title: Evolutionary history of the reprimo tumor suppressor gene family in vertebrates with a description of a new reprimo gene lineage.
abstract: Genes related to human diseases should be natural targets for evolutionary studies, since they could provide clues regarding the genetic bases of pathologies and potential treatments. Here we studied the evolution of the reprimo gene family, a group of tumor-suppressor genes that are implicated in p53-mediated cell cycle arrest. These genes, especially the reprimo duplicate located on human chromosome 2, have been associated with epigenetic modifications correlated with transcriptional silencing and cancer progression. We demonstrate the presence of a third reprimo lineage that, together with the reprimo and reprimo-like genes, appears to have been differentially retained during the evolutionary history of vertebrates. We present evidence that these reprimo lineages originated early in vertebrate evolution and expanded as a result of the two rounds of whole genome duplications that occurred in the last common ancestor of vertebrates. The reprimo gene has been lost in birds, and the third reprimo gene lineage has been retained in only a few distantly related species, such as coelacanth and gar. Expression analyses revealed that the reprimo paralogs are mainly expressed in the nervous system. Different vertebrate lineages have retained different reprimo paralogs, and even in species that have retained multiple copies, only one of them is heavily expressed.
authors.affiliation: Advanced Center for Chronic Diseases (ACCDiS), Pontificia Universidad Católica de Chile, Santiago, Chile; Departamento de Oncología y Hematología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Ignacio A
authors.initials: IA
authors.lastname: Wichmann
authors.affiliation: Instituto de Ciencias Ambientales y Evolutivas, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Kattina
authors.initials: K
authors.lastname: Zavala
authors.affiliation: Department of Biochemistry, Molecular Biology, Entomology, and Plant Pathology, Mississippi State University, MS, USA; Institute for Genomics, Biocomputing, and Biotechnology, Mississippi State University, MS, USA.
authors.forename: Federico G
authors.initials: FG
authors.lastname: Hoffmann
authors.affiliation: Department of Biochemistry, Molecular Biology, Entomology, and Plant Pathology, Mississippi State University, MS, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Vandewege
authors.affiliation: Advanced Center for Chronic Diseases (ACCDiS), Pontificia Universidad Católica de Chile, Santiago, Chile; Departamento de Oncología y Hematología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; Center UC for Investigation in Oncology (CITO), Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Alejandro H
authors.initials: AH
authors.lastname: Corvalán
authors.affiliation: Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Julio D
authors.initials: JD
authors.lastname: Amigo
authors.affiliation: Advanced Center for Chronic Diseases (ACCDiS), Pontificia Universidad Católica de Chile, Santiago, Chile; Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile; Center UC for Investigation in Oncology (CITO), Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Gareth I
authors.initials: GI
authors.lastname: Owen
authors.affiliation: Instituto de Ciencias Ambientales y Evolutivas, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile. Electronic address: jopazo@gmail.com.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Opazo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics*; D019143:Evolution, Molecular; D020440:Gene Duplication; D016147:Genes, Tumor Suppressor; D006801:Humans; D016013:Likelihood Functions; D005810:Multigene Family; D010802:Phylogeny; D016415:Sequence Alignment; D026801:Synteny / Q000235:genetics; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics; D014714:Vertebrates / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins
keywords: Cancer; Evolutionary medicine; Gastric cancer; Gene family evolution; Whole genome duplication