORF02099 hypothetical protein ORF02102 hypothetical protein ORF02158 hypothetical protein ORF02159 hypothetical protein ORF02172 hypothetical protein ORF02430 hypothetical protein ORF02434 hypothetical protein ORF02530 hypothetical protein ORF02531 hypothetical protein ORF02532 hypothetical protein ORF02533 hypothetical protein ORF02534 hypothetical protein Analysis done with S. Gill
    103. 103. TIGRTIGR Lineage Specific Duplications in Wolbachia wMel Annotation ankyrin repeat domain protein ankyrin repeat domain protein ankyrin repeat domain protein ankyrin repeat domain protein ankyrin repeat domain protein ankyrin repeat domain protein ankyrin repeat domain protein conserved domain protein conserved domain protein conserved domain protein conserved domain protein conserved hypothetical protein conserved hypothetical protein conserved hypothetical protein conserved hypothetical protein conserved hypothetical protein conserved hypothetical protein conserved hypothetical protein conserved hypothetical protein conserved hypothetical protein conserved hypothetical protein conserved hypothetical protein conserved hypothetical protein conserved hypothetical protein conserved hypothetical protein conserved hypothetical protein conserved hypothetical protein conserved hypothetical protein conserved hypothetical protein conserved hypothetical protein conserved hypothetical protein conserved hypothetical protein conserved hypothetical protein conserved hypothetical protein conserved hypothetical protein FRAMESHIFT conserved hypothetical protein POINT MUTATION conserved hypothetical protein, degenerate conserved hypothetical protein, FRAMESHIFT conserved hypothetical protein, FRAMESHIFT conserved hypothetical protein, FRAMESHIFT conserved hypothetical protein, FRAMESHIFT conserved hypothetical protein, interruption-C conserved hypothetical protein, POINT MUTATION conserved hypothetical protein, POINT MUTATION conserved hypothetical protein, truncated conserved hypothetical protein, truncation DNA mismatch repair protein MutL (mutL) DNA repair protein RadC, putative DNA repair protein RadC, putative, truncation DNA repair protein RadC, truncation DnaJ domain protein DnaJ domain protein exopolysaccharide synthesis protein ExoD-related protein exopolysaccharide synthesis protein ExoD-related protein HNH endonuclease family protein HNH endonuclease family protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein hypothetical protein major facilitator family transporter major facilitator family transporter major facilitator family transporter membrane protein, putative membrane protein, putative membrane protein, putative MutL family protein Na+/H+ antiporter family protein Na+/H+ antiporter, putative permease, putative portal protein, FRAMESHIFT portal protein, FRAMESHIFT prophage LambdaW1, DNA methylase prophage LambdaW1, terminase large subunit, putative prophage LambdaW2, ankyrin repeat domain protein prophage LambdaW2, ankyrin repeat domain protein prophage LambdaW2, baseplate assembly protein J, putative prophage LambdaW2, baseplate assembly protein V, putative FRAMESHIFT prophage LambdaW2, baseplate assembly protein V, putative FRAMESHIFT prophage LambdaW2, baseplate assembly protein W, putative prophage LambdaW2, minor tail protein Z, putative, FRAMESHIFT prophage LambdaW2, site- specific recombinase, resolvase family prophage LambdaW4, ankyrin repeat domain protein prophage LambdaW4, DNA methylase prophage LambdaW4, portal protein, FRAMESHIFT prophage LambdaW4, portal protein, FRAMESHIFT prophage LambdaW4, terminase large subunit, putative prophage LambdaW5, ankyrin repeat domain protein prophage LambdaW5, ankyrin repeat domain protein prophage LambdaW5, ankyrin repeat domain protein prophage LambdaW5, baseplate assembly protein J, putative, FRAMESHIFT prophage LambdaW5, baseplate assembly protein V, putative prophage LambdaW5, baseplate assembly protein W, putative prophage LambdaW5, minor tail protein Z, putative, degenerate, FRAMESHIFT prophage LambdaW5, site- specific recombinase, resolvase family regulatory protein RepA, putative regulatory protein RepA, putative reverse transcriptase, putative reverse transcriptase, putative reverse transcriptase, putative sodium/alanine symporter family protein sodium/alanine symporter family protein TenA/THI-4 family protein transcriptional regulator transcriptional regulator transcriptional regulator transcriptional regulator transcriptional regulator transcriptional regulator transcriptional regulator, putative translation elongation factor Tu (tuf) translation elongation factor Tu (tuf) transposase, degenerate transposase, IS4 family transposase, IS4 family transposase, IS4 family transposase, IS5 family, interruption-N transposase, IS5 family, truncation transposase, putative, degenerate transposase, putative, degenerate transposase, putative, degenerate type IV secretion system protein VirB4, putative UDP-N-acetylglucosamine pyrophosphorylase-related protein
    104. 104. TIGRTIGR MutL Duplication in Wolbachia wMel ORF01096 DNA mismatch repair protein MutL (mutL) ORF00446 MutL family protein
    105. 105. TIGRTIGR MutL Duplication in Wolbachia wMel
    106. 106. TIGRTIGR Superoxide Dismutase Duplication in D. radiodurans D. radiodurans 2 D. radiodurans 1 V. cholerae E. coli M. tuburculosis B. subtilis A. aeolicus 1 A. aeolicus 2 C. elegans Yeast see White et al. (1999)
    107. 107. TIGRTIGR Archglbs fulgidus 2650206Archglbs profundus 3892197Desulfovibrio vulgaris 902747Dslfotomaculum thermocistern 1Chlorobium tepdum CT0852Chlorobium tepdum CT2249Allochromatium vinosum 2576393Pyrobaculum islandicum 2459568Archglbs fulgidus 2650205Archglbs profundus 389219Dslfotomaculum thermocistern 2Desulfovibrio vulgaris 902748Chlorobium tepdum CT0853Chlorobium tepdum CT2248Allochromatium vinosum 2576394Pyrobaculum islandicum 2459569Desulfovibrio vulgaris 1591554Methanobacterium thermoautotrophiucm coF420 2621331100901009510099100100989910010086100100 DsrBDsrCDuplication of DsrBC Recent Duplication of DsrBC in C. tepidum
    108. 108. TIGRTIGR 0.1 Schizosaccharomyces pombeGP139 Neurospora crassaPIRS55262S552 Clostridium perfringensGP18145 Bacillus subtilisSPP45864YWJD Bacillus cereusGP6759487embCAB B BACAN 01914 UV endonuclease Bacillus haloduransOMNINTL01BH B BACAN 01459 UV endonuclease Deinococcus radioduransGP61167 Nostoc sp. PCC 7120GP17130610d Older Duplication of UVDE
    109. 109. TIGRTIGR Uses of Phylogenomics • Species evolution and systematics • Lateral versus vertical evolution • Gene function • Gene and genome duplications • Genome rearrangements
    110. 110. TIGRTIGR X-files Eisen et al. 2000. Genome Biology 1(6): 11.1-11.9 Also see Tillier and Collins. 2000. Nature Genetics 26(2):195-7 and Suyama and Bork. 2001. Trends Genetics 17: 10-13.
    111. 111. TIGRTIGR V. cholerae vs. E. coli All 0 1000000 2000000 3000000 4000000 5000000 E. coli Coordinates 0 1000000 2000000 3000000 V. cholerae Coordinates
    112. 112. TIGRTIGR V. cholerae vs. E. coli Best 0 1000000 2000000 3000000 4000000 5000000 E. coli Coordinates 0 1000000 2000000 3000000 V. cholerae Coordinates
    113. 113. TIGRTIGR V. cholerae vs. E. coli if Top 0 1000000 2000000 3000000 4000000 5000000 E. coli Coordinates 0 1000000 2000000 3000000 V. cholerae Coordinates
    114. 114. TIGRTIGR V. cholerae vs. E. coli Top Matches, Rotated 0 1000000 2000000 3000000 4000000 5000000 E. coli ORF Coordinates 0 500000 1000000 1500000 2000000 2500000 3000000 V. cholerae ORF Coordinates
    115. 115. TIGRTIGR Duplication and Gene Loss Model 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’
    116. 116. TIGRTIGR B1A1B2A2B3A3B3B22423222120191817161514131211109672582627282930123453132 B131326789101112131415161718192021222324252627282930123453132 B32423222120191817161514131211109672582627282933231304521 A131326789101112131415161718192021222324252627282930123453132 A231326789101112131918171615142021222324252627282930123453132 A32678910111213191817161514202122232425262754331302928132 B2Inversion Around Terminus (*) Inversion Around Terminus (*) Inversion Around Origin (*) Inversion Around Origin (*) ******** Common Ancestor of A and B 31326789101112131415161718192021222324252627282930123453132 A2A1A2A3B2B1 Symmetric Inversion Model
    117. 117. TIGRTIGR V. cholerae vs. E. coli Best Matching Proteins by Location 0 1000000 2000000 3000000 4000000 5000000 E. coli ORF Coordinates 0 500000 1000000 1500000 2000000 2500000 3000000 V. cholerae ORF Coordinates
    118. 118. TIGRTIGR C. trachomatis MoPn C.pneumoniaeAR39 Origin Terminus C. trachomatis vs C. pneumoniae Dot Plot
    119. 119. TIGRTIGR M. leprae vs. M. tuberculosis Whole Genome Alignment 0 1000000 2000000 3000000 4000000 Mycobacterium tuberculosis 0 1000000 2000000 3000000 Mycobacterium leprae
    120. 120. TIGRTIGR B. subtilis vs. S. auerus 0 500 1000 1500 2000 2500 3000 2632200 2632700 2633200 2633700 2634200 2634700 2635200 2635700 2636200 2636700 analysis w/ S. Gill
    121. 121. TIGRTIGR P. putida vs. P.aeruginosa Orthologs 9945700 9946700 9947700 9948700 9949700 9950700 9951700 0 2000 4000 6000 8000 Series1 analysis w/ K. Nelson
    122. 122. TIGRTIGR StrpB vs. StrpA All 13621300 13621500 13621700 13621900 13622100 13622300 13622500 13622700 13622900 13623100 0 500 1000 1500 2000 2500 Series1
    123. 123. TIGRTIGR StrpB vs. StrpA: Orthologs 13621300 13621500 13621700 13621900 13622100 13622300 13622500 13622700 13622900 13623100 0 500 1000 1500 2000 2500 Series1
    124. 124. TIGRTIGR Why are Inversions Symmetrical Around Origin • Genetic studies in Salmonella and E. coli suggest that there may be strong selection against other inversions • See: – Mahan, Segall, Schmid and Roth – Liu and Sanderson – Rebollo, Francois, and, Louarn
    125. 125. TIGRTIGR Acknowledgements • Outside TIGR –A. Stoltzfus –H. Ochman –D. Bryant –W. F. Doolittle –M. Eisen –M-I Benito • $$$: –NSF –NIH –ONR –DOE –NEB