Comparative Genomics
How does Ensembl compare species?
•  Proteins: Homologs & Families
•  Genomes: Sequence Alignments
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Ensembl Homologues
e70: 73 genomes (61 fully supported, 12 on Pre!)
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Types of Homologues
•  Orthologues : a homologue where the
ancestor node is a speciation event
•  Paralogues : a homologue where the ancestor
node is a duplication event
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Orthologues are between species,
paralogues are within a species
EnsemblCompara GeneTrees: Analysis of complete, duplication aware phylogenetic trees in
vertebrates. Vilella AJ, Severin J, Ureta-Vidal A, Durbin R, Heng L, Birney E. Genome Res. 2008 Nov
24.
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The Gene Tree for INS
(insulin precursor)
A blue square
is a
speciation
event
(Orthologues)
A red square
is a
duplication
event
(Paralogues)
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Gene Trees
Amino Acid
alignments
Tree with
ancestor
nodes
Expanded nodes:
Aligned
Amino Acid
Gap
Collapsed (triangle) nodes:
>66%
Consensus
33-66%
Consensus
Orthologue Types
What is ‘1 to 1’?
What is ‘1 to many’?
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Quick exercise
MYO6 is a myosin that has been shown (when
mutated) to be associated with deafness.
1.  Does human MYO6 have a homologue in
mouse?
2.  If so, in what location (chromosome and base
pairs) is the mouse homologue found?
3.  Can you find the cDNA alignment between the
human and mouse homologues?
www.ensemblgenomes.org
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Pan-taxonomic compara
Anolis carolinensis
Ciona savignyi
Danio rerio
Equus caballus
Gallus gallus
Homo sapiens
Macaca mulatta
Monodelphis domestica
Mus musculus
Ornithorhynchus anatinus
Pan troglodytes
Pongo pygmaeus
Xenopus tropicalis
Anopheles gambiae
Caenorhabditis elegans
Drosophila melanogaster
Dictyostelium discoideum
Plasmodium falciparum
Plasmodium vivax
Arabidopsis thaliana
Oryza sativa
Vitis vinifera
B_aphidicola_Tokyo_1998
B_burgdorferi_DSM_4680
B_subtilis
E_coli_K12
M_tuberculosis_H37Rv
N_meningitidis_A
P_horikoshii
S_aureus_N315
S_pneumoniae_TIGR4
S_pyogenes_SF370
W_pipientis_wMel
Aspergillus nidulans
Neurospora crassa
Saccharomyces cerevisiae
Schizosaccharomyces pombe
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Protein Families
•  How: Cluster proteins for every
isoform
in every species + UniProt
proteins.
•  BLASTP comparison of:
–  all Ensembl ENSP…
–  all metazoan (animal) proteins in UniProt
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How does Ensembl compare species?
•  Proteins: Homologs & Families
•  Genomes: Sequence Alignments
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Whole Genome Alignments
Pairwise (two species)
•  Nucleotide alignment: BLASTZ/LASTZ-net
closer species e.g. human – mouse
•  Amino acid alignment: Translated BLAT
more distant species, e.g. human – zebrafish
Multi-species (more than two species)
•  Nucleotide alignments: EPO/PECAN
selected sets (primates, fish, birds, mammals, vertebrates)
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Within an alignment …
36
mammals
are aligned
Human
genome
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Scoring the nucleotides
High score
goes to
conserved
nucleotides
atgccgt
acgcgat
acgtctt
GERP scoring of every nucleotide in the alignment
(Cooper GM et al., Genome Res., 2005; 15:901-913)
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High scoring blocks
High scoring
nucleotides
make up the
‘constrained
elements’
acgcgat
acgcgat
acgcgat
…
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Exercise
Go to the Location tab for the human Myo6
gene.
1)  Compare the mouse, cow, and human
genomes in this region.
2) Do all species in the 13 eutherian
mammal alignment have a gene in this
locus?
Conservation in Alignments
Now turn on the following tracks:
•  Conservation score for 36 eutherian
mammals
•  Constrained elements for 36 eutherian
mammals
Q) Are the Myo6 exons in regions of high
sequence conservation?
Non-Coding Regions
•  “Phylogenetic Footprinting” – conserved
noncoding regions can be functional
•  Regulatory regions discovered in this way
for genes:
Hoxb-1, Hoxb4, PAX6, SOX9
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Regulatory Features of the PDX1
gene
Region in Detail shows conservation of sequence in regions
involved in PDX1 transcriptional regulation
(1.6-2.8 kb upstream of the gene).
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Syntenic regions
Syntenic regions
Blastz/
Lastz
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Synteny
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Acknowledgements
•
•
•
•
•
•
Javier Herrero
Kathryn Beal
Stephen Fitzgerald
Leo Gordon
Matthieu Muffato
Miguel Pignatelli
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