Functional evolution of ADAMTS genes: evidence from analyses of phylogeny and gene organization.
BACKGROUND
The ADAMTS (A Disintegrin-like and Metalloprotease with Thrombospondin motifs) proteins are a family of metalloproteases with sequence similarity to the ADAM proteases, that contain the thrombospondin type 1 sequence repeat motifs (TSRs) common to extracellular matrix proteins. ADAMTS proteins have recently gained attention with the discovery of their role in a variety of diseases, including tissue and blood disorders, cancer, osteoarthritis, Alzheimer's and the genetic syndromes Weill-Marchesani syndrome (ADAMTS10), thrombotic thrombocytopenic purpura (ADAMTS13), and Ehlers-Danlos syndrome type VIIC (ADAMTS2) in humans and belted white-spotting mutation in mice (ADAMTS20).


RESULTS
Phylogenetic analysis and comparison of the exon/intron organization of vertebrate (Homo, Mus, Fugu), chordate (Ciona) and invertebrate (Drosophila and Caenorhabditis) ADAMTS homologs has elucidated the evolutionary relationships of this important gene family, which comprises 19 members in humans.


CONCLUSIONS
The evolutionary history of ADAMTS genes in vertebrate genomes has been marked by rampant gene duplication, including a retrotransposition that gave rise to a distinct ADAMTS subfamily (ADAMTS1, -4, -5, -8, -15) that may have distinct aggrecanase and angiogenesis functions.
Nicholson
Ainsley C
AC
Laboratory of Molecular Neuro-Oncology, Neurosurgery Department and Winship Cancer Institute, 1365-C Clifton Road, Room C5078, Emory University, Atlanta, GA 30322, USA. agn0@cdc.gov
Malik
Shehre-Banoo
SB
Logsdon
John M
JM
Van Meir
Erwin G
EG
D051722:ADAM Proteins / Q000737:chemistry* / Q000378:metabolism; D020816:Amino Acid Motifs; D000818:Animals; D017173:Caenorhabditis elegans; D002938:Ciona intestinalis; D003198:Computer Simulation; D004330:Drosophila; D019143:Evolution, Molecular; D020224:Expressed Sequence Tags; D020440:Gene Duplication; D016678:Genome; D006801:Humans; D007438:Introns; D008957:Models, Genetic; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D012984:Software
D051722:ADAM Proteins