title: Identification of a new genomic hot spot of evolutionary diversification of protein function.
abstract: Establishment of phylogenetic relationships remains a challenging task because it is based on computational analysis of genomic hot spots that display species-specific sequence variations. Here, we identify a species-specific thymine-to-guanine sequence variation in the Glrb gene which gives rise to species-specific splice donor sites in the Glrb genes of mouse and bushbaby. The resulting splice insert in the receptor for the inhibitory neurotransmitter glycine (GlyR) conveys synaptic receptor clustering and specific association with a particular synaptic plasticity-related splice variant of the postsynaptic scaffold protein gephyrin. This study identifies a new genomic hot spot which contributes to phylogenetic diversification of protein function and advances our understanding of phylogenetic relationships.
authors.affiliation: RNA editing and Hyperexcitability Disorders Group, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Aline
authors.initials: A
authors.lastname: Winkelmann
authors.affiliation: Laboratory of Functional and Medical Genomics, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Xiantian
authors.initials: X
authors.lastname: You
authors.affiliation: Department of Biochemistry, University of Cologne and Center for Molecular Medicine, Cologne, Germany.
authors.forename: Nora
authors.initials: N
authors.lastname: Grünewald
authors.affiliation: Department of Neurosurgery, University of Freiburg, Freiburg, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Häussler
authors.affiliation: Department of Neurology, Bern University Hospital, Bern, Switzerland.
authors.forename: Heinz
authors.initials: H
authors.lastname: Krestel
authors.affiliation: Department of Neurosurgery, University of Freiburg, Freiburg, Germany.
authors.forename: Carola A
authors.initials: CA
authors.lastname: Haas
authors.affiliation: Department of Biochemistry, University of Cologne and Center for Molecular Medicine, Cologne, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Schwarz
authors.affiliation: Laboratory of Functional and Medical Genomics, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: RNA editing and Hyperexcitability Disorders Group, Max Delbrück Center for Molecular Medicine, Berlin, Germany; Life Science Department, Zoological Institute, Division of Cell Physiology, TU Braunschweig, Braunschweig, Germany.
authors.forename: Jochen C
authors.initials: JC
authors.lastname: Meier
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005701:Galago / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D014644:Genetic Variation; D016678:Genome; D007438:Introns; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D010802:Phylogeny; D018009:Receptors, Glycine / Q000235:genetics* / Q000378:metabolism; D013045:Species Specificity; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D002352:Carrier Proteins; C491949:Glrb protein, mouse; D008565:Membrane Proteins; D018009:Receptors, Glycine; C073441:gephyrin