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Comparative genomics of fung: studying adaptation through gene family evolution

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March 2007 presentation at Fungal Genetics conference

March 2007 presentation at Fungal Genetics conference

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  • 1. Comparative genomics of fungi: studying adaptation through gene family evolution Jason Stajich University of California, Berkeley
  • 2. Gene family evolution • How do fungi adapt to a niche? How do they acquire new functions and new genes? • Neofunctionalization • Horizontal Transfer • Duplication and innovation • Are genome-wide patterns of duplication or loss useful to understand adaptation?
  • 3. Gene family sizes follow power law distribution single copy genes PRP8 (splicing) CDC48 (cell cycle ATPase) Multicopy genes Sugar transporters P450 Enzymes
  • 4. Models of gene family evolution • Need a Null model for comparison of gene family size • Birth-Death model for gene family size evolution • CAFE: Computational Analysis of Family Evolution • Compare observed to expected patterns of family size Hahn et al, Genome Res 2005 Demuth et al, PLoS One 2006
  • 5. Case study: mammals 6% difference Demuth JP, De Bie T, Stajich JE, Cristiani N, Hahn MW. PLoS One 2006
  • 6. Methods: Gene families • Functional Annotation “Free” • Build gene families from protein sequence similarity (FASTP), clustered with MCL • Identify families that are unusually large or small with CAFE • Build gene trees to validate and study mode and tempo of duplication. • Protein Domain distribution • Pfam domain counts
  • 7. FASTA Family count all-vs-all 10 1 2 14 18 2 Species 7 1 1 + MCL 6 1 12 6 1 8 3 1 1 Gene families CAFE Family 1 P < 0.001 Branch A Family 2 P < 0.001 Branch B Branch Family 3 P=0.02 C,E Family 4 P=0.03 Branch D
  • 8. Phylogeny of sequenced fungi Basidiomycota Eurotiomycetes Fitzpatrick DA, Logue ME, Stajich JE, Butler G. BMC Genomics 2006
  • 9. Coccidioides: Evolution of a pathogen Short Life Granuloma D octorfungus. com M. McGinnis Spherule Long Life Endospores
  • 10. Gene Family Evolution in the Onygenales ML phylogeny from 1148 concatenated genes 46890 unambiguous AA sites after removing gaps.
  • 11. Onygenales Family expansions Peptidase Keritinase M35 2 1 0 1 3 3 4 2 3 2 3 2 7 13 7 14 4 13 2 2
  • 12. Keratinases in Onygenales SignalP Subtilisin_N • Onygenales are Keratinophilic • Domains: Peptidase S8, Subtilisin domains • Large expansion of putative keratinases in Onygenales
  • 13. Keratinase expansion in Onygenales 13/14 copies in Coccidioides 1 in Histoplasma Expansion of 7
  • 14. Metalloproteinase expansion MEP1 is a previously described Virulence factor (Hung et al. 2005) MEP4 MEP8 MEP6 MEP5 MEP3 MEP7 MEP2
  • 15. Family contractions in Onygenales Cellulase Domain Cellulase Cutinase Binding Tannase 1 3 7 18 1 0 2 0 5 5 13 17 11 5 11 3 6 8 16 15 6 4 15 7 0 1 2 0 0 1 2 0 0 1 2 0 0 2 3 0
  • 16. Carbohydrate metabolism • Domains absent or contracted in Onygenales fungi • Tannase, Cutinase • Pectin Lyase, Cellulase, Cellulase Binding Domain, Pectinesterase • Alpha-L-arabinofuranosidase • Glycosyl hydrolase • HET domain
  • 17. Summary • Onygenales fungi have lost many domains relating to saprophytic growth on plant matter • Few expansions, but at least one family is related to a known virulence factor • MEP genes are good Cocci specific expansion
  • 18. Basidiomycota changes C.neoformans P.chrysosporium C.cinereus U.maydis
  • 19. P450 CYP64 P450 enzymes involved in synthesis and cleavage of chemical bonds. Drug metabolism in animals. CYP64: Step in Aspergillus spp aflatoxin pathway P. chrysosporium implicated in lignin and hydrocarbon degradation.
  • 20. CYP64 was from independent duplication C. cinereus expansion P. chrysosporium expansion Mario Cervini Tom Volk
  • 21. Local duplications created CYP64 expansion
  • 22. Interpretation of CYP64 expansion Million years ago
  • 23. Hydrophobin Family P.chr C.cin C.neo U.may 21 33 0 2 • Self assembling proteins involved in fungal cell wall • Part of what makes a mushroom • 8 Cysteine residues critical to function • Help spores stay airborne resisting water
  • 24. Local Duplications P. chrysosporium C. cinereus
  • 25. Summary •Local duplications are a major mode of family expansion in two Homobasidiomycetes •Independent expansion of families •Convergent evolution •High gene turnover in some families?
  • 26. Bruns TD. Nature 2006 James et al. Nature 2006
  • 27. Chytrid family changes • Expansions • More Polysaccharide deacyetalase (2x) and Chitin binding domains than most fungi • 12 Chitin synthases, but R.oryzae has 23+, Most other fungi have 1-5. • Bd Contractions or small families in fungal ancestor • No Glucan synthase (FKS1) homolog. • Few Sugar transporters and Major Facilitor Superfamily. No Acetate transporter. • Of 9 P450 genes, 2 pairs are adjacent.
  • 28. Discussion • Gene content differences not just orthologous genes need to be considered when describing species divergence. • Losses may be more informative in some clades. • Family size change can be a useful starting point for comparing species. • Models that incorporate phylogenetic context are critical.
  • 29. Acknowledgments Indiana University Sequencing Centers Matthew Hahn Miller Institute for Basic Research in Science FGI, Broad Institute DOE - JGI UC Berkeley TIGR Thomas Sharpton Stanford GTC John Taylor Baylor College of Medicine Duke University Fred Dietrich

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