MBE Advance Access published online on October 13, 2006
Molecular Biology and Evolution, doi:10.1093/molbev/msl147
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1 Department of Oncological Sciences, University of Torino, Strada Provinciale 142 Km 3,95 10060 Candiolo, Torino, Italy; Division of Molecular Angiogenesis, Institute for Cancer Research and Treatment (IRCC), University of Torino, 10060 Candiolo, Torino, Italy
* To whom correspondence should be addressed. Neurexins constitute a family of proteins originally identified as synaptic transmembrane receptors for a spider venom toxin. In mammals the three known Neurexin genes present two alternative promoters which drive the synthesis of a long (
Accepted October 10, 2006
Research Article
Comparative Genome Analysis of the Neurexin Gene Family in Danio rerio: Insights into Their Functions and Evolution
Alberto Rissone 1, Matteo Monopoli 2, Monica Beltrame 3, Federico Bussolino 1 *, Franco Cotelli 2 
, and Marco Arese 1
2 Department of Biology, University of Milano, via Celoria 26 20133 Milano, Italy
3 Department of Biomolecular Sciences and Biotechnologies, University of Milano, via Celoria 26 20133 Milano, Italy
Federico Bussolino, E-mail: federico.bussolino{at}unito.it
Abstract 
) and a short (
) form and contain different sites of alternative splicing which can give rise to thousands of different transcripts. To date, very little is known about the significance of this variability, except for the modulation of binding to some of the Neurexin ligands. Although orthologs of Neurexins have been isolated in invertebrates, these genes have been studied mostly in mammals. With the aim of investigating their functions in lower vertebrates we chose Danio rerio as a model because of its increasing importance in comparative biology. We have isolated six zebrafish homologous genes, which are highly conserved at the structural level and display a similar regulation of alternative splicing, despite about 450 million years separating the human and zebrafish species. Our data indicate a strong selective pressure at the exonic level and on the intronic borders, in particular on the regulative intronic sequences that flank the exons subject to alternative splicing. Such a selective pressure could help conserve the regulation and consequently the function of these genes along the vertebrates evolutive tree. Alternative splicing analysis during development shows that all genes are expressed and finely regulated since the earliest stages of development, but mark an increase after the 24 hour stage, which corresponds to the beginning of synaptogenesis. Moreover, we found that specific isoforms of a zebrafish Neurexin gene (nrxn1a) are expressed in the adult testis and in the earliest stages of development, before the beginning of zygotic transcription, indicating a potential delivery of paternal RNA to the embryo. Our analysis suggests the existence of possible new functions for Neurexins, serving as the basis for novel approaches to the functional studies of this complex neuronal protein family and more in general to the understanding of the alternative splicing mechanism in low vertebrates.These authors contributed equally to the paper.
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