Download Comparative Genomics

Comparative Genomics
How does Ensembl compare species?
• Proteins: Homologs & Families
• Genomes: Sequence Alignments
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Ensembl Homologues
56 species in v65
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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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Viewing Trees in Ensembl
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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
dog?
2. If so, in what location (chromosome and base
pairs) is the dog homologue found?
3. Can you find the cDNA alignment between the
human and dog 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 …
34
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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Let’s look at alignments!
Go to the Location tab (Region in detail view) for the
human RHO gene
Turn on the following alignments:
• Human-Alpaca
• Human-Zebrafish
• Primates
1) Compare the zebrafish and alpaca alignments to the
human genome. Which has more regions of alignment?
2) What does the 6 primates alignment tell you?
Conservation in Alignments
Now turn on the following tracks:
• Conservation score for 35 eutherian mammals
• Constrained elements for 35 eutherian mammals
1) Are the RHO 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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Synteny exercise
Click on Synteny in the location tab.
1. How many chromosomes in dog have
syntenic regions to human chromosome 3?
2. Click „15 downstream genes‟. Are there dog
homologues to the human gene list?
Advanced views
Explore the Alignments (image), Alignments
(text) and Multi-species view in the location
tab.
1. View alignments between human and dog in
these three views. Which view do you prefer?
Acknowledgements
•
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Javier Herrero
Kathryn Beal
Stephen Fitzgerald
Leo Gordon
Matthieu Muffato
Miguel Pignatelli
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