The evolution of the glandular kallikrein locus: Identification of orthologs and pseudogenes in the cotton-top tamarin Journal Article

Authors: Olsson, A. Y.; Valtonen-André, C.; Lilja, H.; Lundwall, Å
Article Title: The evolution of the glandular kallikrein locus: Identification of orthologs and pseudogenes in the cotton-top tamarin
Abstract: Comparisons of the glandular kallikreins loci in human, mouse and rat revealed remarkable differences. For example, the mouse and the rat lack the genes encoding prostate-specific antigen (PSA) and human glandular kallikrein 2 (hK2). In contrast, the intergenic region between KLK1 and KLK15 is devoid of genes and spans only 1.5 kb in humans, but encompasses 23 KLK1-like genes spanning 290 kb in the mouse. To further elucidate the evolution of glandular kallikrein genes, we investigated the structure and organization of these genes in the cotton-top tamarin (Saguinus oedipus), a New World monkey. We conclude that this species has no PSA gene. Moreover, the ortholog of the hK2 gene is a pseudogene, as it contains several mutations that preclude formation of a functional serine protease. The expression of this gene was probably silenced by a 15-bp deletion observed in an androgen response element in the upstream promoter region. Replacing the deleted base pairs in vitro with nucleotides from the human counterpart dramatically restored the transcriptional activity to a level that even surpassed that of the human ortholog. We also determined the nucleotide sequence of KLK15 and the intergenic region between this gene and KLK1 in the cotton-top tamarin. The region between KLK1 and KLK15 is conserved between the cotton-top tamarin and humans, and there are no signs of the extension seen in the mouse. KLK15 appeared to be functional, thus, we predict that it generates a protease with specificity similar to that of the human ortholog. © 2004 Elsevier B.V. All rights reserved.
Keywords: gene deletion; nonhuman; prostate specific antigen; animals; mice; gene expression; gene locus; evolution; genetic transcription; transcription, genetic; evolution, molecular; prostate-specific antigen; amino acid sequence; conserved sequence; molecular sequence data; gene identification; nucleotide sequence; base sequence; rats; gene silencing; luciferases; kallikreins; gene structure; 5' untranslated regions; phylogeny; tissue kallikrein; tissue kallikreins; enhancer; pseudogene; pseudogenes; humans; human; priority journal; article; are; anthropoidea; saguinus; gossypium hirsutum; platyrrhini; saguinus imperator; saguinus oedipus
Journal Title: Gene
Volume: 343
Issue: 2
ISSN: 0378-1119
Publisher: Elsevier Science, Inc.  
Date Published: 2004-12-22
Start Page: 347
End Page: 355
Language: English
DOI: 10.1016/j.gene.2004.09.020
PROVIDER: scopus
PUBMED: 15588589
Notes: Gene -- Cited By (since 1996):16 -- Export Date: 16 June 2014 -- CODEN: GENED -- Molecular Sequence Numbers: GENBANK: AF173845, AF556462, AY556462; -- Source: Scopus
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MSK Authors
  1. Hans Gosta Lilja
    286 Lilja