Genomic Evolvability                                  and the Origin of Novelty                                        Jon...
Secret Message Coming …                                        Jonathan A. Eisen                                    U. C. ...
Genomic Evolvability                                  and the Origin of Novelty                                           ...
Eisen Lab - Phylogenomics of Novelty              Origin of New                                              Genome       ...
“Nothing in biology makes sense                                  except in the light of evolution.”                       ...
Origin of Novelty                        • How does novelty originate?                        • What are the constraints o...
Phylogenomic Analysis                        • Evolutionary reconstructions greatly                          improve genom...
Phylogenomic Tales                        • Predicting functions with evolutionary trees                        • Recently...
Phylogenomics I:                                  Predicting Functions with                                     Evolutiona...
SNF2 Family of Proteins (1995)                        • SNF2 family defined by presence of conserved DNA-                 ...
HEPA._E.c                                  NPHCG_42                                  LODE._D.m                            ...
SNF2 Tree and F(x) Prediction                        • Function conserved within but not between                          ...
From Eisen et al.                                  1997 Nature                                  Medicine 3: 1076-10       ...
Blast Search of H. pylori “MutS”                                                                                       Sco...
Phylogenetic Tree of MutS Family                                                                 Aquae                    ...
MutS Subfamilies                                                            M S H 5A q u a e                  M utS 2     ...
Overlaying Functions onto Tree                                                                                            ...
Functional Prediction Using Tree                           M S H 5 - M e io t ic C r o s s in g O v e u t S 2 - U n k n o ...
QuickTimeª and a                                     TIFF (LZW) decompressor                                  are needed t...
Evolutionary Functional Prediction                                        SpeciesMETHOD EVOLUTION                         ...
Phylogenetic Prediction of Function                        • Many powerful and automated similarity based                 ...
Phylogenomics II                                   Recent Evolution       QuickTimeª and a   TIFF (LZW) decompressor      ...
Recent Functional Changes                        • Phylogenomic functional prediction may not work                        ...
Lineage Specific Gene Family                                           Expansions                        • Lineage specifi...
Expansion of MCP Family in V. cholerae                                  NJ                                                ...
Phylogenomics III                                  Uncharacterized genes        QuickTimeª and a                          ...
Non homology functional prediction                        • Many genes have homologs in other species                     ...
Phylogenetic profiling basis                        • Microbial genes are lost rapidly when not                          m...
Non-Homology Predictions:                                    Phylogenetic Profiling                           • Step 1: Se...
Carboxydothermus hydrogenoformans   • Isolated from a Russian hotspring   • Thermophile (grows at 80°C)   • Anaerobic   • ...
Homologs of Sporulation Genes                                                         QuickTimeª and a                    ...
Carboxydothermus sporulates       QuickTimeª and a   TIFF (LZW) decompressorare needed to see this picture.               ...
QuickTimeª and a                                            TIFF (LZW) decompressor                                       ...
QuickTimeª and a   TIFF (LZW) decompressor                                            QuickTimeª and a                    ...
QuickTimeª and a   TIFF (LZW) decompressor                                            QuickTimeª and a                    ...
PG Profiling Works Better Using                                             Orthology       QuickTimeª and a   TIFF (LZW) ...
Phylogenomics IV                                   Acquiring functions       QuickTimeª and a   TIFF (LZW) decompressor   ...
Acquiring functions                        • Sometimes, it is easier to steal, borrow, or                          coopt f...
QuickTimeª and a   TIFF (LZW) decompressor                                            QuickTimeª and a                    ...
Glassy Winged Sharpshooter                                                   • Obligate xylem feeder                      ...
Xylem and Phloem                                                     From                                                 ...
Sharpshooter Shotgun Sequencing                                                                shotgun                    ...
QuickTimeª and a   TIFF (LZW) decompressor                                            QuickTimeª and a                    ...
QuickTimeª and a   TIFF (LZW) decompressor                                            QuickTimeª and a                    ...
1                                            600,000                                                                      ...
Baumannia is a Vitamin and                                  Cofactor Producing Machine                                    ...
No Amino-Acid Synthesis                                                            Wu et al.                              ...
QuickTimeª and a   TIFF (LZW) decompressor                                            QuickTimeª and a                    ...
???????       QuickTimeª and a   TIFF (LZW) decompressor                                                      QuickTimeª a...
Commonly Used Binning Methods                                       Did not Work Well                        • Assembly   ...
Host Sequence?       QuickTimeª and a   TIFF (LZW) decompressor                                                           ...
CFB Phyla       QuickTimeª and a   TIFF (LZW) decompressor                                                        QuickTim...
QuickTimeª and a   TIFF (LZW) decompressor                                  Wu et al. 2006 PLoS Biology 4: e188.          ...
Binning by Phylogeny                        • Four main “phylotypes”                                  –   Gamma proteobact...
Binning by Phylogeny                        • Four main “phylotypes”                                  –   Gamma proteobact...
Essential Amino Acid Synthesis       QuickTimeª and a                                                            Wu et al....
Co-Symbiosis?                                                  Wu et al.                                                  ...
Model for Metagenomics              A                                            T              B                         ...
Functional Diversity of Proteorhodopsins?       QuickTimeª and a   TIFF (LZW) decompressorare needed to see this picture. ...
Phylogenomics V                                  Knowing What We Do Not Know       QuickTimeª and a   TIFF (LZW) decompres...
rRNA Tree of Life                                              QuickTimeª and a                                         TI...
The Tree is not Happy                                              QuickTimeª and a                                       ...
As of 2002                         Proteobacteria                                    TM6                                  ...
As of 2002                        Proteobacteria                                   TM6                                   O...
As of 2002                        Proteobacteria                                   TM6                                   O...
As of 2002                        Proteobacteria                                   TM6                                   O...
Proteobacteria• Eisen-Ward                        TM6                    • At least 40                                    ...
Proteobacteria• JGI -                                                               TM6                    • At least 40  ...
QuickTimeª and a                                     TIFF (LZW) decompressor                                  are needed t...
Genomic Evolvability and the Origin of Novelty - talk for ASMGM 2008 by @phylogenomics
Genomic Evolvability and the Origin of Novelty - talk for ASMGM 2008 by @phylogenomics
Genomic Evolvability and the Origin of Novelty - talk for ASMGM 2008 by @phylogenomics
Genomic Evolvability and the Origin of Novelty - talk for ASMGM 2008 by @phylogenomics
Genomic Evolvability and the Origin of Novelty - talk for ASMGM 2008 by @phylogenomics
Genomic Evolvability and the Origin of Novelty - talk for ASMGM 2008 by @phylogenomics
Genomic Evolvability and the Origin of Novelty - talk for ASMGM 2008 by @phylogenomics
Genomic Evolvability and the Origin of Novelty - talk for ASMGM 2008 by @phylogenomics
Genomic Evolvability and the Origin of Novelty - talk for ASMGM 2008 by @phylogenomics
Genomic Evolvability and the Origin of Novelty - talk for ASMGM 2008 by @phylogenomics
Genomic Evolvability and the Origin of Novelty - talk for ASMGM 2008 by @phylogenomics
Genomic Evolvability and the Origin of Novelty - talk for ASMGM 2008 by @phylogenomics
Genomic Evolvability and the Origin of Novelty - talk for ASMGM 2008 by @phylogenomics
Genomic Evolvability and the Origin of Novelty - talk for ASMGM 2008 by @phylogenomics
Genomic Evolvability and the Origin of Novelty - talk for ASMGM 2008 by @phylogenomics
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Genomic Evolvability and the Origin of Novelty - talk for ASMGM 2008 by @phylogenomics

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  • Research in my lab focuses on the mechanisms through which novelty (e.g., new functions and new processes) originates in microorganisms. In particular we make use of phylogenomic analysis (combining evolutionary reconstructions with genome sequence analyses) to study these mechanisms. The mechanisms in which I am include those that allow an existing gene to change its function (e.g., gene duplication and divergence; domain swapping) and that allow organisms to acquire functions from other species (e.g., lateral transfer and symbioses). In addition, my work examines how differences in DNA repair, replication, and recombination processes influence the ability of organisms to generate novelty. In my talk I will discuss our recent work in this area, first focusing on model cultured organisms whose genomes we are sequencing or have recently sequenced (e.g., Tetrahymena thermophila, Haloferax volcanii). Then I will discuss how phylogenomic approaches can be used to study the origin of novelty in uncultured species (e.g., symbionts and microbial communities). Finally, I will discuss our plans for future research on the origin of novelty.
  • Research in my lab focuses on the mechanisms through which novelty (e.g., new functions and new processes) originates in microorganisms. In particular we make use of phylogenomic analysis (combining evolutionary reconstructions with genome sequence analyses) to study these mechanisms. The mechanisms in which I am include those that allow an existing gene to change its function (e.g., gene duplication and divergence; domain swapping) and that allow organisms to acquire functions from other species (e.g., lateral transfer and symbioses). In addition, my work examines how differences in DNA repair, replication, and recombination processes influence the ability of organisms to generate novelty. In my talk I will discuss our recent work in this area, first focusing on model cultured organisms whose genomes we are sequencing or have recently sequenced (e.g., Tetrahymena thermophila, Haloferax volcanii). Then I will discuss how phylogenomic approaches can be used to study the origin of novelty in uncultured species (e.g., symbionts and microbial communities). Finally, I will discuss our plans for future research on the origin of novelty.
  • Research in my lab focuses on the mechanisms through which novelty (e.g., new functions and new processes) originates in microorganisms. In particular we make use of phylogenomic analysis (combining evolutionary reconstructions with genome sequence analyses) to study these mechanisms. The mechanisms in which I am include those that allow an existing gene to change its function (e.g., gene duplication and divergence; domain swapping) and that allow organisms to acquire functions from other species (e.g., lateral transfer and symbioses). In addition, my work examines how differences in DNA repair, replication, and recombination processes influence the ability of organisms to generate novelty. In my talk I will discuss our recent work in this area, first focusing on model cultured organisms whose genomes we are sequencing or have recently sequenced (e.g., Tetrahymena thermophila, Haloferax volcanii). Then I will discuss how phylogenomic approaches can be used to study the origin of novelty in uncultured species (e.g., symbionts and microbial communities). Finally, I will discuss our plans for future research on the origin of novelty.
  • My major research interests
  • Genomic Evolvability and the Origin of Novelty - talk for ASMGM 2008 by @phylogenomics

    1. 1. Genomic Evolvability and the Origin of Novelty Jonathan A. Eisen U. C. Davis Genome Center ASM General Meeting Boston, MA June 4, 2008 QuickTimeª and a QuickTimeª and a TIFF (Uncompressed) decompressor TIFF (LZW) decompressor are needed to see this picture.are needed to see this picture.
    2. 2. Secret Message Coming … Jonathan A. Eisen U. C. Davis Genome Center ASM General Meeting Boston, MA June 4, 2008 QuickTimeª and a QuickTimeª and a TIFF (Uncompressed) decompressor TIFF (LZW) decompressor are needed to see this picture.are needed to see this picture.
    3. 3. Genomic Evolvability and the Origin of Novelty Jonathan A. Eisen QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture. U. C. Davis Genome Center ASM General Meeting Boston, MA June 4, 2008 QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    4. 4. Eisen Lab - Phylogenomics of Novelty Origin of New Genome Functions and Dynamics Processes •Evolvability •New genes •Repair and •Changes in old genes recombination processes •Changes in pathways •Intragenomic variation Species Evolution •Phylogenetic history •Vertical vs. horizontal descent •Needed to track gain/loss of QuickTimeª and a TIFF (LZW) decompressorare needed to see this picture. processes, infer convergence QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.
    5. 5. “Nothing in biology makes sense except in the light of evolution.” T. H. Dobzhansky (1973) QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    6. 6. Origin of Novelty • How does novelty originate? • What are the constraints on evolvability? • What leads to variation within the genome and within and between species in evolvability • This information helps interpret the past, understand the present and (maybe) predict the future QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    7. 7. Phylogenomic Analysis • Evolutionary reconstructions greatly improve genome analyses • Genome analysis greatly improves evolutionary reconstructions • There is a feedback loop such that these should be integrated QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    8. 8. Phylogenomic Tales • Predicting functions with evolutionary trees • Recently evolved new functions • Uncharacterized genes • Stealing functions • Knowing what we do not know QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    9. 9. Phylogenomics I: Predicting Functions with Evolutionary Trees QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    10. 10. SNF2 Family of Proteins (1995) • SNF2 family defined by presence of conserved DNA- dependent ATPase domain Bork and Koonin 1993 • 100s of proteins • Diversity of functions: – transcriptional activation (SNF2) – transcriptional repression (MOT1) – Recombination (RAD54) QuickTimeª and a TIFF (LZW) decompressor – transcription-coupled repair (CSB) are needed to see this picture. – post-replication repair (RAD5) – chromosome segregation (lodestar) – Many with unknown functions • Some species have 15+ representatives QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    11. 11. HEPA._E.c NPHCG_42 LODE._D.m MOT1_S.c SNF2_S.c STH1_S.c BRG1_M.m BRG1_H.s BRM_H.s BRM_D.m SNF2L_H.s F37A4_C.e DNRPPX_S.p NUCP_M.m NUCP_H.s RAD26_S.c ERCC6_H.s SYGP4_S.c CHD1_M.m ETL1_M.m ISWI_D.m YB95_S.c RAD16_S.c HIP116A_H.s RAD8_S.p RAD5_S.c RAD54_S.c YB53_S.c YA19_S.c LODE RAD16 RAD54 CSB ETL1 CHD1 SNF2L SNF2 Evolution of the SNF2 Family of Proteins QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    12. 12. SNF2 Tree and F(x) Prediction • Function conserved within but not between subfamilies/orthology groups • Therefore, assignment of genes to subfamilies can be used to predict functions of unknowns • Grouping into subfamilies helps identify motifs conserved within groups • Phylogeny recovers subfamilies better than similarity searches QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    13. 13. From Eisen et al. 1997 Nature Medicine 3: 1076-10 QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    14. 14. Blast Search of H. pylori “MutS” Score ESequences producing significant alignments: (bits) Valuesp|P73625|MUTS_SYNY3 DNA MISMATCH REPAIR PROTEIN 117 3e25 -sp|P74926|MUTS_THEMA DNA MISMATCH REPAIR PROTEIN 69 1e10 -sp|P44834|MUTS_HAEIN DNA MISMATCH REPAIR PROTEIN 64 3e09 -sp|P10339|MUTS_SALTY DNA MISMATCH REPAIR PROTEIN 62 2e08 -sp|O66652|MUTS_AQUAE DNA MISMATCH REPAIR PROTEIN 57 4e07 -sp|P23909|MUTS_ECOLI DNA MISMATCH REPAIR PROTEIN 57 4e07 - • 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 QuickTimeª and a TIFF (LZW) decompressorare needed to see this picture. Based on Eisen et al. 1997 Nature Medicine 3: 1076-1078. QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.
    15. 15. Phylogenetic Tree of MutS Family Aquae Strpy Bacsu Synsp Deira Helpy Yeast Human Borbu Metth Celeg mSaco Yeast Human Yeast Mouse Arath Celeg Human Arath Human Mouse Spombe Fly Yeast Xenla Rat Mouse Yeast Human Spombe Yeast Neucr Arath Aquae Trepa Chltr DeiraTheaq Thema BacsuBorbu Based on Eisen, SynspStrpy 1998 Nucl Acids QuickTimeª and a Ecoli TIFF (LZW) decompressor Res 26: 4291-4300. QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture. Neigo
    16. 16. MutS Subfamilies M S H 5A q u a e M utS 2 S trB y c S uns p p a s y D e ir a H e lp y Ye a s t Huma n B orbu M e tth C e le g mS a c o MS H6 Ye a s t Huma n Mous e A ra th Ye a s t MS H4 C e le g Huma n A ra th Huma n MS H3 Mous e F ly S pombe Ye a s t X e n la Rat Mous e Ye a s t Huma n MS H1 S pombe Ye a s t MS H2 Neuc r A ra th Aquae Tre p a C h lt r D e ir a e a q Th B a c s u rbu Bo Th e m a S y n sSpt r p y E c o li N e ig o Based on Eisen, 1998 Nucl Acids QuickTimeª and a M utS 1 TIFF (LZW) decompressor Res 26: 4291-4300. QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    17. 17. Overlaying Functions onto Tree M utS 2 Aquae MS H5 S t rB y c S yn s p pa su D e ir a H e lp y Ye a s t Huma n B orbu M e tth C e le g MS H6 mS a c o Ye a s t Huma n Mous e A ra th MS H4 Ye a s t C e le g Huma n A ra th Huma n MS H3 Mous e S pombe F ly Ye a s t X e n la Rat Mous e Ye a s t Huma n M S H 1 pombe S Ye a s t MS H2 Neuc r A ra th Aquae Tre p a C h lt r D e ir a e a q Th B a c s u rbu Bo Th e m a S y n sSpt r p y Based on Eisen, E c o li N e ig o 1998 Nucl Acids M utS 1 QuickTimeª and a TIFF (LZW) decompressor Res 26: 4291-4300. QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    18. 18. Functional Prediction Using Tree M S H 5 - M e io t ic C r o s s in g O v e u t S 2 - U n k n o w n F u n c t io n s M r Aquae S t rB y c S yn s p pa su D e ir a H e lp y Ye a s t Huma n B orbu M e tth C e le g M S H 6 - N u c le a r mS a c o R e p a ir Ye a s t O f M is m a t c h e s Huma n M S H 4 - M e io t ic C r o s s in g Mous e Y e a sO v e r t A ra th C e le g Huma n A ra thM S H 3 - N u c le a r Huma n Mous eR e p a ir O f L o o p s o m b e S p F ly Ye a s t X e n la Rat M oM s eH 2 - E u k a r y o t i c N u c l e a r u S Ye a s t H u m ai n m a t c h a n d L o o p R e p a i r M sMS H1 S pombe Ye a s tM it o c h o n d r ia l Neuc r A ra thR e p a ir Aquae Tre p a C h lt r D e ir a e a q Th B a c s u rbu Bo Th e m a S y n sSpt r p y E c o li Based on Eisen, N e ig o QuickTimeª and a 1998 Nucl Acids TIFF (LZW) decompressor M u t S 1 - B a c t e r ia l M is m a t c h a n d L o o p R e p a ir Res 26: 4291-4300. QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture. are needed to see this picture.
    19. 19. QuickTimeª and a TIFF (LZW) decompressor are needed to see this picture. QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    20. 20. Evolutionary Functional Prediction SpeciesMETHOD EVOLUTION Duplication?SEQUENCES 5 IDENTIFY HOMOLOGS 4B EXAMPLE A B 3A CALCULATE GENE KNOWN 2CHOOSE GENE(S) OF FUNCTION 1ALIGNINFER LIKELY INTEREST 1ACTUAL 3EXAMPLE Ambiguous Duplication 1A 3B 2B 1B 3A 2A 6 2 OVERLAY TREE (ASSUMED TO BE OFONTO TREE OF GENE(S) UNKNOWN) FUNCTIONS INTEREST Based on Eisen, 1998 Genome QuickTimeª and a TIFF (LZW) decompressor Res 8: 163-167. QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    21. 21. Phylogenetic Prediction of Function • Many powerful and automated similarity based methods for assigning genes to protein families – COGs – PFAM HMM searches • Some limitations of similarity based methods can be overcome by phylogenetic approaches • Automated methods now available – Sean Eddy – Steven Brenner – Kimmen Sjölander • But … QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    22. 22. Phylogenomics II Recent Evolution QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    23. 23. Recent Functional Changes • Phylogenomic functional prediction may not work well for very newly evolved functions • Can we use understanding of origin of novelty to better understand these cases? • Screen genomes for genes that have changed recently – Pseudogenes and gene loss – Contingency Loci – Acquisition (e.g., LGT) – Unusual dS/dN ratios – Rapid evolutionary rates – Duplication and divergence QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    24. 24. Lineage Specific Gene Family Expansions • Lineage specific expansions frequently associated with adaptive evolution • Can screen genomes for such expansions by looking for genes more closely related to other genes in the genome than to genes from other species QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    25. 25. Expansion of MCP Family in V. cholerae NJ V. choleraeVC 12 05 V. chole raeV C 03 4 A1 V. choleraeVC 97 4A0 ** V. choleraeVC 06 8A0 * V. chole rae C 25 V 08 V. choleraeV C 82 02 V. chole rae C 90 6 V A0 V. chole raeV C 979 A0 V. chole rae C 05 6 V A1 V. choleraeV C 43 16 V. chole rae C 61 V 21 ** V. choleraeVC 92 3 A0 ** V. choleraeV C 14 05 V. choleraeVC 68 18 V. chole raeV C 77 3 A0 V. choleraeV C 13 13 V. chole raeV C 5918 V. choleraeV C 13 14 V. chole rae C 26 8 V A0 ** V. chole raeV C 65 8 A0 V. choleraeV C 05 14 * V. cholerae 12 98 VC V. choleraeV C 4812 V. chole raeV C 86 4 A0 V. choleraeVC 17 6 A0 ** V chole raeV C 22 0 . A0 V. choleraeVC 89 12 ** V. choleraeVC 06 9A1 V. choleraeV C 39 24 V. choleraeVC 67 19 V. chole rae C 031 V A0 V. choleraeV C 98 18 V. chole rae C 663 V A0 V. choleraeVC 988 A0 V. chole raeV C 16 02 * V. chole raeV C 49 04 V. chole rae C 00 8 V A0 V. choleraeVC 06 14 V. chole raeV C 35 15 V. choleraeV C 40 08 B.subtilis gi2633766 Synechocystis sp. gi1001299 * Synechocystis sp. gi1001300 * Synechocystis sp. gi1652276 * Synechocystis sp. gi1652103 H.pylori gi2313716 ** H.pylori9Cj1190c C.jejuni 9 gi4155097 ** C.jejuni Cj1110c A.fulgidus gi2649560 A.fulgidus gi2649548 ** B.subtilis gi2634254 B.subtilis gi2632630 B.subtilis gi2635607 B.subtilis gi2635608 ** B.subtilis gi2635609 ** ** B.subtilis gi2635610 B.subtilis gi2635882 E.coli gi1788195 ** E.coli gi2367378 * E.coli gi1788194 E.coli gi1787690 V. choleraeV C 092 A1 V. choleraeVC 98 00 E.coli gi1789453 H.pylori gi2313186 H.pylori99 gi4154603 ** C.jejuni Cj0144 C.jejuni Cj1564 ** C.jejuni Cj0262c ** C.jejuni Cj1506c H.pylori gi2313163 * H.pylori99 gi4154575 ** H.pylori gi2313179 ** ** H.pylori99 gi4154599 C.jejuni Cj0019c C.jejuni Cj0951c C.jejuni Cj0246c B.subtilis gi2633374 T.maritima TM0014 V. choleraeV C 03 14 V. chole rae C 08 8 V A1 T.pallidum gi3322777 ** T.pallidum gi3322939 ** T.pallidum gi3322938 B.burgdorferi gi2688522 T.pallidum gi3322296 B.burgdorferi gi2688521 * T.maritima TM0429 ** T.maritima TM0918 ** T.maritima TM0023 * T.maritima TM1428 T.maritima TM1143 T.maritima TM1146 P.abyssi PAB1308 ** P.horikoshii gi3256846 ** P.abyssi PAB1336 P.horikoshii gi3256896 ** P.abyssi PAB2066 ** ** ** P.horikoshii gi3258290 * P.abyssi PAB1026 ** P.horikoshii gi3256884 ** D.radiodurans DRA00354 D.radiodurans DRA0353 D.radiodurans DRA0352 Based on Heidelberg et al. ** 2000 Nature 406:477-483. ** V. choleraeVC 94 13 QuickTimeª and a P.abyssi PAB1189 TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor ** P.horikoshii gi3258414 are needed to see this picture.are needed to see this picture. B.burgdorferi gi2688621 M.tuberculosis gi1666149 V. choleraeV C 22 06
    26. 26. Phylogenomics III Uncharacterized genes QuickTimeª and a QuickTimeª and a TIFF (Uncompressed) decompressor TIFF (LZW) decompressor are needed to see this picture.are needed to see this picture.
    27. 27. Non homology functional prediction • Many genes have homologs in other species but no homologs have ever been studied experimentally • Non-homology methods can make functional predictions for these QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    28. 28. Phylogenetic profiling basis • 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 functions QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    29. 29. 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) QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    30. 30. 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. ) QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    31. 31. Homologs of Sporulation Genes QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture. Wu et al. 2005 PLoS QuickTimeª and a TIFF (LZW) decompressor Genetics 1: e65. QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    32. 32. Carboxydothermus sporulates QuickTimeª and a TIFF (LZW) decompressorare needed to see this picture. Wu et al. 2005 PLoS Genetics 1: e65. QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.
    33. 33. QuickTimeª and a TIFF (LZW) decompressor are needed to see this picture. QuickTimeª and a TIFF (LZW) decompressorare needed to see this picture. Wu et al. 2005 PLoS Genetics 1: e65. QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.
    34. 34. QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    35. 35. QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    36. 36. PG Profiling Works Better Using Orthology QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    37. 37. Phylogenomics IV Acquiring functions QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    38. 38. Acquiring functions • Sometimes, it is easier to steal, borrow, or coopt functions rather than evolve them anew • Two main pathways for this – Lateral gene transfer – Symbioses QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    39. 39. QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    40. 40. Glassy Winged Sharpshooter • Obligate xylem feeder • Can transmit Pierce’s Disease agent • Potential bioterror agent • Needs to get amino- acids and other nutrients from symbionts like aphids QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    41. 41. Xylem and Phloem From Lodish et al. 2000 QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    42. 42. Sharpshooter Shotgun Sequencing shotgun Collaboration with Nancy Wu et al. 2006 PLoS Biology 4: e188. Moran’s lab QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    43. 43. QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    44. 44. QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    45. 45. 1 600,000 100,000 500,000 200,000 400,000 300,000 QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    46. 46. Baumannia is a Vitamin and Cofactor Producing Machine Wu et al. 2006 PLoS QuickTimeª and a Biology 4: e TIFF (LZW) decompressor . QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    47. 47. No Amino-Acid Synthesis Wu et al. 2006 PLoS QuickTimeª and a Biology 4: e TIFF (LZW) decompressor . QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    48. 48. QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    49. 49. ??????? QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    50. 50. Commonly Used Binning Methods Did not Work Well • Assembly – Only Baumannia generated good contigs • Depth of coverage – Everything else 0-1X coverage • Nucleotide composition – No detectible peaks in any vector we looked at QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    51. 51. Host Sequence? QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    52. 52. CFB Phyla QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    53. 53. QuickTimeª and a TIFF (LZW) decompressor Wu et al. 2006 PLoS Biology 4: e188. QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    54. 54. Binning by Phylogeny • Four main “phylotypes” – Gamma proteobacteria (Baumannia) – Arthropoda (sharpshooter) – Bacteroidetes (Sulcia) – Alpha-proteobacteria (Wolbachia) QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    55. 55. Binning by Phylogeny • Four main “phylotypes” – Gamma proteobacteria (Baumannia) – Arthropoda (sharpshooter) – Bacteroidetes (Sulcia) - only a.a. genes here – Alpha-proteobacteria (Wolbachia) QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    56. 56. Essential Amino Acid Synthesis QuickTimeª and a Wu et al. 2006 PLoS TIFF (LZW) decompressor Biology 4: e188. QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    57. 57. Co-Symbiosis? Wu et al. 2006 PLoS QuickTimeª and a Biology 4: e TIFF (LZW) decompressor . QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    58. 58. Model for Metagenomics A T B U C V D W E X F Y G Z QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    59. 59. Functional Diversity of Proteorhodopsins? QuickTimeª and a TIFF (LZW) decompressorare needed to see this picture. Venter et al., 2004 QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.
    60. 60. Phylogenomics V Knowing What We Do Not Know QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    61. 61. rRNA Tree of Life QuickTimeª and a TIFF (LZW) decompressor are needed to see this picture. QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    62. 62. The Tree is not Happy QuickTimeª and a TIFF (LZW) decompressor are needed to see this picture. QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    63. 63. 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 QuickTimeª and a OP11 TIFF (LZW) decompressor Hugenholtz, 2002 QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture. are needed to see this picture.
    64. 64. 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 three phyla Synergistes Deferribacteres Chrysiogenetes NKB19 Verrucomicrobia Chlamydia OP3 Planctomycetes Spriochaetes Coprothmermobacter OP10 Thermomicrobia Chloroflexi TM7 Deinococcus-Thermus Dictyoglomus Aquificae Thermudesulfobacteria Thermotogae QuickTimeª and a OP1 Based on TIFF (LZW) decompressor OP11 Hugenholtz, 2002 QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    65. 65. 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 three phyla Synergistes Deferribacteres Chrysiogenetes • Some other NKB19 Verrucomicrobia Chlamydia phyla are OP3 Planctomycetes Spriochaetes only sparsely Coprothmermobacter OP10 sampled Thermomicrobia Chloroflexi TM7 Deinococcus-Thermus Dictyoglomus Aquificae Thermudesulfobacteria Thermotogae QuickTimeª and a OP1 Based on TIFF (LZW) decompressor OP11 Hugenholtz, 2002 QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    66. 66. 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 three phyla Synergistes Deferribacteres Chrysiogenetes • Some other NKB19 Verrucomicrobia Chlamydia phyla are OP3 Planctomycetes Spriochaetes only sparsely Coprothmermobacter OP10 sampled Thermomicrobia Chloroflexi TM7 • Same trend in Deinococcus-Thermus Dictyoglomus Aquificae Archaea, Thermudesulfobacteria QuickTimeª and a Thermotogae OP1 Eukaryotes Based on TIFF (LZW) decompressor OP11 Hugenholtz, 2002 QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
    67. 67. Proteobacteria• Eisen-Ward TM6 • At least 40 OS-K NSF Tree of Acidobacteria Termite Group phyla of OP8 Life 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 three phyla Synergistes Deferribacteres Chrysiogenetes • Some other NKB19 Verrucomicrobia Chlamydia phyla are only OP3 Planctomycetes Spriochaetes sparsely Coprothmermobacter OP10 sampled ThermomicrobiaBased on Chloroflexi TM7 • Solution I:Hugenholtz, Deinococcus-Thermus2002 Dictyoglomus Aquificae sequence more Thermudesulfobacteria QuickTimeª and a Thermotogae OP1 phyla TIFF (LZW) decompressor are needed to see this picture. OP11 QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.
    68. 68. Proteobacteria• JGI - TM6 • At least 40 OS-K Genomic Acidobacteria Termite Group phyla of OP8 Encyclopedia Nitrospira Bacteroides bacteria of Bacteria Chlorobi Fibrobacteres • Genome Marine GroupA and Archaea WS3 Gemmimonas sequences are Firmicutes Fusobacteria Actinobacteria mostly from OP9 Cyanobacteria three phyla Synergistes QuickTimeª and a TIFF (LZW) decompressor are needed to see this picture. Deferribacteres Chrysiogenetes • Some other NKB19 Verrucomicrobia Chlamydia phyla are only OP3 Planctomycetes Spriochaetes sparsely Coprothmermobacter OP10 sampled ThermomicrobiaBased on Chloroflexi TM7 • Solution II: FillHugenholtz, Deinococcus-Thermus2002 Dictyoglomus Aquificae in Phyla Thermudesulfobacteria Thermotogae OP1 QuickTimeª and a TIFF (LZW) decompressor are needed to see this picture. OP11 QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.
    69. 69. QuickTimeª and a TIFF (LZW) decompressor are needed to see this picture. QuickTimeª and a TIFF (LZW) decompressor QuickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture.are needed to see this picture.
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