1. Phylogenetic genome analysis, phylogenomics
Bas E. Dutilh

2. What we can see

3. Family tree → species tree
Offspring looks like its parents
Darwin: species evolve like families

4. Species tree

5. Tree of life
Archaea
Bacteria
Eukaryota

6. Phylogeny Term coined by Ernst Haeckel (1866) Phylon (Greek: fulon)
Tribe
Race
Genus (Latin)
Birth
Origin

7. Phenotype ↔ genotype Infinite # features Subjective choice
Value can depend on observation (etc.)
Gene/genome is finite
Objective choice
A sequence is absolute

8. Convergence
Contrary to phenotype or structure, sequences do not converge
Highly dimensional: every residue is a dimension

9. Phylogenetic markers Available/easy to sequence Present in all species
Cytochrome C
Present in all species
Constant function
Slowly evolving
SSU rRNA
Fitch, Science1967
Woese et al, PNAS 1977

10. SSU rRNA Phylogeny of SSU rRNA discovered the three domains
Representative for the evolutionary history of species
Archaea
Bacteria
Eukaryota

11. Phylogenetic assumptions
Sequences are homologous – have a common ancestor
Sequences diverge in a binary fashion
Each position evolves independently

12. Phylogenetics Neighbor joining Maximum parsimony Maximum likelihood
Which tree assumes the fewest mutations?
Maximum likelihood
For a given model, which tree has the highest probability of generating observed alignment?

13. Bootstrapping Jackknifing
Randomly re-sample all columns in the alignment with replacement
Re-create trees
Count presence of each branch
Jackknifing
Delete fraction of columns
Re-create tree

14. Different genes tell different stories
Conflict between trees based on single genes
Unrecognized paralogy
Horizontal gene transfer
Mutation saturation, biases, divergent rates
spec B
spec A
- Paralogs
- Orthologs
ancestor
spec C

15. More data → more consistent trees
Combine information from more genes to average out these anomalies
Complete genomes contain the maximum phylogenetic information
Dutilh et al, Bioinformatics 2007

16. Chimeric genomes
Is a tree the right representation of the evolutionary history of a genome?
Endosymbiosis (mitochondrion, chloroplast)
Horizontal gene transfer (many examples, often adaptations to environment)
Darwin, 1859
Doolittle, Science 1999

17. Densitree “Fuzzy” trees Draw the tree lots of times
Bootstrap
Different genes
Use transparency to make fuzziness

18. Splitstree Tries to accommodate non-bifurcating nodes
Some positions evolve independently
Parallel edges are related

19. Genomic properties Word frequency Sequence (nt/aa) Gene content
Gene order

20. Dutilh et al, Bioinformatics 2007
Fungi
Yeasts, filamentous
and dimorphic fungi
Fungi are the eukaryotic clade with largest number of completely sequenced genomes
S. cerevisiae is a well studied model organism
Much consensus about phylogeny
Dutilh et al, Bioinformatics 2007

21. Consensus phylogeny (literature)
19 target nodes
Dutilh et al, Bioinformatics 2007

22. 13 trees
14 trees
15 trees
12 trees

23. Gene content methods Presence/absence matrix (0/1)
Similarity: number of shared orthologous groups
Genomes that share few OGs are distantly related
Genomes that share many OGs are closely related
OG1 OG2 OG3 OG4 …
sp …
sp …
sp …
… … … … …
but…
Snel et al, Nat Genet 1999
Tekaia et al, Genome Res 1999

24. Genome size correction
Large genomes have more genes, so they also share more genes
Divide number of shared genes by
Average genome size
Smallest of two genomes
Weighted average genome size
P. chrysosporium
# shared genes
genome size
Korbel et al, TiG 2002

25. Saitou et al, Mol Biol Evol 1987
Gene content methods
Similarity: corrected number of shared genes
Distance: (1 – similarity)
Neighbour joining
( )
# shared OGs (spA, spB)
weighted average size (spA, spB) d
0.8 0
dist (spA, spB) = 1 –
\s sp1 sp2 sp3 sp4 …
sp1 \ …
sp \ …
sp \ …
sp \1 …
… … … … …
Saitou et al, Mol Biol Evol 1987

26. Superalignment methods
Multiple alignment
Concatenate alignments (1:1:1)
A missing gene in a certain species (row) can be seen as a gap in the alignment

27. Select positions Percentage gaps Percentage conservation GBlocks
Slow-fast
Castresana, Mol Biol Evol 2000
Brinkmann et al, Mol Biol Evol 1999

28. Gene content vs. sequence
Gene content supertrees are different than sequence based supertrees
Dutilh et al, Bioinformatics 2007

29. “Hot” origin of life?
Protein sequence
Gene content

30. Other evidence Membrane composition Gene structure
Plötz et al, J Biol Chem 2000
Gene structure
Gribaldo et al, J Bact 1999

31. Light from different angles
Sequence
Phylogenetic trees (marker genes)
Phylogenomic trees
Gene content
Gene content trees
Signature genes
Phenotype
Morphology
Metabolism / chemistry

32. Highly similar strains
Almost identical gene content
Low recombination rate
Whole genome alignment
Mauve
Nucmer
Extract positions that are not completely conserved from the genome alignment
SNPs
Small indels
Abundance
Recombination rate