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PLoS One
2014 Apr 14;94:e94522. doi: 10.1371/journal.pone.0094522.
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Analysis of prostate-specific antigen transcripts in chimpanzees, cynomolgus monkeys, baboons, and African green monkeys.
Mubiru JN
,
Yang AS
,
Olsen C
,
Nayak S
,
Livi CB
,
Dick EJ
,
Owston M
,
Garcia-Forey M
,
Shade RE
,
Rogers J
.
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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).
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Figure 1. Structure of the PSA variants identified in cynomolgus monkey, baboon, African green monkey, and chimpanzee prostates.The retained intronic sequences are shown in blue, and the missing parts of exons are shown by blank boxes. The molecular weight (MW) and open reading frame (ORF) length of each predicted translation product were determined using the computational tool located at the EXPASY website (http://expasy.org/) and are shown to the right of the corresponding transcript. The residues that make up the catalytic triad are shown by asterisks.
Figure 2. Alignment of the predicted amino acid sequences of the PSA-1 transcripts (panel A) and PSA-2 transcripts (panel B).The signal peptide is indicated in red italics. The residues that make up the catalytic triad are in blue and are indicated by arrows. The activation sequence is in bold and underlined. The unique 16-residue sequence that emanates from use of intron 3 is shown in green bold italic. The alignments were carried out using the CLUTALW program available at http://www.ebi.ac.uk/toolsmsa/clustalw2/ (Thompson et al., 1994 [41]).
Figure 3. Relative real-time PCR quantitation of chimpanzee transcripts that use intron 3 sequences compared to those that do not (mean ± standard deviation, n = 3).Individual tissue samples were reverse-transcribed and PSA transcript mRNA was quantitated using the primer/probe sets described in Table 2. Relative levels of the PSA variants were normalized to the 18s RNA levels in the same samples.
Figure 4. Multiple sequence comparison by log expectation (MUSCLE) program guided alignments of PSA-1 transcripts from 11 species.The codons that are under positive selection are indicated by arrows. Fully conserved residues are indicated by asterisks, partly conserved residues by colons, and weakly conserved residues by periods. The species' complete scientific names are as follows: Pan troglodytes, Pan paniscus, Homo sapiens, Pongo pygmaeus, Gorilla gorilla, Nomascus leucogenys, Macaca fascicularis, Macaca fuscata, Macaca mulatta, Papio hamadryas anubis, and Chlorocebus aethiops.
Figure 5. Phylogenetic tree constructed using neighbor-joining, maximum parsimony, maximum-likelihood, and unweighted pair group method with arithmetic mean (UPGMA) methods provided in the Phylip package, version 3.695.The numbers at each node are bootstraps, and the numbers in red on top of each branch are dN/dS values for that branch.
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