title: The WTX/AMER1 gene family: evolution, signature and function.
abstract: BACKGROUND
  WTX is a novel gene mutated in a proportion of Wilms' tumors and in patients suffering from sclerosing bone dysplasia. On the molecular level WTX has been shown to act as an antagonist of canonical Wnt/β-catenin signaling in fish and mammals thus linking it to an essential pathway involved in normal development and cancer formation. Interestingly, WTX seems to also localize to an intranuclear component called paraspeckles. In spite of the growing interest of molecular biologists in WTX, little is known about its paralogs and its phylogenetic history.
  
  
  RESULTS
  Using the amino-acid sequence of WTX/AMER1 as a tool for the assignment of orthology and paralogy, we here identify two novel proteins, AMER2 and AMER3, as "WTX" related. This Amer gene family is present in all currently available vertebrate genome sequences, but not invertebrate genomes and is characterized by six conserved blocks of sequences. The phylogenetic analysis suggests that the protoAmer gene originated early in the vertebrate lineage and was then duplicated due to whole genome duplications (WGD) giving rise to the three different Amer genes.
  
  
  CONCLUSIONS
  Our study represents the first phylogenetic analysis of Amer genes and reveals a new vertebrate specific gene family that is likely to have played an important role in the evolution of this subphylum. Divergent and conserved molecular functions of Wtx/Amer1, Amer2 and Amer3 are discussed.
authors.affiliation: INSERM, U636, F-06108 Nice, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Boutet
authors.forename: Glenda
authors.initials: G
authors.lastname: Comai
authors.forename: Andreas
authors.initials: A
authors.lastname: Schedl
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002460:Cell Line; D019143:Evolution, Molecular; D020440:Gene Duplication / Q000235:genetics / Q000502:physiology; D006801:Humans; D007448:Invertebrates / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics; D010802:Phylogeny; D011506:Proteins / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*; D014714:Vertebrates / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C517118:AMER1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins; D051176:beta Catenin