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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. 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

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  1. The evolution of the immune system in chicken and higher vertebrates @ Organon, Oss 2005-09-20 Tim Hulsen

  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

  3. M. Groenen: chicken sequencing

  4. Kaiser: chicken immune system

  5. 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

  6. Overview • Find IS-related proteins • Determine orthologies • Pfam annotation • Panther annotation • Zooming in

  7. 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

  8. Step 1: Find IS-related proteins

  9. 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

  10. Step 1: Find IS-related proteins • Result: • 1381 proteins through IRIS • 1515 proteins through GO • 1929 proteins total

  11. 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)

  12. 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

  13. Step 2: Determine orthologies

  14. 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

  15. Step 2: Determine orthologies

  16. 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)

  17. Step 3: Pfam annotation

  18. Step 3: Pfam annotation

  19. 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)

  20. Step 4: Panther annotation

  21. Step 4: Panther annotation

  22. 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

  23. 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)

  24. Credits • NV Organon: • Peter Groenen • Wilco Fleuren • Wageningen UR: • Martien Groenen • Hindrik Kerstens • Compton (UK): • Pete Kaiser

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