MBE Advance Access originally published online on June 27, 2003
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Mol. Biol. Evol. 20(10):1669-1674. 2003
DOI: 10.1093/molbev/msg191
© 2003 by the Society for Molecular Biology and Evolution. ISSN: 0737-4038
Remarkable Sequence Conservation of the Last Intron in the PKD1 Gene
* Department of Biochemistry and Molecular Biology, and the Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas
Department of Chemistry/Physics, Northwest Missouri State University, Maryville, Missouri
E-mail: jcalvet{at}kumc.edu.
The last intron of the PKD1 gene (intron 45) was found to have exceptionally high sequence conservation across four mammalian species: human, mouse, rat, and dog. This conservation did not extend to the comparable intron in pufferfish. Pairwise comparisons for intron 45 showed 91% identity (human vs. dog) to 100% identity (mouse vs. rat) for an average for all four species of 94% identity. In contrast, introns 43 and 44 of the PKD1 gene had average pairwise identities of 57% and 54%, and exons 43, 44, and 45 and the coding region of exon 46 had average pairwise identities of 80%, 84%, 82%, and 80%. Intron 45 is 90 to 95 bp in length, with the major region of sequence divergence being in a central 4-bp to 9-bp variable region. RNA secondary structure analysis of intron 45 predicts a branching stem-loop structure in which the central variable region lies in one loop and the putative branch point sequence lies in another loop, suggesting that the intron adopts a specific stem-loop structure that may be important for its removal. Although intron 45 appears to conform to the class of small, G-triplet–containing introns that are spliced by a mechanism utilizing intron definition, its high sequence conservation may be a reflection of constraints imposed by a unique mechanism that coordinates splicing of this last PKD1 intron with polyadenylation.
Key Words: polycystic kidney disease • intron • G-triplet • splicing