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Identification and analysis of over 2000 ribosomal protein pseudogenes in the human genome.

ABSTRACT: 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.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC187539 | biostudies-literature | 2002 Oct

REPOSITORIES: biostudies-literature

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Identification and analysis of over 2000 ribosomal protein pseudogenes in the human genome.

Zhang Zhaolei Z Harrison Paul P Gerstein Mark M

Genome research 20021001 10

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 ...[more]

PMID: 12368239

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Project description:BackgroundRibosomal proteins (RPs) have about 2000 pseudogenes in the human genome. While anecdotal reports for RP pseudogene transcription exists, it is unclear to what extent these pseudogenes are transcribed. The RP pseudogene transcription is difficult to identify in microarrays due to potential cross-hybridization between transcripts from the parent genes and pseudogenes. Recently, transcriptome sequencing (RNA-seq) provides an opportunity to ascertain the transcription of pseudogenes. A challenge for pseudogene expression discovery in RNA-seq data lies in the difficulty to uniquely identify reads mapped to pseudogene regions, which are typically also similar to the parent genes.ResultsHere we developed a specialized pipeline for pseudogene transcription discovery. We first construct a "composite genome" that includes the entire human genome sequence as well as mRNA sequences of real ribosomal protein genes. We then map all sequence reads to the composite genome, and only exact matches were retained. Moreover, we restrict our analysis to strictly defined mappable regions and calculate the RPKM values as measurement of pseudogene transcription levels. We report evidences for the transcription of RP pseudogenes in 16 human tissues. By analyzing the Human Body Map 2.0 study RNA-sequencing data using our pipeline, we identified that one ribosomal protein (RP) pseudogene (PGOHUM-249508) is transcribed with RPKM 170 in thyroid. Moreover, three other RP pseudogenes are transcribed with RPKM > 10, a level similar to that of the normal RP genes, in white blood cell, kidney, and testes, respectively. Furthermore, an additional thirteen RP pseudogenes are of RPKM > 5, corresponding to the 20-30 percentile among all genes. Unlike ribosomal protein genes that are constitutively expressed in almost all tissues, RP pseudogenes are differentially expressed, suggesting that they may contribute to tissue-specific biological processes.ConclusionsUsing a specialized bioinformatics method, we identified the transcription of ribosomal protein pseudogenes in human tissues using RNA-seq data.

Project description:We have developed an initial approach for annotating and surveying pseudogenes in the human genome. We search human genomic DNA for regions that are similar to known protein sequences and contain obvious disablements (i.e., mid-sequence stop codons or frameshifts), while ensuring minimal overlap with annotations of known genes. Pseudogenes can be divided into "processed" and "nonprocessed"; the former are reverse transcribed from mRNA (and therefore have no intron structure), whereas the latter presumably arise from genomic duplications. We annotate putative processed pseudogenes based on whether there is a continuous span of homology that is >70% of the length of the closest matching human protein (i.e., with introns removed), or whether there is evidence of polyadenylation. We have applied our approach to chromosomes 21 and 22, the first parts of the human genome completely sequenced, finding 190 new pseudogene annotations beyond the 264 reported by the sequencing centers. In total, on chromosomes 21 and 22, there are 189 processed pseudogenes, 195 nonprocessed pseudogenes, and, additionally, 70 pseudogenic immunoglobulin gene segments. (Detailed assignments are available at http://bioinfo.mbb.yale.edu/genome/pseudogene or http://genecensus.org/pseudogene.) By extrapolation, we predict that there could be up to approximately 20,000 pseudogenes in the whole human genome, with a little more than half of them processed. We have determined the main populations and clusters of pseudogenes on chromosomes 21 and 22. There are notable excesses of pseudogenes relative to genes near the centromeres of both chromosomes, indicating the existence of pseudogenic "hot-spots" in the genome. We have looked at the distribution of InterPro families and Gene Ontology (GO) functional categories in our pseudogenes. Overall, the families in both processed and nonprocessed pseudogene populations occur according to a similar power-law distribution as that found for the occurrence of gene families, with a few big families and many small ones. The processed population is, in particular, enriched in highly expressed ribosomal-protein sequences (approximately 20%), which appear fairly evenly distributed across the chromosomes. We compared processed pseudogenes of different evolutionary ages, observing a high degree of similarity between "ancient" and "modern" subpopulations. This may be attributable to the consistently high expression of ribosomal proteins over evolutionary time. Finally, we find that chromosome 22 pseudogene population is dominated by immunoglobulin segments, which have a greater rate of disablement per amino acid than the other pseudogene populations and are also substantially more diverged.

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

Identification and analysis of over 2000 ribosomal protein pseudogenes in the human genome.

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Identification and analysis of over 2000 ribosomal protein pseudogenes in the human genome.

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