Unexpected Diversity in the Innate Immune System of

Unexpected Diversity in the Innate Immune System of

Unexpected Diversity in the Innate Immune System of the Purple Sea Urchin L. Courtney Smith Department of Biological Sciences George Washington University Washington DC 202-994-9211 Strongylocentrotus purpuratus Animal Phylogeny and the Evolution of Immunity Protostomes Arthropods Molluscs Annelids Deuterostomes Chordates Vertebrates Mammals Birds Reptiles Amphibians Fish Sharks & Rays Agnathans Lampreys Hagfish Protochordates Ascidians Echinoderms Sea Urchins Sea Urchin Genome Annotation Incomplete Complement System Missing Classical and Terminal pathways Duplication of Alternative pathway Large gene families Toll-like receptors, 222 gene models (humans have ~11) expressed in coelomocytes (immune cells) NOD-like receptors, 203 gene models (humans have ~20) expressed in gut Scavenger receptors, 218 gene models expressed in coelomocytes C-type lectins, 408 gene models (humans have ~100) encoding 108 small lectins, 300 mosaic proteins m e t s y S e n u m m I e t a n n I e s r e Highly Div

(Cohen & Smith, unpublished) Hibino et al., Dev Biol 300:349, 2006 TSUGSC, Science 314:941, 2006 Rast et al., Science 314:952, 2006 Gene Expression in Sea Urchin Immune Cells Responding to LPS Of 1025 randomly chosen ESTs, 72% matched to two unknown sequences. 185/333 All others EST333 (Smith et al., 1996) DD185 (Rast, Pancer & Davidson, 1999) Signal transduction 185/333 All others Unknown Protein metabolism Protease activity Nuclear activities Molecular Defense transport Metabolism Nair et al., Physiol Genomics 2005. Bad sequence Cytoskeletal elements Alignment of 185/333 cDNAs 300 nt Gaps define blocks of sequence called elements. Alternative splicing? Terwilliger et al., Physiol Genomics 2006 185/333 Gene Structure 407bp Leader Elements 1 - 25 E2 < 2 kb Quantitative PCR estimates 80 - 120 alleles per genome Terwilliger et al., Physiol Genomics 2006 B C D E F 0 Exon 2 elements 1 3 B A

b 6* 1 S A b 5* 1 S B b 2 1 S C b 3d 5 S B b 3b 5 B B b 6* 2 S D b 7* 1 S C b 3 2 S C b 3* 1

S C b 4* 1 S D b 1 28 B C b 5* 3 C C 6 1 C C a Source # A Gene Element Patterns Pattern Group Exon 1 L Int. 1 2 3 4 5 6 7 9 12 16 21 8 10 11 13 14 15 17 18 19 20 22 23 24 25 c

3f 6 C E a 3c 1 C C a 2 14 B E a 7* 1 C E b 8* 1 C E b 9* 1 C E c 1* 1 C B b 2* 4 C B 2* 1 C E b

a 1f 12 B E b 1c 1 S C b 1e 1 S D b 300 bp Intron elements A B C D E 1 2 3 4 5 6 7 8 9 100 bp Buckley & Smith, in prep 185/333 Sequence Diversity Element diversity is a result of SNPs and indels Sequences of identical genes are rarely identified within an individual sea urchin Identical genes are never shared among sea urchins. Some element sequences are shared among dissimilar genes Element Scrambling L3 3 3 11

5 3 7 2 Intron Elements 13 1 1 1 14 19 1 2 1 2 2 1 12 6 4 17 1 1 1 3 1 2 2 1 1 11 6 6 7 8 20 3 6 1 1 2 1 5 5

6 4 6 18 39 9 1 17 17 2 13 6 6 3 4 3 6 7 2 2 3 3 2 30 3 8 4 5 5 1 3 2 1 7 3 5 13 2 14 5 3 6 4 1 4 2 11 29

8 6 19 10 7 7 4 8 2 1 14 12 12 12 7 3 1 7 15 1 1 18 25 41 1 25 5 10 35 6 7 21 5 19 3 22 4 9 1 16 23 10 8 2 3 61 1 34 17 14 18 6

2 11 5 9 10 16 3 9 9 1 57 67 19 Exon 2 Elements 1 4 3 5 2 10 13 9 2 17 4 1 2 1 10 7 2 13 12 9 4 2 1 10 1 4 3 19 11 2 1 21 2 2 37 8

20 11 46 38 unique genes from animal 10 9 9 5 1 5 Buckley & Smith, in prep 20 28 Conclusions Complex immune system Large gene families Unknown mechanisms for diversification Do all metazoa have mechanisms for immune diversification? Future Problems 185/333 locus structure 185/333 protein function Acknowledgments George Washington University David Terwilliger Katherine Buckley Virginia Brockton Rebecca Easley Young-Ok Kim Heather Del Valle Lindsay Edwards Macquarie University David Raftos Sham Nair Nolwen Dheilly Duke University Tom Kepler Supriya Munshaw Dickinson College John Henson Medical Univ. of S. Carolina Paul Gross Sea urchin immunology is supported by the National Science Foundation

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