Comparative genomics of fung: studying adaptation through gene family evolution
of fungi: studying
gene family evolution
University of California, Berkeley
Gene family evolution
• How do fungi adapt to a niche? How do
they acquire new functions and new genes?
• Horizontal Transfer
• Duplication and innovation
• Are genome-wide patterns of duplication
or loss useful to understand adaptation?
Gene family sizes follow
power law distribution
single copy genes
CDC48 (cell cycle ATPase)
Models of gene family
• Need a Null model for comparison of gene
• Birth-Death model for gene family size
• CAFE: Computational Analysis of Family
• Compare observed to expected patterns
of family size
Hahn et al, Genome Res 2005
Demuth et al, PLoS One 2006
Case study: mammals
Demuth JP, De Bie T, Stajich JE, Cristiani N, Hahn MW. PLoS One 2006
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
• Build gene trees to validate and study mode and
tempo of duplication.
• Protein Domain distribution
• Pfam domain counts
10 1 2
14 18 2
7 1 1
6 1 12
6 1 8
3 1 1
Family 1 P < 0.001 Branch A
Family 2 P < 0.001 Branch B
Family 3 P=0.02 C,E
Family 4 P=0.03 Branch D
Phylogeny of sequenced fungi
Fitzpatrick DA, Logue ME,
Stajich JE, Butler G. BMC
Coccidioides: Evolution of a
D octorfungus. com
Gene Family Evolution
in the Onygenales
ML phylogeny from 1148
46890 unambiguous AA sites
after removing gaps.
• Domains absent or contracted in
• Tannase, Cutinase
• Pectin Lyase, Cellulase, Cellulase Binding
• Glycosyl hydrolase
• HET domain
• Onygenales fungi have lost many domains
relating to saprophytic growth on plant
• Few expansions, but at least one family is
related to a known virulence factor
• MEP genes are good Cocci speciﬁc
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
CYP64 was from
C. cinereus expansion P. chrysosporium expansion
Mario Cervini Tom Volk
P.chr C.cin C.neo U.may
21 33 0 2
• Self assembling proteins involved in fungal
• Part of what makes a mushroom
• 8 Cysteine residues critical to function
• Help spores stay airborne resisting water
•Local duplications are a major mode of family
expansion in two Homobasidiomycetes
•Independent expansion of families
•High gene turnover in some families?
Bruns TD. Nature 2006
James et al. Nature 2006
Chytrid family changes
• 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.
• Gene content differences not just
orthologous genes need to be considered
when describing species divergence.
• Losses may be more informative in some
• Family size change can be a useful starting
point for comparing species.
• Models that incorporate phylogenetic
context are critical.
Matthew Hahn Miller Institute
for Basic Research in Science
FGI, Broad Institute
DOE - JGI
Baylor College of