title: Evolutionary forces shape the human RFPL1,2,3 genes toward a role in neocortex development.
abstract: The size and organization of the brain neocortex has dramatically changed during primate evolution. This is probably due to the emergence of novel genes after duplication events, evolutionary changes in gene expression, and/or acceleration in protein evolution. Here, we describe a human Ret finger protein-like (hRFPL)1,2,3 gene cluster on chromosome 22, which is transactivated by the corticogenic transcription factor Pax6. High hRFPL1,2,3 transcript levels were detected at the onset of neurogenesis in differentiating human embryonic stem cells and in the developing human neocortex, whereas the unique murine RFPL gene is expressed in liver but not in neural tissue. Study of the evolutionary history of the RFPL gene family revealed that the RFPL1,2,3 gene ancestor emerged after the Euarchonta-Glires split. Subsequent duplication events led to the presence of multiple RFPL1,2,3 genes in Catarrhini ( approximately 34 mya) resulting in an increase in gene copy number in the hominoid lineage. In Catarrhini, RFPL1,2,3 expression profile diverged toward the neocortex and cerebellum over the liver. Importantly, humans showed a striking increase in cortical RFPL1,2,3 expression in comparison to their cerebellum, and to chimpanzee and macaque neocortex. Acceleration in RFPL-protein evolution was also observed with signs of positive selection in the RFPL1,2,3 cluster and two neofunctionalization events (acquisition of a specific RFPL-Defining Motif in all RFPLs and of a N-terminal 29 amino-acid sequence in catarrhinian RFPL1,2,3). Thus, we propose that the recent emergence and multiplication of the RFPL1,2,3 genes contribute to changes in primate neocortex size and/or organization.
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Rue Michel-Servet 1, 1211 Geneva, Switzerland. jerome.bonnefont@medecine.unige.ch
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bonnefont
authors.forename: Sergey I
authors.initials: SI
authors.lastname: Nikolaev
authors.forename: Anselme L
authors.initials: AL
authors.lastname: Perrier
authors.forename: Song
authors.initials: S
authors.lastname: Guo
authors.forename: Laetitia
authors.initials: L
authors.lastname: Cartier
authors.forename: Silvia
authors.initials: S
authors.lastname: Sorce
authors.forename: Térèse
authors.initials: T
authors.lastname: Laforge
authors.forename: Laetitia
authors.initials: L
authors.lastname: Aubry
authors.forename: Philipp
authors.initials: P
authors.lastname: Khaitovich
authors.forename: Marc
authors.initials: M
authors.lastname: Peschanski
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Antonarakis
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Krause
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis*; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000166:cytology; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D006367:HeLa Cells; D006801:Humans; D008099:Liver / Q000378:metabolism; D008251:Macaca; D019579:Neocortex / Q000196:embryology* / Q000378:metabolism; D002679:Pan troglodytes
chemical_list: D002352:Carrier Proteins; C400217:RFPL1 protein, human; C400218:RFPL2 protein, human; C400219:RFPL3 protein, human