Comparative genomics of fung: studying adaptation through gene family evolution

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March 2007 presentation at Fungal Genetics conference

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Comparative genomics of fung: studying adaptation through gene family evolution

  1. 1. Comparative genomics of fungi: studying adaptation through gene family evolution Jason Stajich University of California, Berkeley
  2. 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. 3. Gene family sizes follow power law distribution single copy genes PRP8 (splicing) CDC48 (cell cycle ATPase) Multicopy genes Sugar transporters P450 Enzymes
  4. 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. 5. Case study: mammals 6% difference Demuth JP, De Bie T, Stajich JE, Cristiani N, Hahn MW. PLoS One 2006
  6. 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. 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. 8. Phylogeny of sequenced fungi Basidiomycota Eurotiomycetes Fitzpatrick DA, Logue ME, Stajich JE, Butler G. BMC Genomics 2006
  9. 9. Coccidioides: Evolution of a pathogen Short Life Granuloma D octorfungus. com M. McGinnis Spherule Long Life Endospores
  10. 10. Gene Family Evolution in the Onygenales ML phylogeny from 1148 concatenated genes 46890 unambiguous AA sites after removing gaps.
  11. 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. 12. Keratinases in Onygenales SignalP Subtilisin_N • Onygenales are Keratinophilic • Domains: Peptidase S8, Subtilisin domains • Large expansion of putative keratinases in Onygenales
  13. 13. Keratinase expansion in Onygenales 13/14 copies in Coccidioides 1 in Histoplasma Expansion of 7
  14. 14. Metalloproteinase expansion MEP1 is a previously described Virulence factor (Hung et al. 2005) MEP4 MEP8 MEP6 MEP5 MEP3 MEP7 MEP2
  15. 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. 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. 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. 18. Basidiomycota changes C.neoformans P.chrysosporium C.cinereus U.maydis
  19. 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. 20. CYP64 was from independent duplication C. cinereus expansion P. chrysosporium expansion Mario Cervini Tom Volk
  21. 21. Local duplications created CYP64 expansion
  22. 22. Interpretation of CYP64 expansion Million years ago
  23. 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. 24. Local Duplications P. chrysosporium C. cinereus
  25. 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. 26. Bruns TD. Nature 2006 James et al. Nature 2006
  27. 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. 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. 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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