Diagrammatic representation of the structures and evolutionary origins of the granulin in multicelluar organisms. Evolutionary distances in millions of years derived from Hedges 2002 . The estimated rounds of vertebrate genome duplication events are indicated (1R, 2R, 3R). The various progranulin structures were derived from various databases as outlined below. Land plant – (Arabidopsis thaliana) – Papain-like thiol protease bearing a carboxyl-terminal granulin domain (AAK71314); Slime mold – (Dictyostelium discoideum) – 1 copy progranulin from a single EST (AU267401) Trematode worm (Schistosoma japonicum) – 9 copy progranulin built from a combination of four ESTs (AY810079, BU790215, BU799560, BU771494); Nematode worm – (Caenorhabditis elegans) – 3 copy progranulin from single EST (NM_060580) – overall architecture confirmed by genome sequence (Z81595); Annelid worm (earthworm – Lumbricus rubellus) – 1 copy progranulin from a single EST (CO046860); Primitive chordate – (Sea squirt, Ciona intestinalis) – 7 copy progranulin predicted from draft genomic sequence (AABS01000126) and overall architecture confirmed by ESTs. Domains 2 to 7 nearly identical (BW368775, BW311239). Amphibian – (Frog, Xenopus laevis) co-orthologues progranulins A and B consisting of one-half domain followed by 12 full domains and one-half domain followed by nine full domains respectively . These are structurally closely related and are a result of a recent tetraploidization event 30 mya . Avian (chicken – Gallus gallus) – 4 copy progranulin built from three ESTs (BM440305, BU297352 and BX265765) – overall architecture confirmed by genome sequence (LOC426606); Human (Homo sapiens) – Progranulin composed of one half domain followed by 7 domains (UniProt entry: P28799); Teleost – Takifugu rubripes – 2, 3 and 11 copy progranulins predicted from draft genome sequences (M000077, S002118, S0001020) with overall structures confirmed by ESTs (CA846088, CA332411, AL842916, CA588603). Teleost – Danio rerio: from this study: co-orthologue progranulins A and B composed of 10 (NM_001001949) and 9 (AY289606) respectively; two smaller progranulins consisting of 1 and one half granulin repeats (AF273479, AF273480).