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The evolution of the immune system in chicken and higher vertebrates. @ Organon, Oss 2005-09-20 Tim Hulsen. Biorange Project SP3.2.2. Chicken immunosystem project is part of WP1, “Translational Medicine through Comparative Genomics and Integration” Partners:

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the evolution of the immune system in chicken and higher vertebrates

The evolution of the immune system in chicken and higher vertebrates

@ Organon, Oss

2005-09-20

Tim Hulsen

biorange project sp3 2 2
Biorange Project SP3.2.2
  • Chicken immunosystem project is part of WP1, “Translational Medicine through Comparative Genomics and Integration”
  • Partners:
    • Animal Breeding and Genetics Group, Wageningen UR (Prof. dr. Martien Groenen)
    • Avian Cytokines Group, Institute for Animal Health, Compton (UK) (Prof. dr. Pete Kaiser)
  • Jack Leunissen (WUR) also part of WP1
introduction
Introduction
  • Goal: developing an insight in the recent evolution of the immune system
  • Usage of a more distant species: chicken (recently sequenced)
  • Support by experimental data
overview
Overview
  • Find IS-related proteins
  • Determine orthologies
  • Pfam annotation
  • Panther annotation
  • Zooming in
step 1 find is related proteins
Step 1: Find IS-related proteins
  • IRIS: “Immunogenetic Related

Information Source”

  • number of immune genes: 1562 (out of 21389 in LocusLink)
  • percentage of genome related to immunity: 7.30%
  • 1562 LocusLink proteins mapped to our Protein World set: 1381 proteins
step 1 find is related proteins9
Step 1: Find IS-related proteins
  • GO: Gene Ontology
  • collaborative effort to address the need for consistent descriptions of gene products in different databases
  • Checked human GO annotation for certain terms: “immunology”,”cytokine”,etc.
  • 1515 proteins in human Potein World set
step 1 find is related proteins10
Step 1: Find IS-related proteins
  • Result:
    • 1381 proteins through IRIS
    • 1515 proteins through GO
    • 1929 proteins total
step 2 determine orthologies
Step 2: Determine orthologies
  • Study evolution from chicken (Gg) to rat (Rn), mouse (Mm) and human (Hs):
    • Hs<->Mm
    • Hs<->Rn
    • Hs<->Gg
    • Mm<->Rn
    • Mm<->Gg
    • Rn<->Gg
  • Two methods: Best Bidirectional Hit (BBH) and PhyloGenetic Tree (PGT)
best bidirectional hit bbh
Best Bidirectional Hit (BBH)
  • Very easy and quick
  • Human protein (1)  SW  best hit in mouse/rat (2)
  • Mouse/rat protein (2)  SW  best hit in human (3)
  • If 3 equals 1, the human and mouse/rat protein are considered to be orthologs
phylogenetic tree pgt

PROTEOMES

SELECTION OF HOMOLOGS

LIST

ALIGNMENTS AND TREES

PHYLOME

PhyloGenetic Tree (PGT)

PROTEOME

Human

Human, mouse, rat, chicken

Hs, Mm, Rn, Gg

Z>20 RH>0.5*QL

~25,000 groups

Hs-Mm pairs

Hs-Rn pairs

Hs-Gg pairs

Mm-Rn pairs

Mm-Gg pairs

Rn-Gg pairs

TREE SCANNING

step 3 pfam annotation
Step 3: Pfam annotation
  • Pfam: “Protein families database of

alignments and HMMs”

  • collection of protein families and domains
  • Pfam contains multiple protein alignments and profile-HMMs of these families
  • 75% of protein sequences have at

least one match to Pfam

  • 1700 IS-related proteins mapped to 584 Pfam families (2814 mappings)
step 4 panther annotation
Step 4: Panther annotation
  • PANTHER: “Protein ANalysis

THrough Evolutionary Relationships”

  • designed to classify proteins (and their genes) in order to facilitate high-throughput analysis
  • proteins have been classified according to families and subfamilies, molecular functions, biological processes, pathways
  • contains over 6683 protein families, divided into 31,705 functionally distinct protein subfamilies
  • 1872 IS-related proteins mapped to 970 Panther families (4667 subfamilies, 14737 mappings)
step 5 zooming in
Step 5: Zooming in
  • Which families are ‘new’ in human?
  • Which orthologs have a different domain structure through evolution?
  • Which human proteins don’t have orthologs in the other species?
  • Any other interesting stuff
future directions
Future directions
  • Include paralogs in our analysis (makes possible checking which families only exist in mouse/rat/chicken)
  • Combine our findings with research at WUR: synteny between human and chicken
  • Take a look at ratio of non-synonymous to synonymous substitutions (dN/dS)
credits
Credits
  • NV Organon:
    • Peter Groenen
    • Wilco Fleuren
  • Wageningen UR:
    • Martien Groenen
    • Hindrik Kerstens
  • Compton (UK):
    • Pete Kaiser
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