Taxon-specific evolution of glandular kallikrein genes and identification of a progenitor of prostate-specific antigen

• Published in: Genomics (San Diego, Calif.) Vol. 84; no. 1; pp. 147 - 156
• Main Authors: Yvonne Olsson, A, Lilja, Hans, Lundwall, Åke
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.07.2004; Elsevier
• Subjects: Adenocarcinoma - genetics; Animals; Base Sequence; Basic Medicine; Biological and medical sciences; Classification; Duplication; Evolution, Molecular; Fundamental and applied biological sciences. Psychology; Gene Dosage; Gene Expression Regulation, Neoplastic - genetics; Genes. Genome; Genetics of eukaryotes. Biological and molecular evolution; Genome; Humans; Kallikreins - genetics; Locus; Läkemedelskemi; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinal Chemistry; Medicinska och farmaceutiska grundvetenskaper; Mice; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Paralogs; Phylogeny; Prostate-specific antigen; Prostate-Specific Antigen - genetics; Prostatic Neoplasms - genetics; Rat; Rats; Paralogs; Rat; Duplication; ARE; Prostate-specific antigen; Genome; Locus; hK2; PSA; Serine endopeptidases; Enzyme; Genomics; Identification; Prostate specific antigen; Peptidases; Molecular evolution; Tissue kallikrein; Gene; Hydrolases
• ISSN: 0888-7543; 1089-8646; 1089-8646
• DOI: 10.1016/j.ygeno.2004.01.009

In a previous study we demonstrated that repeated duplications of the tissue kallikrein gene ( Klk1) had resulted in 24 paralogs in mouse. Here we demonstrate a different evolution of rat glandular kallikrein genes. Repeated duplications of an ≈30-kb region, encompassing Klk1, Klk15, and Klk2-ps, resulted in 10 copies of each gene, but only the Klk1 paralogs are functional. The number of genes varies also between nonrodent mammals, e.g., there are probably no paralogs to KLK1 in cow and pig, whereas horse could have up to 5. In the dog, the gene encoding the prostatic arginine esterase was identified as an ortholog to the progenitor of the PSA and hK2 genes, and it carries the same conserved androgen-responsive elements directing prostate transcription as these genes. This is highly interesting with respect to animal models of benign prostate hyperplasia and prostate adenocarcinoma—diseases that have been described only in humans and dogs.