FOG: HighResolution Fungal Orthologous Groups

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FOG High-Resolution Fungal Orthologous Groups

• René van der Heijden

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What is this presentation about?

• What is orthology?
• Why do we study gene-ancestry/gene-trees
  (phylogenies)?
• Why high-resolution orthology?
• Automated high-resolution orthology detection
• The FOG database and some applications

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Orthology

• This gene in that other species
• We dont have chicken genes !
• They mean the corresponding gene ?
• Why that particular gene ?
• Sure this actually is the gene ?
• Sure that all n orthologs are correct ?

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Orthologous genes
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Duplications, Speciations, and Orthology

• Two genes in two species are orthologous if
• they derive from one gene
• in their last common ancestor

gene duplication by cell division
Orthologous genes are likely to have the same
function
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Detecting orthologous genes

• Usual methods based on blast hit qualitye.g.
  bi-directional best hit (BBH)

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KOG clusters

• Based on triangle of BBH between genes of three
  species
• InParalogs are added
• Triangles are extended by other genes and other
  species

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KOG statistics
Low Resolution There must be functional
specialization within these clusters!
These large KOG clusters must have multiple
representatives per species
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High-res versus Low-res

• Many,
• Complete, and
• Closely related
• genomes

Challenge Automatic Orthology assignment
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Gene Families

• Use PSI-blast to recognize (distant) homologs
• Split gene set into families of homologous genes

Challenge Promiscuous domains
Multi domain genes occur very often in
Eukaryotic genomes
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Gene Families

• Promiscuous domains cause genes to be only
  partially homologous
• Gene A-B is partially homolgous to gene A-C, as
  is gene B-C
• Merging everything with homologous parts
  generates far too large gene families
• Not possible to obtain proper multiple alignments
• More advanced technique for separating
  multi-domain genes into gene families

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Generating Gene Families

• More advanced technique for the merging of genes
  into gene families is not functional yet
• Fall back on known gene families using KOG
• Low resolution orthology assignments for
  Eukaryotes
• Some inclusive families with many genes per
  species
• Some statistics
• 15 Fungal species with 104.440 genes in total
• Divided into 11.020 KOG clusters (gene families)
• Involving 70.867 genes ( 68)

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Uncertainty in trees

• Evolutionary noise
• Differing rates of evolution
• Convergent evolution (low complexity, coiled
  coils)
• Promiscuous domains (recombination, fusion,
  fission)
• Use of heuristic methods
• Multiple alignment
• Tree making

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Reading Gene-Trees
Although genes spec1,1 and spec2,1 are closer
relatives, their distance is larger than that
between spec1,1 and spec3,1
The tree suggests at least 2 gene losses
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Analyze trees but dont trust them fully
If this is correct . this cant be

• Rigid analysis suggests many duplications and
  losses
• Presume scp branch is wrongly placed!

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Analyze trees but dont trust them fully

• And if we accept wrong placement of branches

Three orthologous groups suggesting 15 gene
losses
Considering one wrongly placed gene leaves only 2
gene losses
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Automatic Orthology assignment

• LOFT Levels of Orthology From Trees

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Result

• Collection of genes is split into KOG families
• KOG families are aligned and phylogenetic trees
  are derived
• Phylogenetic trees are analyzed using LOFT
  resulting in high-resolution orthology

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Result
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Can LOFT be trusted?
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It seems okay!
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Applications

• We now have FOG a complete set of high
  resolution orthology assignments for fungi
• We know which orthologous genes are present and
  absent in which species
• Phyletic distribution

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Complex I
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Complex I
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Complex I
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Phyletic distribution of mitochondrial
orthologous groups
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Phylogenetic Tree for Mitochondrial Carrier
Proteins
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Orthologous group 24 is an uncharacterized
mitochondrial carrier
In yeast this is known as YMC1, unknown function
It is present in all fungi, except in Ashbya
gossypii
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YMC1 predicted glycine/serine antiporter

• There are three S.cerevisiae genes with the same
  phyletic distribution
• subunit glycine decarboxylase
• other subunit glycine decarboxylase
• gene with unknown function