Evolution of the Vertebrate Paralemmin Gene Family Ancient Origin of Gene Duplicates Suggests Distinct Functions 英文参考文献.docVIP

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Evolution of the Vertebrate Paralemmin Gene Family Ancient Origin of Gene Duplicates Suggests Distinct Functions 英文参考文献.doc

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Evolution of the Vertebrate Paralemmin Gene Family Ancient Origin of Gene Duplicates Suggests Distinct Functions 英文参考文献

EvolutionoftheVertebrateParalemminGeneFamily: AncientOriginofGeneDuplicatesSuggestsDistinct Functions GretaHultqvist1*¤,DanielOcampoDaza2,DanLarhammar2,ManfredW.Kilimann1 1Department of Neuroscience, Unit of Molecular Cell Biology, Uppsala University, Uppsala, Sweden, 2Department of Neuroscience, Unit of Pharmacology, Uppsala University,Uppsala,Sweden Abstract Paralemmin-1isaproteinimplicatedinplasmamembranedynamics,thedevelopmentoffilopodia,neuritesanddendritic spines,aswellastheinvasivenessandmetastaticpotentialofcancercells.However,littleisknownaboutitsmodeofaction, or about the biological functions of the other paralemmin isoforms: paralemmin-2, paralemmin-3 and palmdelphin. We describe here evolutionary analyses of the paralemmin gene family in a broad range of vertebrate species. Our results suggest that the four paralemmin isoform genes (PALM1, PALM2, PALM3 and PALMD) arose by quadruplication of an ancestralgeneinthetwoearlyvertebrategenomeduplications.Paralemmin-1andpalmdelphinwerefurtherduplicatedin theteleostfishspecificgenomeduplication.Weidentifiedauniquesequencemotifcommontoallparalemmins,consisting of11highlyconservedresiduesofwhichfourareinvariant.Asinglefull-lengthparalemminhomologwiththismotifwas identified in the genome of the sea lamprey Petromyzon marinus and an isolated putative paralemmin motif could be detectedinthegenomeofthelanceletBranchiostomafloridae.Thisallowsustoconcludethattheparalemmingenefamily arose early and has been maintained throughout vertebrate evolution, suggesting functional diversification and specific biological roles of the paralemmin isoforms. The paralemmin genes have also maintained specific features of gene organisation and sequence. This includes the occurrence of closely linked downstream genes, initially identified as a readthrough fusion protein with mammalian paralemmin-2 (Palm2-AKAP2). We have found evidence for such an arrangement for paralemmin-1 and -2 in several vertebrate genomes, as well as for palmdelph