Analysis of prostate-specific antigen transcripts in chimpanzees, cynomolgus monkeys, baboons, and African green monkeys.

James N Mubiru,Robert E Shade,Michael Owston,Edward J Dick,Magdalena Garcia-Forey,Carolina B Livi,Jeffrey Rogers,Christian Olsen,Alice S Yang,Sudhir Nayak

doi:10.1371/journal.pone.0094522

Abstract

The function of prostate-specific antigen (PSA) is to liquefy the semen coagulum so that the released sperm can fuse with the ovum. Fifteen spliced variants of the PSA gene have been reported in humans, but little is known about alternative splicing in nonhuman primates. Positive selection has been reported in sex- and reproductive-related genes from sea urchins to Drosophila to humans; however, there are few studies of adaptive evolution of the PSA gene. Here, using polymerase chain reaction (PCR) product cloning and sequencing, we study PSA transcript variant heterogeneity in the prostates of chimpanzees (Pan troglodytes), cynomolgus monkeys (Macaca fascicularis), baboons (Papio hamadryas anubis), and African green monkeys (Chlorocebus aethiops). Six PSA variants were identified in the chimpanzee prostate, but only two variants were found in cynomolgus monkeys, baboons, and African green monkeys. In the chimpanzee the full-length transcript is expressed at the same magnitude as the transcripts that retain intron 3. We have found previously unidentified splice variants of the PSA gene, some of which might be linked to disease conditions. Selection on the PSA gene was studied in 11 primate species by computational methods using the sequences reported here for African green monkey, cynomolgus monkey, baboon, and chimpanzee and other sequences available in public databases. A codon-based analysis (dN/dS) of the PSA gene identified potential adaptive evolution at five residue sites (Arg45, Lys70, Gln144, Pro189, and Thr203).

Highlights

Prostate-specific antigen (PSA) is encoded by the kallikrein-3 (KLK3) gene, which belongs to the tissue kallikrein (KLK) gene family; the official name of the gene is KLK3, it is commonly referred to as PSA [1,2]
To the best of our knowledge, this study is the first to report the African green monkey PSA mRNA sequence and the first to report on alternative splicing of the PSA gene in nonhuman primates
It is important to note that the identification of alternative splice variants depends on the primers used, and we cannot rule out the possibility that there are other splice variants not found by our cloning primers

Summary

Introduction

Prostate-specific antigen (PSA) is encoded by the kallikrein-3 (KLK3) gene, which belongs to the tissue kallikrein (KLK) gene family; the official name of the gene is KLK3, it is commonly referred to as PSA [1,2]. The PSA gene is composed of five exons and four introns. Part of the first exon codes for a signal peptide that targets the protein for secretion [3,4]. In the PSA protein, residues His, Asp102, and Ser195 have been reported to be important for proteolytic activity of PSA and other kallikreins, and they are commonly referred to as the catalytic triad [5,6]. PSA has an activation peptide of seven amino acids that is cleaved by KLK2 protein to generate enzymatically active PSA [7,8]. Great apes, and Old World monkeys this is done by PSA [3,11,12,13,14]

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