Evolution of the neuron-specific alternative splicing product of the c-src proto-oncogene

F. Raulf, S. M. Robertson, M. Schartl

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Abstract

The observation of a slower migrating form of pp60(c-src) in neural tissue of chicken and mouse has recently been shown to be due to an alternative transcript form of the c-src gene (Martinez et al.: Science 237:411-415, 1987; Levy et al.:Mol Cell Biol 7:4142-4145, 1987). An insertion of 18 basepairs between exons 3 and 4, presumed to be due to alternative splicing of a mini-exon, gives rise to six amino acid residues not found in the non-neuronal (termed fibroblastic) form of pp60(c-src). We have addressed the question of the evolutionary origin of the c-src neuronal insert and its functional significance regarding neural-specific expression of the c-src gene. To this end we have investigated whether the c-src gene of a lower vertebrate (the teleost fish Xiphophorus) gives rise to a neural-specific transcript in an analogous manner. We could show that the fish c-src gene does encode for a 'fibroblastic' and a 'neuronal' form of transcript and that the neuronal transcript does indeed arise by way of alternative splicing of a mini-exon. The mini-exon is also 18 basepairs long and we would demonstrate directly that this exon lies within the intron separating exons 3 and 4. For comparative purposes we have examined whether the fish c-yes gene, the member of the src gene family most closely related to c-src, also encodes a neural tissue-specific transcript. No evidence for a second transcript form in brain was obtained. This result suggests that the mini-exon arose within the c-src gene lineage sometime between the src/yes gene duplication event and the divergence of the evolutionary lineage giving rise to the teleost fish. Published genomic sequence of src-related genes in Drosophila and our own results with Hydra demonstrate no intron in these species at the analogous location, consistent with first appearance of this mini-exon sometime between 550 and 400 million years ago.

Original languageEnglish (US)
Pages (from-to)81-88
Number of pages8
JournalJournal of Neuroscience Research
Volume24
Issue number1
Publication statusPublished - 1989

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ASJC Scopus subject areas

  • Neuroscience(all)

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