Dataset Information

The secretin gene: evolutionary history, alternative splicing, and developmental regulation.

ABSTRACT: The gene encoding the hormone secretin has been isolated and structurally characterized. The transcriptional unit is divided into four exons spanning 813 nucleotides. Comparison of the rat secretin gene to the other members of the glucagon-secretin gene family reveals that similarities are restricted to the exons encoding the biologically active peptides. Analysis of RNA from porcine intestine indicates that at least two transcripts are generated from the porcine secretin gene as a result of differential splicing. The longer and more abundant transcript appears to be identical to a previously isolated cDNA, which encodes a precursor that includes a 72-amino acid C-terminal extension peptide. The shorter transcript does not contain the third exon and, as a result, encodes only 44 residues beyond the C terminus of secretin. The amino acid sequence deduced from the shorter transcript is identical to a precursor form of secretin recently isolated from porcine duodenum [Gafvelin, G., Jornvall, H. & Mutt, V. (1990) Proc. Natl. Acad. Sci. USA 87, 6781-6785]. Developmental studies reveal that both secretin mRNA and peptide levels in the intestine are highest just before birth, prior to the onset of gastric acid secretion and feeding. This observation implies that secretin biosynthesis in developing animals is controlled independently of the principal factors known to regulate secretin release in adult animals.

SUBMITTER: Kopin AS

PROVIDER: S-EPMC51867 | biostudies-other | 1991 Jun

REPOSITORIES: biostudies-other

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The secretin gene: evolutionary history, alternative splicing, and developmental regulation.

Kopin A S AS Wheeler M B MB Nishitani J J McBride E W EW Chang T M TM Chey W Y WY Leiter A B AB

Proceedings of the National Academy of Sciences of the United States of America 19910601 12

The gene encoding the hormone secretin has been isolated and structurally characterized. The transcriptional unit is divided into four exons spanning 813 nucleotides. Comparison of the rat secretin gene to the other members of the glucagon-secretin gene family reveals that similarities are restricted to the exons encoding the biologically active peptides. Analysis of RNA from porcine intestine indicates that at least two transcripts are generated from the porcine secretin gene as a result of dif ...[more]

PMID: 1711228

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Project description:BackgroundAlternatively spliced exons play an important role in the diversification of gene function in most metazoans and are highly regulated by conserved motifs in exons and introns. Two contradicting properties have been associated to evolutionary conserved alternative exons: higher sequence conservation and higher rate of non-synonymous substitutions, relative to constitutive exons. In order to clarify this issue, we have performed an analysis of the evolution of alternative and constitutive exons, using a large set of protein coding exons conserved between human and mouse and taking into account the conservation of the transcript exonic structure. Further, we have also defined a measure of the variation of the arrangement of exonic splicing enhancers (ESE-conservation score) to study the evolution of splicing regulatory sequences. We have used this measure to correlate the changes in the arrangement of ESEs with the divergence of exon and intron sequences.ResultsWe find evidence for a relation between the lack of conservation of the exonic structure and the weakening of the sequence evolutionary constraints in alternative and constitutive exons. Exons in transcripts with non-conserved exonic structures have higher synonymous (dS) and non-synonymous (dN) substitution rates than exons in conserved structures. Moreover, alternative exons in transcripts with non-conserved exonic structure are the least constrained in sequence evolution, and at high EST-inclusion levels they are found to be very similar to constitutive exons, whereas alternative exons in transcripts with conserved exonic structure have a dS significantly lower than average at all EST-inclusion levels. We also find higher conservation in the arrangement of ESEs in constitutive exons compared to alternative ones. Additionally, the sequence conservation at flanking introns remains constant for constitutive exons at all ESE-conservation values, but increases for alternative exons at high ESE-conservation values.ConclusionWe conclude that most of the differences in dN observed between alternative and constitutive exons can be explained by the conservation of the transcript exonic structure. Low dS values are more characteristic of alternative exons with conserved exonic structure, but not of those with non-conserved exonic structure. Additionally, constitutive exons are characterized by a higher conservation in the arrangement of ESEs, and alternative exons with an ESE-conservation similar to that of constitutive exons are characterized by a conservation of the flanking intron sequences higher than average, indicating the presence of more intronic regulatory signals.

Dataset Information

The secretin gene: evolutionary history, alternative splicing, and developmental regulation.

Publications

The secretin gene: evolutionary history, alternative splicing, and developmental regulation.

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