comparative genomics of fung: studying adaptation through gene family evolution
DESCRIPTION
March 2007 presentation at Fungal Genetics conferenceTRANSCRIPT
Comparative genomicsof fungi: studying
adaptation throughgene family evolution
Jason StajichUniversity of California, Berkeley
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 duplicationor loss useful to understand adaptation?
Gene family sizes followpower law distribution
Multicopy genesSugar transporters
P450 Enzymes
single copy genesPRP8 (splicing)
CDC48 (cell cycle ATPase)
Models of gene familyevolution
• Need a Null model for comparison of genefamily size
• Birth-Death model for gene family sizeevolution
• CAFE: Computational Analysis of FamilyEvolution
• Compare observed to expected patternsof family size
Hahn et al, Genome Res 2005Demuth et al, PLoS One 2006
Case study: mammals
Demuth JP, De Bie T, Stajich JE, Cristiani N, Hahn MW. PLoS One 2006
6%difference
Methods: Gene families• Functional Annotation “Free”
• Build gene families from protein sequencesimilarity (FASTP), clustered with MCL
• Identify families that are unusually large or smallwith CAFE
• Build gene trees to validate and study mode andtempo of duplication.
• Protein Domain distribution
• Pfam domain counts
FASTAall-vs-all
MCL
Gene families
CAFE
Family 1 P < 0.001 Branch A
Family 2 P < 0.001 Branch B
Family 3 P=0.02 BranchC,E
Family 4 P=0.03 Branch D
10 1 2
14 18 2
7 1 1
6 1 12
6 1 8
3 1 1
+
Family count
Spec
ies
Phylogeny of sequenced fungi
Fitzpatrick DA, Logue ME,Stajich JE, Butler G. BMC
Genomics 2006
Basidiomycota
Eurotiomycetes
Long Life
Short Life
SpheruleEndospores
Granuloma
Doctorfungus.comM. McGinnis
Coccidioides: Evolution of apathogen
Gene Family Evolutionin the Onygenales
ML phylogeny from 1148concatenated genes
46890 unambiguous AA sitesafter removing gaps.
Onygenales Familyexpansions
2 1
0 1
3 3
4 2
3 2
3 2
7 13
7 14
4 13
2 2
Peptidase M35
Keritinase
Keratinases in Onygenales
• Onygenales are Keratinophilic
• Domains: Peptidase S8, Subtilisin domains
• Large expansion of putative keratinases inOnygenales
Subtilisin_N
SignalP
Keratinase expansionin Onygenales
13/14 copies inCoccidioides
1 in Histoplasma
Expansion of 7
Metalloproteinase expansion
MEP
4
MEP
5
MEP
6
MEP
3
MEP
7
MEP
2
MEP
8
MEP1 is a previously described Virulencefactor (Hung et al. 2005)
Family contractions inOnygenales
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
Tan
nase
Cut
inas
e
Cel
lula
se
Cel
lula
seBi
ndin
gD
omai
n
Carbohydratemetabolism
• Domains absent or contracted inOnygenales fungi
• Tannase, Cutinase
• Pectin Lyase, Cellulase, Cellulase BindingDomain, Pectinesterase
• Alpha-L-arabinofuranosidase
• Glycosyl hydrolase
• HET domain
Summary
• Onygenales fungi have lost many domainsrelating to saprophytic growth on plantmatter
• Few expansions, but at least one family isrelated to a known virulence factor
• MEP genes are good Cocci specificexpansion
Basidiomycota changes
U.maydisC.cinereusP.chrysosporiumC.neoformans
P450 CYP64P450 enzymes involved in synthesis and cleavage ofchemical bonds. Drug metabolism in animals.
CYP64: Step in Aspergillus spp aflatoxin pathwayP. chrysosporium implicated in lignin and hydrocarbondegradation.
CYP64 was fromindependentduplication
C. cinereus expansion P. chrysosporium expansion
Tom VolkMario Cervini
Local duplications createdCYP64 expansion
Interpretation ofCYP64 expansion
Million yearsago
Hydrophobin Family
• Self assembling proteins involved in fungalcell wall
• Part of what makes a mushroom
• 8 Cysteine residues critical to function
• Help spores stay airborne resisting water
P.chr C.cin C.neo U.may
21 33 0 2
Local Duplications
C. cinereus
P. chrysosporium
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?
James et al. Nature 2006 Bruns TD. Nature 2006
Chytrid family changes• Expansions
•More Polysaccharide deacyetalase (2x) and Chitinbinding domains than most fungi
• 12 Chitin synthases, but R.oryzae has 23+, Mostother fungi have 1-5.
• Bd Contractions or small families in fungal ancestor
•No Glucan synthase (FKS1) homolog.
• Few Sugar transporters and Major FacilitorSuperfamily. No Acetate transporter.
•Of 9 P450 genes, 2 pairs are adjacent.
Discussion• Gene content differences not just
orthologous genes need to be consideredwhen describing species divergence.
• Losses may be more informative in someclades.
• Family size change can be a useful startingpoint for comparing species.
• Models that incorporate phylogeneticcontext are critical.
Acknowledgments
Miller Institutefor Basic Research in Science
Indiana UniversityMatthew Hahn
UC BerkeleyThomas Sharpton
John Taylor
Duke UniversityFred Dietrich
Sequencing CentersFGI, Broad Institute
DOE - JGITIGR
Stanford GTCBaylor College of
Medicine