The human ribosomal protein genes: sequencing and comparative analysis of 73 genes

Abstract

The ribosome, as a catalyst for protein synthesis, is universal and essential for all organisms. Here we describe the structure of the genes encoding human ribosomal proteins (RPs) and compare this class of genes among several eukaryotes. Using genomic and full-length cDNA sequences, we characterized 73 RP genes and found that (1) transcription starts at a C residue within a characteristic oligopyrimidine tract; (2) the promoter region is GC rich, but often has a TATA box or similar sequence element; (3) the genes are small (4.4 kb), but have as many as 5.6 exons on average; (4) the initiator ATG is in the first or second exon and is within plus minus 5 bp of the first intron boundaries in about half of cases; and (5) 5'- and 3'-UTRs are significantly smaller (42 bp and 56 bp, respectively) than the genome average. Comparison of RP genes from humans, Drosophila melanogaster, Caenorhabditis elegans, and Saccharomyces cerevisiae revealed the coding sequences to be highly conserved (63% homology on average), although gene size and the number of exons vary. The positions of the introns are also conserved among these species as follows: 44% of human introns are present at the same position in either D. melanogaster or C. elegans, suggesting RP genes are highly suitable for studying the evolution of introns.

Figure 1

Schematic representation of RP gene organization. Solid boxes indicate exons. Arrowheads show the position corresponding to the translation start and stop sites. Red circles represent the position of the snoRNA genes.

Figure 2

Distribution of RP gene features. Shown are size distributions of genes and CDSs (A), exons (B) and 5′-and 3′-UTRs (C), as well as the numbers of exons (D).

Figure 3

Characteristics of the promoter regions. Features including oligopyrimidine tracts (green), TATA boxes (pink), TATA-like sequences (yellow), and possible binding sites for Ets proteins (blue) are indicated. Arrowheads represent the position of the transcription start site. Upper- and lowercase letters denote exon and intron sequences, respectively.

Figure 4

Features of the oligopyrimidine tract. (A) Size distribution: Min, 5 bp; Max, 25 bp; Mean, 11.6 bp. (B) Position of the transcription start site within a oligopyrimidine tract; Mean, 4.0.

Figure 5

Variation of the transcription start sites. Three types of variations are detected: (1) transcription starts at a different C (or T) residue within an oligopyrimidine tract (e.g., RPL32); (2) transcription starts at a C residue in distinct oligopyrimidine tracts (e.g., RPL39); and (3) transcription start at the same C residue but the length of the T stretches vary (e.g., RPS20). These variations will appear in the DDBJ/EMBL/GenBank DNA database under accession nos. D28385, D28397, and D28358 (for a complete list, see Table 1). Arrowheads indicate the possible transcription start sites. T-stretches of variable length are shaded.

Figure 6

Comparison of intron positions among human, fruitfly (D. melanogaster), nematode worm (C. elegans), and yeast (S. cerevisiae) RP genes. Intron positions for 60 genes were compared. 'Unique' represents the ratio of introns that are specific to that particular species. The number of analyzed introns was 249 in Human, 97 in Fly, 123 in Worm, and 67 in Yeast.

Figure 7

Comparison of the intron/exon structures and the CDS homology of RPL8. (A) Yellow and red lines indicate the corresponding positions of the human splice sites with those in other species. Yeast has two copies of the RPL8 gene, designated as Yeast-A and Yeast-B. Solid boxes represent exons, and arrowheads represent the position corresponding to the translation start and stop. (B) CDS homology of RPL8 between any two of the four species.