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The PCNA pseudogenes in the human genome.

ABSTRACT: BACKGROUND: The proliferating cell nuclear antigen (PCNA) is a key protein in the eukaryotic DNA replication and cell proliferation. Following the cloning and characterisation of the human PCNA gene, the question of the existence of pseudogenes in the human genome was raised. FINDINGS: In this short communication we summarise the existing information about the PCNA pseudogenes and critically assess their status. CONCLUSIONS: We propose the existence of at least four valid PCNA pseudogenes, PCNAP1, PCNAP2, LOC392454 and LOC390102. We would like to recommend assignment of a name for LOC392454 as "proliferating cell nuclear antigen pseudogene 3" (alias PCNAP3) and a name for LOC390102 as "proliferating cell nuclear antigen pseudogene 4" (alias PCNAP4). We prompt for more critical evaluation of the existence of a PCNA pseudogene, designated as PCNAP.

SUBMITTER: Stoimenov I

PROVIDER: S-EPMC3296674 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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The PCNA pseudogenes in the human genome.

Stoimenov Ivaylo I Lagerqvist Anne A

BMC research notes 20120206

<h4>Background</h4>The proliferating cell nuclear antigen (PCNA) is a key protein in the eukaryotic DNA replication and cell proliferation. Following the cloning and characterisation of the human PCNA gene, the question of the existence of pseudogenes in the human genome was raised.<h4>Findings</h4>In this short communication we summarise the existing information about the PCNA pseudogenes and critically assess their status.<h4>Conclusions</h4>We propose the existence of at least four valid PCNA ...[more]

PMID: 22309575

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Project description:Mammals have 79 ribosomal proteins (RP). Using a systematic procedure based on sequence-homology, we have comprehensively identified pseudogenes of these proteins in the human genome. Our assignments are available at http://www.pseudogene.org or http://bioinfo.mbb.yale.edu/genome/pseudogene. In total, we found 2090 processed pseudogenes and 16 duplications of RP genes. In relation to the matching parent protein, each of the processed pseudogenes has an average relative sequence length of 97% and an average sequence identity of 76%. A small number (258) of them do not contain obvious disablements (stop codons or frameshifts) and, therefore, could be mistaken as functional genes, and 178 are disrupted by one or more repetitive elements. On average, processed pseudogenes have a longer truncation at the 5' end than the 3' end, consistent with the target-primed-reverse-transcription (TPRT) mechanism. Interestingly, on chromosome 16, an RPL26 processed pseudogene was found in the intron region of a functional RPS2 gene. The large-scale distribution of RP pseudogenes throughout the genome appears to result, chiefly, from random insertions with the numbers on each chromosome, consequently, proportional to its size. In contrast to RP genes, the RP pseudogenes have the highest density in GC-intermediate regions (41%-46%) of the genome, with the density pattern being between that of LINEs and Alus. This can be explained by a negative selection theory as we observed that GC-rich RP pseudogenes decay faster in GC-poor regions. Also, we observed a correlation between the number of processed pseudogenes and the GC content of the associated functional gene, i.e., relatively GC-poor RPs have more processed pseudogenes. This ranges from 145 pseudogenes for RPL21 down to 3 pseudogenes for RPL14. We were able to date the RP pseudogenes based on their sequence divergence from present-day RP genes, finding an age distribution similar to that for Alus. The distribution is consistent with a decline in retrotransposition activity in the hominid lineage during the last 40 Myr. We discuss the implications for retrotransposon stability and genome dynamics based on these new findings.

Project description:Pseudogenes are copies of genes that cannot produce a protein. They can be detected from disruptions to their apparent coding sequence, caused by frameshifts and premature stop codons. They are classed as either processed pseudogenes (made by reverse transcription from an mRNA) or duplicated pseudogenes, arising from duplication in the genomic DNA and subsequent disablement. Historically, there is anecdotal evidence that the fruit fly (Drosophila melanogaster) has few pseudogenes. Investigators have linked this to a high deletion rate of genomic DNA, for which there is evidence from genetic experiments on genome size. Here, we apply a homology-based pipeline that was developed previously to identify pseudogenes in other eukaryotic genomes, to the fruit fly, so as to derive the first complete survey of its pseudogene population. We find approximately 100 pseudogenes, with at least a sixth of these as candidate processed pseudogenes. This gives a much lower proportion of pseudogenes (compared with the size of the proteome) than in the genomes of other eukaryotes for which data are available (human, nematode and budding yeast). Closest matching proteins to Drosophila pseudogenes are significantly longer than the average protein in its proteome (up to approximately 60% more than the average protein's length), in contrast to the situation in the three other eukaryotic genomes. This may be due to the persistence of fragments of longer genes. In the fly pseudogene population, we found most pseudogenes for serine proteases (which are more abundant in the Drosophila lineage compared with the other eukaryotes), immunoglobulin-motif-containing proteins and cytochromes P450. Data on the sequences and positions of the putative pseudogenes are available at: http://www.pseudogene.org/fly. The detection of a small number of pseudogenes in the Drosophila genome and the higher mean length for the closest matching proteins to pseudogenes (possibly because remnants of genes encoding longer proteins are more likely to persist) are further evidence for a high deletion rate of genomic DNA in the fruit fly. The data are useful for molecular evolution study in Drosophila.

Dataset Information

The PCNA pseudogenes in the human genome.

Publications

The PCNA pseudogenes in the human genome.

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