Magic roundabout is an endothelial-specific ohnolog of ROBO1 which neo-functionalized to an essential new role in angiogenesis

PloS One
L Huminiecki

Abstract

Magic roundabout (ROBO4) is an unusual endothelial-specific paralog of the family of neuronally-expressed axon guidance receptors called roundabouts. Endothelial cells (ECs), whose uninterrupted sheet delimits the lumen of all vertebrate blood vessels and which are absent from invertebrate species, are a vertebrate-specific evolutionary novelty. Herein, the evolutionary mechanism of the duplication, retention and divergence of ROBO4 was investigated for the first time. Phylogenetic analyses carried out suggested that ROBO4 is a fast-evolving paralog of ROBO1 formed at the base of vertebrates. The ancestral expression pattern was neuronal. ROBO4 dramatically shifted its expression and became exceptionally specific to ECs. The data-mining of FANTOM5 and ENCODE reveals that ROBO4's endothelial expression arises from a single transcription start site (TSS), conserved in mouse, controlled by a proximal promoter with a complex architecture suggestive of regulatory neo-functionalization. (An analysis of promoter probabilities suggested the architecture was not due to a chance arrangement of TFBSes). Further evidence for the neo-functionalization of ROBO4 comes from the analysis of its protein interactions, the rates of protein evoluti...Continue Reading

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Datasets Mentioned

BETA
TF351053

Methods Mentioned

BETA
ChIP-seq
Assay
GTPase
electrophoretic
immunoprecipitation
transgenic

Software Mentioned

Adobe Illustrator
MUltiple Sequence Comparison by Log - Expectation ( MUSCLE )
RNAseq
TreeViewJ
custom
MySQL
. py
BLAT
TreeBest
R scripts

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