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MBE Advance Access published online on June 27, 2003
Molecular Biology and Evolution, doi:10.1093/molbev/msg191
Molecular Biology and Evolution © Society for Molecular Biology and Evolution 2003; all rights reserved
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Accepted May 29, 2003
© 2003 Society for Molecular Biology and Evolution

Original Articles

Remarkable Sequence Conservation of the Last Intron in the PKD1 Gene

Marianna Rodova 1, M. Rafiq Islam 2, Kenneth R. Peterson 1, and James P. Calvet 1*

1 Department of Biochemistry and Molecular Biology, and the Kidney Institute, University of Kansas Medical Center, Kansas City, KS
2 Department of Biochemistry and Molecular Biology, and the Kidney Institute, University of Kansas Medical Center, Kansas City, KS; Department of Chemistry/Physics, Northwest Missouri State University, Maryville, MO

* To whom correspondence should be addressed. E-mail: jcalvet{at}kumc.edu.


  Abstract

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, 45, and the coding region of exon 46 had average pairwise identities of 80%, 84%, 82%, and 80%. Intron 45 is 90-95 bp in length, with the major region of sequence divergence being in a central 4-9 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. While intron 45 appears to conform with 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


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