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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 l.jpg

The evolution of the immune system in chicken and higher vertebrates

@ Organon, Oss

2005-09-20

Tim Hulsen


Biorange project sp3 2 2 l.jpg

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


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M. Groenen: chicken sequencing


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Kaiser: chicken immune system


Introduction l.jpg

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 l.jpg

Overview

  • Find IS-related proteins

  • Determine orthologies

  • Pfam annotation

  • Panther annotation

  • Zooming in


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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


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Step 1: Find IS-related proteins


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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


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Step 1: Find IS-related proteins

  • Result:

    • 1381 proteins through IRIS

    • 1515 proteins through GO

    • 1929 proteins total


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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)


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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


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Step 2: Determine orthologies


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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


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Step 2: Determine orthologies


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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 (2814mappings)


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Step 3: Pfam annotation


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Step 3: Pfam annotation


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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)


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Step 4: Panther annotation


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Step 4: Panther annotation


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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


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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)


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Credits

  • NV Organon:

    • Peter Groenen

    • Wilco Fleuren

  • Wageningen UR:

    • Martien Groenen

    • Hindrik Kerstens

  • Compton (UK):

    • Pete Kaiser


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