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Comparative Genomics

Protein Homology Analysis

Three types of homology relationships are provided.

Protein trees

Protein trees are calculated using the longest peptide of all the Ensembl protein coding genes. Proteins are clustered based on Best-Reciprocal Hits and Blast Score Ratios. Each cluster of protein is aligned using Muscle. NJTREE is used to get a gene tree from each multiple alignment. The gene tree is reconciliated with the species tree to call duplication events.

Homologues

Homologues (orthologues and paralogues) are deduced from the protein trees. These are built using the longest transcript of each gene only. A detailed description of the method is provided here.

Families

Families are groups of related genes. The full set of Ensembl proteins is extended using all the metazoan proteins from SwissProt and SPTrEMBL.

BlastZ-net Analysis

BlastZ-net (Schwartz S et al., Genome Res.;13(1):103-7, Kent WJ et al., Proc Natl Acad Sci U S A., 2003;100(20):11484-9) alignments are provided for closely related pairs of species. The alignments are the results of post-processing the raw BlastZ results. In the first step, original blocks are chained according to their location in both genomes. The netting process chooses for the reference species the best sub-chain in each region. The reference species in the BlastZ-net alignments is defined in this table:

Homo sapiens H.sap
Pan troglodytes YES (on H.sap) P.tro
Macaca mulatta YES (on H.sap) - M.mul
Pongo pygmaeus YES (on H.sap) - - P.pyg
Mus musculus YES (on H.sap) - - - M.mus
Rattus norvegicus YES (on R.nor) - - - YES (on M.mus) R.nor
Cavia porcellus YES (on H.sap) - - - - - C.por
Oryctolagus cuniculus YES (on H.sap) - - - - - - O.cun
Felis catus YES (on H.sap) - - - - - - - F.cat
Canis familiaris YES (on H.sap) - - - YES (on M.mus) - - - - C.fam
Equus caballus YES (on H.sap) - - - - - - - - - E.cab
Bos taurus YES (on H.sap) - - - - - - - - - - B.tau
Dasypus novemcinctus YES (on H.sap) - - - - - - - - - - - D.nov
Echinops telfairi YES (on H.sap) - - - - - - - - - - - - E.tel
Loxodonta africana YES (on H.sap) - - - - - - - - - - - - - L.afr
Sorex araneus YES (on H.sap) - - - - - - - - - - - - - - S.ara
Microcebus murinus YES (on H.sap) - - - - - - - - - - - - - - - M.mur
Ochotona princeps YES (on H.sap) - - - - - - - - - - - - - - - - M.mur
Otolemur garnettii YES (on H.sap) - - - - - - - - - - - - - - - - - O.gar
Spermophilus tridecemlineatus YES (on H.sap) - - - - - - - - - - - - - - - - - - S.tri
Myotis lucifugus YES (on H.sap) - - - - - - - - - - - - - - - - - - - M.luc
Erinaceus europaeus YES (on H.sap) - - - - - - - - - - - - - - - - - - - - E.eur
Tupaia belangeri YES (on H.sap) - - - - - - - - - - - - - - - - - - - - - E.eur
Monodelphis domestica YES (on H.sap) - - - - - - - - - - - - - - - - - - - - - - M.dom
Ornithorhynchus anatinus YES (on H.sap) - - - YES (on M.mus) - - - - - - - - - - - - - - - - - - - O.ana
Gallus gallus YES (on H.sap) - - - - - - - - - - - - - - - - - - - - - - - - G.gal
Gasterosteus aculeatus - - - - - - - - - - - - - - - - - - - - - - - - - - G.acu
Oryzias latipes - - - - - - - - - - - - - - - - - - - - - - - - - - YES (on O.lat) O.lap
Ciona intestinalis - - - - - - - - - - - - - - - - - - - - - - - - - - - - C.int
Ciona savignyi - - - - - - - - - - - - - - - - - - - - - - - - - - - - YES (on C.int) C.sav
H.sap P.tro M.mul P.pyg M.mus R.nor C.por O.cun F.cat C.fam E.cab B.tau D.nov E.tel L.afr S.ara M.mur M.mur O.gar S.tri M.luc E.eur E.eur M.dom O.ana G.gal G.acu O.lap C.int C.sav

Translated Blat Analysis

Translated blat (Kent W, Genome Res., 2002;12(4):656-64) is used to look for homologous regions between more distantly related pairs of species. We expect to find homologies mainly in coding regions.

Homo sapiens H.sap
Mus musculus - M.mus
Rattus norvegicus - - R.nor
Gallus gallus YES YES - G.gal
Xenopus tropicalis YES YES - YES X.tro
Danio rerio YES YES YES YES YES D.rer
Takifugu rubripes YES YES - - - YES T.rub
Tetraodon nigroviridis YES YES YES - YES YES - T.nig
Gasterosteus aculeatus YES - - - - YES - - G.acu
Oryzias latipes YES - - - - YES - - - O.lap
Ciona intestinalis YES - - YES - YES - - - - C.int
Ciona savignyi YES - - YES - YES - - - - - C.sav
H.sap M.mus R.nor G.gal X.tro D.rer T.rub T.nig G.acu O.lap C.int C.sav

PECAN Analysis

Pecan is used to provide global multiple genomic alignments. First, Mercator is used to build a synteny map between the genomes and then Pecan builds alignments in these syntenic regions.

Pecan is a global multiple sequence alignment program that makes practical the probabilistic consistency methodology for significant numbers of sequences of practically arbitrary length. As input it takes a set of sequences and a phylogenetic tree. The parameters and heuristics it employs are highly user configurable, it is written entirely in Java and also requires the installation of Exonerate. Read more about Pecan.

Additionally we use Gerp (Cooper GM et al., Genome Res., 2005; 15:901-913) to calculate conservation scores and call constrained elements on the 10 way multiple alignments. Conservation scores are estimated on a column-by-column basis. Constrained elements are stretches of the multiple alignment where the sequences are highly conserved according to the previous score.

12 amniota vertebrates Pecan

Canis familiaris
Bos taurus
Mus musculus
Rattus norvegicus
Equus caballus
Homo sapiens
Pan troglodytes
Gallus gallus
Pongo pygmaeus
Monodelphis domestica
Ornithorhynchus anatinus
Macaca mulatta

EPO Analysis

The 23-way eutherian mammal alignments were generated using the new EPO (Enredo Pecan Ortheus) pipeline. Enredo produces colinear segments from extant genomes handling both rearrangements, deletions and duplications. Pecan, as described above, is used to align these segments. Finally, Ortheus is used to create genome-wide ancestoral sequence reconstructions. Manuscripts concerning these three components of the EPO pipeline are in preparation.

23 eutherian mammals EPO

Pan troglodytes
Mus musculus
Homo sapiens
Canis familiaris
Rattus norvegicus
Bos taurus
Macaca mulatta
Pongo pygmaeus
Equus caballus
Loxondonta africana
Dasypus novemcinctus
Echinops telfairi
Oryctolagus cuniculus
Cavia porcelus
Erinaceus europaeus
Sorex araneus
Myotis lucifugus
Tupaia belangeri
Spermophilus tridecemlineatus
Otolemur garnetii
Ochotona princeps
Microcebus murinus
Felis catus

The 4-way catarrhini-specific alignments were also generated using the new EPO (Enredo Pecan Ortheus) pipeline.

4 catarrhini-specific EPO

Homo sapiens
Pan troglodytes
Pongo pygmaeus
Macaca mulatta

Synteny Analysis

We calculate syntenic regions using blastz-net alignments. We look for stretches where the alignment blocks are in synteny. The search is run in two phases. In the first one, syntenic alignments that are closer than 200 kbp are grouped. In the second phase, the groups that are in synteny are linked provided that no more than 2 non-syntenic groups are found between them and they are less than 3Mbp apart.

Homo sapiens H.sap
Pan troglodytes YES P.tro
Macaca mulatta YES - M.mul
Pongo pygmaeus YES - - P.pyg
Mus musculus YES - - - M.mus
Rattus norvegicus YES - - - YES R.nor
Canis familiaris YES - - - YES - C.fam
Equus caballus YES - - - - - - E.cab
Bos taurus YES - - - - - - - B.tau
Monodelphis domestica YES - - - - - - - - M.dom
Gallus gallus YES - - - - - - - - - G.gal
H.sap P.tro M.mul P.pyg M.mus R.nor C.fam E.cab B.tau M.dom G.gal

 

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GermOnline based on Ensembl release 50 - Jul 2008
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