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 5Ј end than the 3Ј 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.All of the proteins in the cell are synthesized by the ribosomes, large complexes of RNA and protein molecules. A typical mammalian cell has about 4 ‫ן‬ 10 6 ribosomes, and each is composed of four RNA molecules (rRNA) and 79 ribosomal proteins (RPs). In total, ribosomes constitute about 80% of the RNA and 5%-10% of the protein in a cell (Kenmochi et al. 1998). Great progress has been made in recent years in elucidating the structure and mechanism of the ribosome. The peptide sequence of the complete set of mammalian RPs was deduced by Wool and colleagues (1995), and the genes encoding all human RPs have been positioned on the human genetic map (Kenmochi et al. 1998;Uechi et al. 2001;Yoshihama et al. 2002). Moreover, several high-resolution atomic structures are now available for archaeal ribosomes (Ban et al. 2000;Schluenzen et al. 2000;Wimberly et al. 2000;Yu...

Evaluation of candidate control genes for diagnosis and residual disease detection in leukemic patients using ‘real-time’ quantitative reverse-transcriptase polymerase chain reaction (RQ-PCR) – a Europe against cancer program

“…Among the four highly expressed CGs (acidic ribosomal PO protein gene (PO, ACTB, GAPD, and B2M), only B2M was not known to have pseudogenes. 15,31,32 However, B2M expression analyzed by the ABI set differed significantly between normal and leukemic samples and between PB and BM (Po0.001 in both cases, n ¼ 65, Mann-Whitney test). Therefore, the ABI B2M set was discarded.…”

“…13,14 Furthermore, the selected gene should not present any pseudogenes, in order to avoid any genomic DNA amplification. 14,15 An impaired amplification of CGs should be accompanied by a corresponding reduction in the quantity of target gene transcript(s). Variation in amplification would reflect variations in RNA quality, quantity and/or cDNA synthesis efficiency.…”

Identification and bioinformatics analysis of pseudogenes from whole genome sequence of Phaeodactylum tricornutum

“…It has been suggested that, over time, the remaining poly(A) fragments in the processed pseudogenes will slowly degrade or even disappear [33,34]. Thus, some of the pseudogenes in chromosome 13 of P. tricornutum might have emerged later than the pseudogenes in other chromosomes.…”

“…When the overlap of adjacent sequences was over 30 bp, the sequences were arranged in descending order according to their importance (the higher the E-value the lower their importance) and matching objects of low importance were removed. Sequences fulfilling the following three criteria were considered as the same candidate pseudogene (a) |q21-q12| ≤ max (20, 0.2L), (b) c21-c12 ≤ 3000, and (c) c22-c21≤ 60 (these parameters are the same as those that were defined previously [33]). The longest P. tricornutum intron was 9880 bp and the shortest was 20 bp.…”

“…Schematic graph showing the considerations used in merging two adjacent matches M1 and M2. (c11, c12) and (c21, c22) are chromosomal coordinates for M1 and M2; (q11, q12) and (q21, q22) are the corresponding matching regions on the query functional protein [33].…”