Comparative analysis of processed ribosomal protein pseudogenes in four mammalian genomes

Abstract

Background: 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.

Results: 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.

Conclusions: 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.

Figure 1

Plot of expression level of mRNA in testes associated with each RP protein versus the number of processed pseudogenes associated with it. The top and bottom panels correspond to human and mouse RP pseudogenes, respectively. The x-axis shows signal on the gene chip, which is a measure of the abundance of a mRNA transcript. Data for the human and mouse are not normalized to each other and should not be compared directly. It should be noted that expression data for some RP proteins for mouse are missing in the GEO data.

Figure 2

Plots depicting the number of processed pseudogenes associated with a RP protein in one organism and its corresponding ortholog in another organism. The top panel shows the comparison between human versus mouse and the bottom panel depicts the same for mouse versus rat RP pseudogenes. Each point corresponds to the number of processed RP pseudogenes associated with one RP in the two species that are being compared.

Figure 3

Schematic representation of the method used to identify syntenic regions between two species. In this figure, the pseudogenes are depicted as yellow boxes and human genes that have orthologs in mouse have been labeled. As explained in the text, the human gene SPRY1 and Y1223_HUMAN sandwich the processed RP pseudogene of RPL21 and have corresponding orthologs in the mouse genome. Thus, we identify this region as being syntenic between human and mouse. Orthologs were identified based on annotations from Ensembl release 36.

Figure 4

Processed pseudogenes grouped according to their nucleotide sequence divergence from the parent RP protein. The distances have been calculated using MEGA [28]. The distance is a measure of the number of nucleotide substitutions per site. For mouse and rat, the distances have been scaled by decreasing it by a factor of three based on the reported observation that a threefold-higher rate of base substitution in neutral DNA is found along the rodent lineage when compared with the human lineage [20].