Identification of a new genomic hot spot of evolutionary diversification of protein function

Aline Winkelmann; Xiantian You; Nora Grünewald; Ute Häussler; Heinz Krestel; Carola A Haas; Günter Schwarz; Wei Chen; Jochen C Meier

doi:10.1371/journal.pone.0125413

Identification of a new genomic hot spot of evolutionary diversification of protein function

PLoS One. 2015 May 8;10(5):e0125413. doi: 10.1371/journal.pone.0125413. eCollection 2015.

Authors

Aline Winkelmann¹, Xiantian You², Nora Grünewald³, Ute Häussler⁴, Heinz Krestel⁵, Carola A Haas⁴, Günter Schwarz³, Wei Chen², Jochen C Meier⁶

Affiliations

¹ RNA editing and Hyperexcitability Disorders Group, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
² Laboratory of Functional and Medical Genomics, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
³ Department of Biochemistry, University of Cologne and Center for Molecular Medicine, Cologne, Germany.
⁴ Department of Neurosurgery, University of Freiburg, Freiburg, Germany.
⁵ Department of Neurology, Bern University Hospital, Bern, Switzerland.
⁶ 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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alternative Splicing
Amino Acid Sequence
Animals
Base Sequence
Biological Evolution*
Carrier Proteins / genetics*
Carrier Proteins / metabolism
Exons
Galago / classification
Galago / genetics*
Galago / metabolism
Gene Expression
Genetic Variation
Genome*
Introns
Membrane Proteins / genetics*
Membrane Proteins / metabolism
Mice / classification
Mice / genetics*
Mice / metabolism
Molecular Sequence Data
Neuronal Plasticity
Neurons / metabolism
Neurons / ultrastructure
Phylogeny
Receptors, Glycine / genetics*
Receptors, Glycine / metabolism
Species Specificity
Spinal Cord / cytology
Spinal Cord / metabolism
Synapses / metabolism
Synapses / ultrastructure

Substances

Carrier Proteins
Glrb protein, mouse
Membrane Proteins
Receptors, Glycine
gephyrin

Grants and funding

This work was funded by Bundesministerium für Bildung und Forschung BMBF, grant No. CIPRESS (http://www.neuron-eranet.eu/en/317.php); and Helmholtz Association, grant No. VH-NG-246 (http://www.helmholtz.de/en/home). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.