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Comparative analysis of processed ribosomal protein pseudogenes in four mammalian genomes.

ABSTRACT: The availability of genome sequences of numerous organisms allows comparative study of pseudogenes in syntenic regions. Conservation of pseudogenes suggests that they might have a functional role in some instances.We report the first large-scale comparative analysis of ribosomal protein pseudogenes in four mammalian genomes (human, chimpanzee, mouse and rat). To this end, we have assigned these pseudogenes in the four organisms using an automated pipeline and make the results available online. Each organism has a large number of ribosomal protein pseudogenes (approximately 1,400 to 2,800). The majority of them are processed (generated by retrotransposition). However, we do not see a correlation between the number of pseudogenes associated with a ribosomal protein gene and its mRNA abundance. Analysis of pseudogenes in syntenic regions between species shows that most are conserved between human and chimpanzee, but very few are conserved between primates and rodents. Interestingly, syntenic pseudogenes have a lower rate of nucleotide substitution than their surrounding intergenic DNA. Moreover, evidence from expressed sequence tags indicates that two pseudogenes conserved between human and mouse are transcribed. Detailed analysis shows that one of them, the pseudogene of RPS27, is likely to be a protein-coding gene. This is significant as previous reports indicated there are exactly 80 ribosomal protein genes encoded by the human genome.Our analysis indicates that processed ribosomal protein pseudogenes abound in mammalian genomes, but few of these are conserved between primates and rodents. This highlights the large amount of recent retrotranspositional activity in mammals and a relatively larger amount of it in the rodent lineage.

SUBMITTER: Balasubramanian S

PROVIDER: S-EPMC2687790 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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Comparative analysis of processed ribosomal protein pseudogenes in four mammalian genomes.

Balasubramanian Suganthi S Zheng Deyou D Liu Yuen-Jong YJ Fang Gang G Frankish Adam A Carriero Nicholas N Robilotto Rebecca R Cayting Philip P Gerstein Mark M

Genome biology 20090105 1

<h4>Background</h4>The availability of genome sequences of numerous organisms allows comparative study of pseudogenes in syntenic regions. Conservation of pseudogenes suggests that they might have a functional role in some instances.<h4>Results</h4>We report the first large-scale comparative analysis of ribosomal protein pseudogenes in four mammalian genomes (human, chimpanzee, mouse and rat). To this end, we have assigned these pseudogenes in the four organisms using an automated pipeline and m ...[more]

PMID: 19123937

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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:Trypanosomatids belong to a remarkable group of unicellular, parasitic organisms of the order Kinetoplastida, an early diverging branch of the phylogenetic tree of eukaryotes, exhibiting intriguing biological characteristics affecting gene expression (intronless polycistronic transcription, trans-splicing, and RNA editing), metabolism, surface molecules, and organelles (compartmentalization of glycolysis, variation of the surface molecules, and unique mitochondrial DNA), cell biology and life cycle (phagocytic vacuoles evasion and intricate patterns of cell morphogenesis). With numerous genomic-scale data of several trypanosomatids becoming available since 2005 (genomes, transcriptomes, and proteomes), the scientific community can further investigate the mechanisms underlying these unusual features and address other unexplored phenomena possibly revealing biological aspects of the early evolution of eukaryotes. One fundamental aspect comprises the processes and mechanisms involved in the acquisition and loss of genes throughout the evolutionary history of these primitive microorganisms. Here, we present a comprehensive in silico analysis of pseudogenes in three major representatives of this group: Leishmania major, Trypanosoma brucei, and Trypanosoma cruzi. Pseudogenes, DNA segments originating from altered genes that lost their original function, are genomic relics that can offer an essential record of the evolutionary history of functional genes, as well as clues about the dynamics and evolution of hosting genomes. Scanning these genomes with functional proteins as proxies to reveal intergenic regions with protein-coding features, relying on a customized threshold to distinguish statistically and biologically significant sequence similarities, and reassembling remnant sequences from their debris, we found thousands of pseudogenes and hundreds of open reading frames, with particular characteristics in each trypanosomatid: mutation profile, number, content, density, codon bias, average size, single- or multi-copy gene origin, number and type of mutations, putative primitive function, and transcriptional activity. These features suggest a common process of pseudogene formation, different patterns of pseudogene evolution and extant biological functions, and/or distinct genome organization undertaken by those parasites during evolution, as well as different evolutionary and/or selective pressures acting on distinct lineages.

Dataset Information

Comparative analysis of processed ribosomal protein pseudogenes in four mammalian genomes.

Publications

Comparative analysis of processed ribosomal protein pseudogenes in four mammalian genomes.

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