title: Schistosome dystrophin and dystrobrevin proteins contain large insertions.
abstract: Dystrophin and dystrobrevin are distantly related proteins that form a heterodimeric membrane-bound complex in all metazoa so far studied. The signature feature of the dystrophin/dystrobrevin/dystrotelin superfamily is a highly conserved cluster of domains whose integrity and size are maintained in all known members- more than 60 sequences so far reported. We were therefore surprised to find that the analogous regions of the Schistosoma mansoni proteins bear multiple large insertions amounting to 100% (dystrophin) and 35% (dystrobrevin) of their expected size. We isolated orthologous sequences from Schistosoma haematobium and Schistosoma bovis, and found that the insertions have a 10-fold higher rate of change (Ka/Ks value) than their respective host sequences, suggesting a much lower degree of functional constraint. A survey of known S. mansoni protein sequences shows that only two other proteins (both acetylcholine receptors) share these properties. We discuss the implications of the positions and sizes of these insertions for the structure and function of the dystrophins and dystrobrevins.
authors.affiliation: Division of Genetics & Molecular Medicine, Department of Medical & Molecular Genetics, King's College London, Guy's Hospital, London SE1 9RT, UK.
authors.forename: Sipin
authors.initials: S
authors.lastname: Tan
authors.forename: David A
authors.initials: DA
authors.lastname: Johnston
authors.forename: Roland G
authors.initials: RG
authors.lastname: Roberts
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016189:Dystrophin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D049029:Dystrophin-Associated Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D010802:Phylogeny; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011950:Receptors, Cholinergic / Q000378:metabolism; D012550:Schistosoma mansoni / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D016189:Dystrophin; D049029:Dystrophin-Associated Proteins; D011950:Receptors, Cholinergic; C098885:dystrobrevin