Phylogenomics and the Diversity           and Diversification of Microbes                            Jonathan A. Eisen     ...
My Obsessions                            Jonathan A. Eisen                               UC Davis                         ...
Monday, February 14, 2011
Social Networking in ScienceHOME PAGE         MY TIMES       TODAYS PAPER   VIDEO   MOST POPULAR   TIMES TOPICS           ...
Bacterial evolveMonday, February 14, 2011
Phylogenomics of NoveltyMonday, February 14, 2011
Phylogenomics of Novelty                            Mechanisms of                            Origin of New                ...
Phylogenomics of Novelty                            Mechanisms of     Variation in                            Origin of Ne...
Phylogenomics of Novelty                            Mechanisms of         Variation in                            Origin o...
Phylogenomics of Novelty                                  • How does novelty originate?                                  •...
Phylogenomics of Novelty                                            • How does novelty originate?                         ...
Phylogenomics of Novelty   • Patterns of variation      • Within species      • Between species   • Causes      • Variatio...
Phylogenomics of Novelty   • Patterns of variation      • Within species                  Variation in      • Between spec...
Phylogenomics of Novelty                   • Information needed to distinguish convergence from                   homology...
Phylogenomics of Novelty                   • Information needed to distinguish convergence from                   homology...
Phylogenomics of Novelty                                                   Variation in      Mechanisms of                ...
Phylogenomics of Novelty                                                   Variation in      Mechanisms of                ...
Why do this?         • Discover causes and effects of differences in           evolvability         • Improve predictions ...
Outline         • Introduction         • Phylogenomic Stories               –   Within genome invention of novelty        ...
Introduction                            Genome SequencingMonday, February 14, 2011
rRNA Tree of Life                             FIgure from Barton, Eisen et al.                                “Evolution”,...
Limited Sampling of RRR Studies                             FIgure from Barton, Eisen et al.                              ...
Limited Sampling of RRR Studies                                                                Haloferax                  ...
UV Survival E.coli vs H.volcanii                1                            Ecoli vs. Hvolcanii              0.1         ...
H. volcanii UV Repair Label 7 - 45J / m2)     0.6                                               Label5#2                  ...
Fleischmann et al.                            1995Monday, February 14, 2011
Limited Sampling of RRR Studies                                                                Haloferax                  ...
From http://genomesonline.orgMonday, February 14, 2011
Monday, February 14, 2011
Monday, February 14, 2011
Monday, February 14, 2011
Human commensalsMonday, February 14, 2011
From http://genomesonline.orgMonday, February 14, 2011
Phylogenomics of Novelty I                        Origin of Functions from WithinMonday, February 14, 2011
Phylogenomics of Novelty                                  • How does novelty originate?                                  •...
Phylogenomics of Novelty                                            • How does novelty originate?                         ...
From Eisen et al.                            1997 Nature                            Medicine 3:                           ...
Blast Search of H. pylori “MutS”         • Blast search pulls up Syn. sp MutS#2 with much higher p           value than ot...
Predicting Function         • Identification of motifs               – Short regions of sequence similarity that are indic...
MutL??                            Based on Eisen et al. 1997 Nature Medicine 3: 1076-1078.Monday, February 14, 2011
Overlaying Functions onto Tree                                                                              MutS2         ...
Monday, February 14, 2011
Evolutionary Functional Prediction                                         EXAMPLE A                                METHOD...
Example 2: Recent Changes        • Phylogenomic functional prediction         NJ                                          ...
Tetrahymena Genome Processing                               • Probably exists as a defense mechanism                      ...
Conclusions         • Enormous variation in processes underlying           origin of novelty         • See within genomes ...
Phylogenomics of Novelty II              Sometimes, it is easier to steal, borrow, or               coopt functions rather...
Stealing DNAMonday, February 14, 2011
rRNA Tree of Life                            Bacteria                                                                   Ar...
Perna et al. 2003Monday, February 14, 2011
Network of Life                            Bacteria                                                                   Arch...
A. thaliana T1E2.8 is a                            Chloroplast Derived HSP60Monday, February 14, 2011
Phylogenetic Distribution Novelty:                   Bacterial Actin Related Protein                                      ...
Correlated gain/loss of genes         • Microbial genes are lost rapidly when not           maintained by selection       ...
Non-Homology Predictions:               Phylogenetic Profiling          • Step 1: Search all genes in            organisms...
Carboxydothermus hydrogenoformans   • Isolated from a Russian hotspring   • Thermophile (grows at 80°C)   • Anaerobic   • ...
Homologs of Sporulation Genes                                          Wu et al. 2005                                     ...
Carboxydothermus sporulates                            Wu et al. 2005 PLoS Genetics 1: e65.Monday, February 14, 2011
Wu et al. 2005 PLoS Genetics 1: e65.Monday, February 14, 2011
Stealing Organisms (Symbioses)Monday, February 14, 2011
Mutualistic Genome Evolution         • Compare and contrast different types of           mutualistic symbioses         • D...
Glassy Winged Sharpshooter                                     • Feeds on xylem                                       sap ...
Sharpshooter Shotgun Sequencing                                                  shotgun                       Collaborati...
Monday, February 14, 2011
Monday, February 14, 2011
Monday, February 14, 2011
Higher Evolutionary Rates in                         Endosymbionts   Wu et al. 2006 PLoS Biology 4: e188. Collaboration wi...
Variation in Evolution Rates                                                                   MutS         MutL          ...
Polymorphisms in Metapopulation     • Data from ~200 hosts           – 104 SNPs           – 2 indels     • PCR surveys sho...
Baumannia is a Vitamin and                    Cofactor Producing Machine                                                 W...
No Amino-Acid SynthesisMonday, February 14, 2011
Monday, February 14, 2011
The Uncultured MajorityMonday, February 14, 2011
Great Plate Count Anomaly                        Culturing   Microscope                            Count    CountMonday, F...
Great Plate Count Anomaly                        Culturing       Microscope                            Count   <<<< CountM...
Great Plate Count Anomaly                                                     DNA                        Culturing       M...
rRNA PCR     The Hidden Majority                      Richness estimates                            Hugenholtz 2002       ...
Monday, February 14, 2011
rRNA data increasing exponentially tooMonday, February 14, 2011
Perna et al. 2003Monday, February 14, 2011
Metagenomics                                     shotgun                                               cloneMonday, Februa...
Monday, February 14, 2011
How can we best use                            metagenomic data?         • Many possible uses including:               – I...
Example I: Phylotyping with                   rRNA and other genesMonday, February 14, 2011
Functional Diversity of Proteorhodopsins?                                         Venter et al., 2004Monday, February 14, ...
Weighted % of Clones                                                                                                      ...
Example II: BinningMonday, February 14, 2011
Metagenomics ChallengeMonday, February 14, 2011
Binning challenge      A                                         T      B                                         U      C...
Binning challenge      A                                                          T      B                                ...
Binning challenge      A                                                          T      B                                ...
Binning challenge      A                                                        T      B                                  ...
Binning challenge      A                                                        T      B                                  ...
Monday, February 14, 2011
No Amino-Acid SynthesisMonday, February 14, 2011
Monday, February 14, 2011
???????Monday, February 14, 2011
CFB PhylaMonday, February 14, 2011
Sulcia makes amino acids   Baumannia makes vitamins and cofactors                            Wu et al. 2006 PLoS Biology 4...
Phylogenomics of Novelty III                        Knowing What We Don’t KnowMonday, February 14, 2011
Research Topics                                                    Variation in      Mechanisms of                        ...
Research Topics                                                    Variation in      Mechanisms of                        ...
As of 2002Monday, February 14, 2011
As of 2002                  Proteobacteria                            TM6                            OS-K                 ...
As of 2002                  Proteobacteria                            TM6                            OS-K                 ...
As of 2002                  Proteobacteria                            TM6                            OS-K                 ...
As of 2002                  Proteobacteria                            TM6                            OS-K                 ...
Proteobacteria• NSF-funded                TM6                            OS-K                                             ...
Monday, February 14, 2011
Proteobacteria• NSF-funded                TM6                            OS-K                                             ...
Proteobacteria• NSF-funded                TM6                            OS-K                                             ...
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
Phylogenomics Talk at UC Berkeley by J. A. Eisen
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Phylogenomics Talk at UC Berkeley by J. A. Eisen

  1. 1. Phylogenomics and the Diversity and Diversification of Microbes Jonathan A. Eisen UC Davis UC Berkeley Talk February 3, 2011Monday, February 14, 2011
  2. 2. My Obsessions Jonathan A. Eisen UC Davis UC Berkeley Talk February 3, 2011Monday, February 14, 2011
  3. 3. Monday, February 14, 2011
  4. 4. Social Networking in ScienceHOME PAGE MY TIMES TODAYS PAPER VIDEO MOST POPULAR TIMES TOPICS Welcome, fcollins Member Center Log OutSunday, April 1, 2007 HealthWORLD U.S. N.Y. / REGION BUSINESS TECHNOLOGY SCIENCE HEALTH SPORTS OPINION ARTS STYLE TRAVEL JOBS REAL ESTATE AUTOS FITNESS & NUTRITION HEALTH CARE POLICY MENTAL HEALTH & BEHAVIORScientist Reveals Secret of the Ocean: Its HimBy NICHOLAS WADEPublished: April 1, 2007 PRINT nytimes.com/sportsMaverick scientist J. Craig Venter has done it again. It was just a few years SINGLE-PAGEago that Dr. Venter announced that the human genome sequenced by Celera SAVEGenomics was in fact, mostly his own. And now, Venter has revealed a second SHAREtwist in his genomic self-examination. Venter was discussing his Global SHAREOcean Voyage, in which he used his personal yacht to collect ocean watersamples from around the world. He then used large filtration units to collect How good is your bracket? Compare your tournament picks to choices from members of The New York Times sportsmicrobes from the water samples which were then brought back to his high desk and other players.tech lab in Rockville, MD where he used the same methods that were used to Also in Sports: The Bracket Blog - all the news leading up to the Finalsequence the human genome to study the genomes of the 1000s of ocean Fourdwelling microbes found in each sample. In discussing the sampling methods, Venter let slip his Bats Blog: Spring training updates Play Magazine: How to build a super athletelatest attack on the standards of science – some of the samples were in fact not from the ocean, butwere from microbial habitats in and on his body.“The human microbiome is the next frontier,” Dr. Venter said. “The ocean voyage was just a cover.My main goal has always been to work on the microbes that live in and on people. And now that mygenome is nearly complete, why not use myself as the model for human microbiome studies as well.”It is certainly true that in the last few years, the microbes that live in and on people have become ahot research topic. So hot that the same people who were involved in the race to sequence the humangenome have been involved in this race too. Francis Collins, Venter main competitor and still the Monday, February 14, 2011director of the National Human Genome Research Institute (NHGRI), recently testified before
  5. 5. Bacterial evolveMonday, February 14, 2011
  6. 6. Phylogenomics of NoveltyMonday, February 14, 2011
  7. 7. Phylogenomics of Novelty Mechanisms of Origin of New FunctionsMonday, February 14, 2011
  8. 8. Phylogenomics of Novelty Mechanisms of Variation in Origin of New Mechanisms: Functions Patterns, Causes and EffectsMonday, February 14, 2011
  9. 9. Phylogenomics of Novelty Mechanisms of Variation in Origin of New Mechanisms: Functions Patterns, Causes and Effects Species EvolutionMonday, February 14, 2011
  10. 10. Phylogenomics of Novelty • How does novelty originate? • Major categories of processes • From within • De novo invention • Simple substitutions • Duplication and divergence • Domain shuffling • Small & large rearrangements • Regulatory changes • From outside • Lateral gene transfer • SymbiosesMonday, February 14, 2011
  11. 11. Phylogenomics of Novelty • How does novelty originate? • Major categories of processes Mechanisms of • From within Origin of New • De novo invention Functions • Simple substitutions • Duplication and divergence • Domain shuffling • Small & large rearrangements • Regulatory changes • From outside • Lateral gene transfer • SymbiosesMonday, February 14, 2011
  12. 12. Phylogenomics of Novelty • Patterns of variation • Within species • Between species • Causes • Variation in replication, recombination and repair • Effects • Differences in evolvability • Ecological niche • Short and long term genome evolutionMonday, February 14, 2011
  13. 13. Phylogenomics of Novelty • Patterns of variation • Within species Variation in • Between species Mechanisms: • Causes Patterns, Causes • Variation in replication, and Effects recombination and repair • Effects • Differences in evolvability • Ecological niche • Short and long term genome evolutionMonday, February 14, 2011
  14. 14. Phylogenomics of Novelty • Information needed to distinguish convergence from homology • Allows inference of rates and patterns of change • Allows one to determine if something is a “one time” event or a common theme in many lineagesMonday, February 14, 2011
  15. 15. Phylogenomics of Novelty • Information needed to distinguish convergence from homology • Allows inference of rates and patterns of change • Allows one to determine if something is a “one time” event or a common theme in many lineages Species EvolutionMonday, February 14, 2011
  16. 16. Phylogenomics of Novelty Variation in Mechanisms of Mechanisms: Origin of New Patterns, Causes Functions and Effects Species EvolutionMonday, February 14, 2011
  17. 17. Phylogenomics of Novelty Variation in Mechanisms of Mechanisms: Origin of New Patterns, Causes Functions and Effects Focus Today on Using Sequence Information for All of This Species EvolutionMonday, February 14, 2011
  18. 18. Why do this? • Discover causes and effects of differences in evolvability • Improve predictions from genome analysis • Guide interpretation of biological dataMonday, February 14, 2011
  19. 19. Outline • Introduction • Phylogenomic Stories – Within genome invention of novelty – Stealing novelty – Communities of microbes – Community service and knowing what we don’t knowMonday, February 14, 2011
  20. 20. Introduction Genome SequencingMonday, February 14, 2011
  21. 21. rRNA Tree of Life FIgure from Barton, Eisen et al. “Evolution”, CSHL Press. Based on tree from Pace NR, 2003.Monday, February 14, 2011
  22. 22. Limited Sampling of RRR Studies FIgure from Barton, Eisen et al. “Evolution”, CSHL Press. Based on tree from Pace NR, 2003.Monday, February 14, 2011
  23. 23. Limited Sampling of RRR Studies Haloferax Methanococcus Chlorobium Deinococcus Thermotoga FIgure from Barton, Eisen et al. “Evolution”, CSHL Press. Based on tree from Pace NR, 2003.Monday, February 14, 2011
  24. 24. UV Survival E.coli vs H.volcanii 1 Ecoli vs. Hvolcanii 0.1 0.01Relative 0.001Survival 0.0001 1E-05 1E-06 1E-07 0 50 100 150 200 250 300 350 400 UV J/m2 E.coli NR10121 mfd- E.coli NR10125 mfd+ TIGR H.volcanii WFD11Monday, February 14, 2011
  25. 25. H. volcanii UV Repair Label 7 - 45J / m2) 0.6 Label5#2 0 J/m2 t0 45 J/m2 t0 45 J/m2 Photoreac. 45 J/m2 Dark 24 Hours 0.4 0.2 0 0 2000 4000 6000 8000 10000 12000 14000 16000 18000 Avg. Mol. Wt.(Base Pairs)Monday, February 14, 2011
  26. 26. Fleischmann et al. 1995Monday, February 14, 2011
  27. 27. Limited Sampling of RRR Studies Haloferax Methanococcus Chlorobium Deinococcus Thermotoga FIgure from Barton, Eisen et al. “Evolution”, CSHL Press. Based on tree from Pace NR, 2003.Monday, February 14, 2011
  28. 28. From http://genomesonline.orgMonday, February 14, 2011
  29. 29. Monday, February 14, 2011
  30. 30. Monday, February 14, 2011
  31. 31. Monday, February 14, 2011
  32. 32. Human commensalsMonday, February 14, 2011
  33. 33. From http://genomesonline.orgMonday, February 14, 2011
  34. 34. Phylogenomics of Novelty I Origin of Functions from WithinMonday, February 14, 2011
  35. 35. Phylogenomics of Novelty • How does novelty originate? • Major categories of processes • From within • De novo invention • Simple substitutions • Duplication and divergence • Domain shuffling • Small & large rearrangements • Regulatory changes • From outside • Lateral gene transfer • SymbiosesMonday, February 14, 2011
  36. 36. Phylogenomics of Novelty • How does novelty originate? • Major categories of processes Mechanisms of • From within Origin of New • De novo invention Functions • Simple substitutions • Duplication and divergence • Domain shuffling • Small & large rearrangements • Regulatory changes • From outside • Lateral gene transfer • SymbiosesMonday, February 14, 2011
  37. 37. From Eisen et al. 1997 Nature Medicine 3: 1076-1078.Monday, February 14, 2011
  38. 38. Blast Search of H. pylori “MutS” • Blast search pulls up Syn. sp MutS#2 with much higher p value than other MutS homologs • Based on this TIGR predicted this species had mismatch repair • Assumes functional constancy Based on Eisen et al. 1997 Nature Medicine 3: 1076-1078.Monday, February 14, 2011
  39. 39. 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 functionMonday, February 14, 2011
  40. 40. MutL?? Based on Eisen et al. 1997 Nature Medicine 3: 1076-1078.Monday, February 14, 2011
  41. 41. Overlaying Functions onto Tree MutS2 Aquae MSH5 Strpy Bacsu Synsp Deira Helpy Yeast Human Borbu Metth Celeg MSH6 mSaco Yeast Human Mouse Arath Yeast MSH4 Celeg Human Arath Human MSH3 Mouse Fly Spombe Yeast Xenla Rat Mouse Yeast Human MSH1 Spombe Yeast MSH2 Neucr Arath Aquae Trepa Chltr DeiraTheaq BacsuBorbu Thema SynspStrpy Based on Eisen, Ecoli Neigo 1998 Nucl Acids MutS1 Res 26: 4291-4300.Monday, February 14, 2011
  42. 42. Monday, February 14, 2011
  43. 43. Evolutionary Functional Prediction EXAMPLE A METHOD EXAMPLE B 2A CHOOSE GENE(S) OF INTEREST 5 3A 1 3 4 2B 2 IDENTIFY HOMOLOGS 5 1A 2A 1B 3B 6 ALIGN SEQUENCES 1A 2A 3A 1B 2B 3B 1 2 3 4 5 6 CALCULATE GENE TREE Duplication? 1A 2A 3A 1B 2B 3B 1 2 3 4 5 6 OVERLAY KNOWN FUNCTIONS ONTO TREE Duplication? 1 2 3 4 5 6 1A 2A 3A 1B 2B 3B INFER LIKELY FUNCTION OF GENE(S) OF INTEREST Ambiguous Duplication? Species 1 Species 2 Species 3 1A 1B 2A 2B 3A 3B 1 2 3 4 5 6 ACTUAL EVOLUTION (ASSUMED TO BE UNKNOWN) Based on Eisen, 1998 Genome Duplication Res 8: 163-167.Monday, February 14, 2011
  44. 44. Example 2: Recent Changes • Phylogenomic functional prediction NJ * ** V.cholerae0512 VC V.cholerae VCA1034 V.cholerae VC V.cholerae VC V.cholerae VC A0974 A0068 V.cholerae VC 0825 0282 may not work well for very newly V.cholerae VCA0906 V.cholerae VC A0979 V.cholerae VCA1056 V.cholerae VC1643 V.cholerae VC2161 ** V.cholerae VCA0923 ** V.cholerae VC0514 V.cholerae VC 1868 V.cholerae VC A0773 V.cholerae VC1313 evolved functions V.cholerae VC 1859 V.cholerae VC1413 V.cholerae VCA0268 ** V.cholerae VC A0658 V.cholerae VC 1405 * V.cholerae VC1298 V.cholerae VC1248 V.cholerae VCA0864 V.cholerae VCA0176 ** V.cholerae VCA0220 V.cholerae VC 1289 ** V.cholerae VC1069 A V.cholerae VC2439 • Can use understanding of origin of V.cholerae VC967 1 V.cholerae VC A0031 V.cholerae VC1898 V.cholerae VC A0663 V.cholerae VC0988 A V.cholerae VC0216 * V.cholerae VC0449 V.cholerae VCA0008 V.cholerae VC1406 V.cholerae VC 1535 novelty to better interpret these cases? V.cholerae VC0840 B.subtilis gi2633766 Synechocystis sp. gi1001299 * Synechocystis sp.gi1001300 * Synechocystis sp. gi1652276 * Synechocystis sp. gi1652103 H.pylori gi2313716 ** **H.pylori 99 gi4155097 C.jejuni Cj1190c C.jejuni Cj1110c A.fulgidus gi2649560 A.fulgidus gi2649548 ** B.subtilis gi2634254 • Screen genomes for genes that have B.subtilis gi2632630 B.subtilis gi2635607 B.subtilis gi2635608 ** B.subtilis gi2635609 ** ** B.subtilisgi2635882 gi2635610 B.subtilis E.coligi1788195 E.coli gi2367378 * ** E.coligi1788194 E.coli A1092 gi1787690 V.cholerae VC changed recently V.cholerae VC 0098 E.coli gi1789453 H.pylori gi2313186 H.pylori 99 gi4154603 ** C.jejuni Cj0144 C.jejuni Cj1564 **C.jejuni C.jejuni Cj0262c Cj1506c ** H.pylori gi2313163 * ** H.pylori 99 gi4154575 ** H.pylori gi2313179 H.pylori 99 gi4154599 – Pseudogenes and gene loss ** C.jejuni Cj0019c C.jejuni Cj0951c C.jejuni Cj0246c B.subtilis gi2633374 T.maritima TM0014 V.cholerae VC1403 V.cholerae VCA1088 T.pallidum gi3322777 ** T.pallidum gi3322939 ** T.pallidum gi3322938 B.burgdorferi gi2688522 – Contingency Loci T.pallidum gi3322296 B.burgdorferi gi2688521 * T.maritima TM0429 **T.maritima TM0918 * **T.maritima T.maritima TM0023 TM1428 T.maritima TM1143 T.maritima TM1146 P.abyssi PAB1308 P.horikoshii gi3256846 ** P.abyssiPAB1336 – Acquisition (e.g., LGT) ** P.horikoshii gi3256896 ** **P.abyssi PAB2066 ** P.horikoshii ** P.abyssi gi3258290 * PAB1026 ** P.horikoshii DRA00354 gi3256884 D.radiodurans D.radiodurans ** D.radioduransDRA0353 ** DRA0352 ** V.cholerae VC 1394 P.abyssi PAB1189 P.horikoshii gi3258414 – Unusual dS/dN ratios ** B.burgdorferi gi2688621 M.tuberculosis gi1666149 V.cholerae VC 0622 – Rapid evolutionary rates – Recent duplicationsMonday, February 14, 2011
  45. 45. Tetrahymena Genome Processing • Probably exists as a defense mechanism • Analogous to RIPPING and heterochromatin silencing • Presence of repetitive DNA in MAC but not TEs suggests the mechanism involves targeting foreign DNA • Thus unlike RIPPING ciliate processing does not limit diversification by duplication Eisen et al. 2006. PLoS Biology.Monday, February 14, 2011
  46. 46. Conclusions • Enormous variation in processes underlying origin of novelty • See within genomes -> between species • Knowledge about mechanisms and variation helps predictions of function and biology from analysis of sequence dataMonday, February 14, 2011
  47. 47. Phylogenomics of Novelty II Sometimes, it is easier to steal, borrow, or coopt functions rather than evolve them anewMonday, February 14, 2011
  48. 48. Stealing DNAMonday, February 14, 2011
  49. 49. rRNA Tree of Life Bacteria Archaea Eukaryotes FIgure from Barton, Eisen et al. “Evolution”, CSHL Press. Based on tree from Pace NR, 2003.Monday, February 14, 2011
  50. 50. Perna et al. 2003Monday, February 14, 2011
  51. 51. Network of Life Bacteria Archaea Eukaryotes Figure from Barton, Eisen et al. “Evolution”, CSHL Press. Based on tree from Pace NR, 2003.Monday, February 14, 2011
  52. 52. A. thaliana T1E2.8 is a Chloroplast Derived HSP60Monday, February 14, 2011
  53. 53. Phylogenetic Distribution Novelty: Bacterial Actin Related Protein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aliangium ochraceum DSM 14365 Patrik D’haeseleer, Adam Zemla, Victor KuninWu et al. 2009 Nature 462, 1056-1060 See also Guljamow et al. 2007 Current Biology.Monday, February 14, 2011
  54. 54. Correlated gain/loss of genes • Microbial genes are lost rapidly when not maintained by selection • Genes can be acquired by lateral transfer • Frequently gain and loss occurs for entire pathways/processes • Thus might be able to use correlated presence/absence information to identify genes with similar functionsMonday, February 14, 2011
  55. 55. Non-Homology Predictions: Phylogenetic Profiling • Step 1: Search all genes in organisms of interest against all other genomes • Ask: Yes or No, is each gene found in each other species • Cluster genes by distribution patterns (profiles)Monday, February 14, 2011
  56. 56. Carboxydothermus hydrogenoformans • Isolated from a Russian hotspring • Thermophile (grows at 80°C) • Anaerobic • Grows very efficiently on CO (Carbon Monoxide) • Produces hydrogen gas • Low GC Gram positive (Firmicute) • Genome Determined (Wu et al. 2005 PLoS Genetics 1: e65. )Monday, February 14, 2011
  57. 57. Homologs of Sporulation Genes Wu et al. 2005 PLoS Genetics 1: e65.Monday, February 14, 2011
  58. 58. Carboxydothermus sporulates Wu et al. 2005 PLoS Genetics 1: e65.Monday, February 14, 2011
  59. 59. Wu et al. 2005 PLoS Genetics 1: e65.Monday, February 14, 2011
  60. 60. Stealing Organisms (Symbioses)Monday, February 14, 2011
  61. 61. Mutualistic Genome Evolution • Compare and contrast different types of mutualistic symbioses • Diverse hosts, symbionts, biology, ages • Organelles, chemosymbioses, photosynthetic symbioses, nutritional symbioses • What are the rules & patterns?Monday, February 14, 2011
  62. 62. Glassy Winged Sharpshooter • Feeds on xylem sap • Vector for Pierce’s Disease • Potential bioterror agentMonday, February 14, 2011
  63. 63. Sharpshooter Shotgun Sequencing shotgun Collaboration with Nancy Wu et al. 2006 PLoS Biology 4: e188. Moran’s labMonday, February 14, 2011
  64. 64. Monday, February 14, 2011
  65. 65. Monday, February 14, 2011
  66. 66. Monday, February 14, 2011
  67. 67. Higher Evolutionary Rates in Endosymbionts Wu et al. 2006 PLoS Biology 4: e188. Collaboration with Nancy Moran’ s LabMonday, February 14, 2011
  68. 68. Variation in Evolution Rates MutS MutL + + + + + + + + _ _ _ _ Wu et al. 2006 PLoS Biology 4: e188. Collaboration with Nancy Moran’ s LabMonday, February 14, 2011
  69. 69. Polymorphisms in Metapopulation • Data from ~200 hosts – 104 SNPs – 2 indels • PCR surveys show that this is between host variation • Much lower ratio of transitions:transversions than in Blochmannia • Consistent with absence of MMR from BlochmanniaMonday, February 14, 2011
  70. 70. Baumannia is a Vitamin and Cofactor Producing Machine Wu et al. 2006 PLoS Biology 4: e188.Monday, February 14, 2011
  71. 71. No Amino-Acid SynthesisMonday, February 14, 2011
  72. 72. Monday, February 14, 2011
  73. 73. The Uncultured MajorityMonday, February 14, 2011
  74. 74. Great Plate Count Anomaly Culturing Microscope Count CountMonday, February 14, 2011
  75. 75. Great Plate Count Anomaly Culturing Microscope Count <<<< CountMonday, February 14, 2011
  76. 76. Great Plate Count Anomaly DNA Culturing Microscope Count <<<< CountMonday, February 14, 2011
  77. 77. rRNA PCR The Hidden Majority Richness estimates Hugenholtz 2002 Bohannan and Hughes 2003Monday, February 14, 2011
  78. 78. Monday, February 14, 2011
  79. 79. rRNA data increasing exponentially tooMonday, February 14, 2011
  80. 80. Perna et al. 2003Monday, February 14, 2011
  81. 81. Metagenomics shotgun cloneMonday, February 14, 2011
  82. 82. Monday, February 14, 2011
  83. 83. How can we best use metagenomic data? • Many possible uses including: – Improvements on rRNA based phylotyping and species diversity measurements – Adding functional information on top of phylogenetic/species diversity information • Most/all possible uses either require or are improved with phylogenetic analysisMonday, February 14, 2011
  84. 84. Example I: Phylotyping with rRNA and other genesMonday, February 14, 2011
  85. 85. Functional Diversity of Proteorhodopsins? Venter et al., 2004Monday, February 14, 2011
  86. 86. Weighted % of Clones 0 0.1250 0.2500 0.3750 0.5000 Al ph ap ro t eo Be b ac ta pr t er ot e ia G ob am ac m t er ap iaMonday, February 14, 2011 ro Ep te si ob lo ac np t er ro ia De t eo lta b ac pr te ot ria eo b C ac ya ter n ob ia ac t er Fi ia rm ic u te Ac s tin ob ac t er C ia hl or ob i C FB Major Phylogenetic Group Sargasso Phylotypes C hl or of le Sp xi iro ch ae te Fu so s De ba in ct er oc ia oc cu s- Eu The ry r ar mu ch s ae C ot re a na rc ha eo ta Shotgun Sequencing Allows Use of Other Markers EFG Venter et al., Science 304: 66-74. 2004 EFTu rRNA RecA RpoB HSP70
  87. 87. Example II: BinningMonday, February 14, 2011
  88. 88. Metagenomics ChallengeMonday, February 14, 2011
  89. 89. Binning challenge A T B U C V D W E X F Y G ZMonday, February 14, 2011
  90. 90. Binning challenge A T B U C V D W E X F Y G Best binning method: reference genomes ZMonday, February 14, 2011
  91. 91. Binning challenge A T B U C V D W E X F Y G Best binning method: reference genomes ZMonday, February 14, 2011
  92. 92. Binning challenge A T B U C V D W E X F Y G No reference genome? What do you do? ZMonday, February 14, 2011
  93. 93. Binning challenge A T B U C V D W E X F Y G No reference genome? What do you do? Z Phylogeny ....Monday, February 14, 2011
  94. 94. Monday, February 14, 2011
  95. 95. No Amino-Acid SynthesisMonday, February 14, 2011
  96. 96. Monday, February 14, 2011
  97. 97. ???????Monday, February 14, 2011
  98. 98. CFB PhylaMonday, February 14, 2011
  99. 99. Sulcia makes amino acids Baumannia makes vitamins and cofactors Wu et al. 2006 PLoS Biology 4: e188.Monday, February 14, 2011
  100. 100. Phylogenomics of Novelty III Knowing What We Don’t KnowMonday, February 14, 2011
  101. 101. Research Topics Variation in Mechanisms of Mechanisms: Origin of New Patterns, Causes Functions and Effects Species EvolutionMonday, February 14, 2011
  102. 102. Research Topics Variation in Mechanisms of Mechanisms: Origin of New Patterns, Causes Functions and Effects Species EvolutionMonday, February 14, 2011
  103. 103. As of 2002Monday, February 14, 2011
  104. 104. As of 2002 Proteobacteria TM6 OS-K • At least 40 Acidobacteria Termite Group OP8 phyla of Nitrospira Bacteroides bacteria Chlorobi Fibrobacteres Marine GroupA WS3 Gemmimonas Firmicutes Fusobacteria Actinobacteria OP9 Cyanobacteria Synergistes Deferribacteres Chrysiogenetes NKB19 Verrucomicrobia Chlamydia OP3 Planctomycetes Spriochaetes Coprothmermobacter OP10 Thermomicrobia Chloroflexi TM7 Deinococcus-Thermus Dictyoglomus Aquificae Thermudesulfobacteria Thermotogae OP1 Based on OP11 Hugenholtz, 2002Monday, February 14, 2011
  105. 105. As of 2002 Proteobacteria TM6 OS-K • At least 40 Acidobacteria Termite Group OP8 phyla of Nitrospira Bacteroides bacteria Chlorobi Fibrobacteres Marine GroupA • Genome WS3 Gemmimonas Firmicutes sequences are Fusobacteria Actinobacteria mostly from OP9 Cyanobacteria Synergistes three phyla Deferribacteres Chrysiogenetes NKB19 Verrucomicrobia Chlamydia OP3 Planctomycetes Spriochaetes Coprothmermobacter OP10 Thermomicrobia Chloroflexi TM7 Deinococcus-Thermus Dictyoglomus Aquificae Thermudesulfobacteria Thermotogae OP1 Based on OP11 Hugenholtz, 2002Monday, February 14, 2011
  106. 106. As of 2002 Proteobacteria TM6 OS-K • At least 40 Acidobacteria Termite Group OP8 phyla of Nitrospira Bacteroides bacteria Chlorobi Fibrobacteres Marine GroupA • Genome WS3 Gemmimonas Firmicutes sequences are Fusobacteria Actinobacteria mostly from OP9 Cyanobacteria Synergistes three phyla Deferribacteres Chrysiogenetes NKB19 • Some other Verrucomicrobia Chlamydia OP3 phyla are Planctomycetes Spriochaetes only sparsely Coprothmermobacter OP10 Thermomicrobia sampled Chloroflexi TM7 Deinococcus-Thermus Dictyoglomus Aquificae Thermudesulfobacteria Thermotogae OP1 Based on OP11 Hugenholtz, 2002Monday, February 14, 2011
  107. 107. As of 2002 Proteobacteria TM6 OS-K • At least 40 Acidobacteria Termite Group OP8 phyla of Nitrospira Bacteroides bacteria Chlorobi Fibrobacteres Marine GroupA • Genome WS3 Gemmimonas Firmicutes sequences are Fusobacteria Actinobacteria mostly from OP9 Cyanobacteria Synergistes three phyla Deferribacteres Chrysiogenetes NKB19 • Some other Verrucomicrobia Chlamydia OP3 phyla are Planctomycetes Spriochaetes only sparsely Coprothmermobacter OP10 Thermomicrobia sampled Chloroflexi TM7 Deinococcus-Thermus Dictyoglomus Aquificae Thermudesulfobacteria Thermotogae OP1 Based on OP11 Hugenholtz, 2002Monday, February 14, 2011
  108. 108. Proteobacteria• NSF-funded TM6 OS-K • At least 40 Tree of Life Acidobacteria Termite Group phyla of OP8 Project Nitrospira Bacteroides bacteria Chlorobi• A genome Fibrobacteres Marine GroupA • Genome WS3 from each of Gemmimonas sequences are Firmicutes eight phyla Fusobacteria mostly from Actinobacteria OP9 Cyanobacteria Synergistes three phyla Deferribacteres Chrysiogenetes NKB19 • Some other Verrucomicrobia Chlamydia OP3 phyla are only Planctomycetes Spriochaetes sparsely Coprothmermobacter OP10 Thermomicrobia sampled Chloroflexi TM7 Deinococcus-Thermus • Solution I: Dictyoglomus Eisen, Ward, Aquificae Thermudesulfobacteria sequence more Robb, Nelson, et Thermotogae phyla OP1 al OP11Monday, February 14, 2011
  109. 109. Monday, February 14, 2011
  110. 110. Proteobacteria• NSF-funded TM6 OS-K • At least 40 Tree of Life Acidobacteria Termite Group phyla of bacteria OP8 Project Nitrospira • Genome Bacteroides• A genome Chlorobi Fibrobacteres sequences are Marine GroupA from each of WS3 Gemmimonas mostly from eight phyla Firmicutes Fusobacteria three phyla Actinobacteria OP9 Cyanobacteria • Some other Synergistes Deferribacteres Chrysiogenetes phyla are only NKB19 Verrucomicrobia sparsely Chlamydia OP3 Planctomycetes sampled Spriochaetes Coprothmermobacter • Still highly OP10 Thermomicrobia Chloroflexi biased in terms TM7 Deinococcus-Thermus Dictyoglomus of the tree AquificaeEisen & Ward, PIs Thermudesulfobacteria Thermotogae OP1 OP11Monday, February 14, 2011
  111. 111. Proteobacteria• NSF-funded TM6 OS-K • At least 40 Tree of Life Acidobacteria Termite Group phyla of bacteria OP8 Project Nitrospira • Genome Bacteroides• A genome Chlorobi Fibrobacteres sequences are Marine GroupA from each of WS3 Gemmimonas mostly from eight phyla Firmicutes Fusobacteria three phyla Actinobacteria OP9 Cyanobacteria • Some other Synergistes Deferribacteres Chrysiogenetes phyla are only NKB19 Verrucomicrobia sparsely Chlamydia OP3 Planctomycetes sampled Spriochaetes Coprothmermobacter • Same trend in OP10 Thermomicrobia Chloroflexi Archaea TM7 Deinococcus-Thermus Dictyoglomus AquificaeEisen & Ward, PIs Thermudesulfobacteria Thermotogae OP1 OP11Monday, February 14, 2011

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