Characteristics and clustering of human ribosomal protein genes

Abstract

Background: The ribosome is a central player in the translation system, which in mammals consists of four RNA species and 79 ribosomal proteins (RPs). The control mechanisms of gene expression and the functions of RPs are believed to be identical. Most RP genes have common promoters and were therefore assumed to have a unified gene expression control mechanism.

Results: We systematically analyzed the homogeneity and heterogeneity of RP genes on the basis of their expression profiles, promoter structures, encoded amino acid compositions, and codon compositions. The results revealed that (1) most RP genes are coordinately expressed at the mRNA level, with higher signals in the spleen, lymph node dissection (LND), and fetal brain. However, 17 genes, including the P protein genes (RPLP0, RPLP1, RPLP2), are expressed in a tissue-specific manner. (2) Most promoters have GC boxes and possible binding sites for nuclear respiratory factor 2, Yin and Yang 1, and/or activator protein 1. However, they do not have canonical TATA boxes. (3) Analysis of the amino acid composition of the encoded proteins indicated a high lysine and arginine content. (4) The major RP genes exhibit a characteristic synonymous codon composition with high rates of G or C in the third-codon position and a high content of AAG, CAG, ATC, GAG, CAC, and CTG.

Conclusion: Eleven of the RP genes are still identified as being unique and did not exhibit at least some of the above characteristics, indicating that they may have unknown functions not present in other RP genes. Furthermore, we found sequences conserved between human and mouse genes around the transcription start sites and in the intronic regions. This study suggests certain overall trends and characteristic features of human RP genes.

Figure 1

Expression profiles of human ribosomal protein (RP) genes in 30 tissues. (A) Hierarchical clustering of tissue expression profile using a centroid linkage algorithm. Black regions represent low gene expression level for that gene (row) in the tissue (column), whereas the red regions represent high gene expression level. The genes in the Main cluster, Sub-cluster 1, and Sub-cluster 2 show a correlation coefficient value of 0.94, 0.98 and 0.75, respectively.(B) Detection of differentially expressed RP genes by Grubbs' outlier test. Red regions represent genes (row) expressed at significantly higher rates in a certain tissue (column) than any other RP gene. Blue regions represent genes expressed at significantly lower rates than any other RP gene. A P value <0.05 was considered significant.

Figure 2

Transcription factor binding sites predicted by phylogenetic footprinting. The distance from the TSS (bp) is shown on the X axis, and the identity (%) with the orthologous mouse gene is shown on the Y axis. Black boxes indicate exons. Each thin line represents a location of a predicted promoter (NRF: nuclear respiratory factor 2; YY: Yin and Yang 1; GC: GC boxes; AP: activator protein 1; TA: TATA boxes).

Figure 3

Distribution of predicted transcription factor binding sites. The distance from the TSS (bp) is shown on the X axis, and the number of predicted transcription factor binding sites is shown on the Y axis. The red triangle depicts TSS (+1).

Figure 4

Hierarchical clustering of ribosomal protein (RP) genes by amino acid composition. The black regions represent low frequencies of encoding of the amino acid (column) by that gene (row) whereas the red regions represent high frequencies of encoding. (F: Phenylalanine, L: Leucine, I: Isoleucine, M: Methionine, V: Valine, P: Proline, T: Threonine, A: Alanine, Y: Tyrosine, H: Histidine, Q: Glutamine, N: Asparagine, K: Lysine, D: Aspartic acid, E: Glutamic acid, C: Cysteine, W: Tryptophan, R: Arginine, S: Serine, G: Glycine)

Figure 5

Hierarchical clustering of synonymous codon composition. The black regions represent low rates of occurrence of the codon (column) in that gene (row), whereas the red regions represent high rates of occurrence.