Human Ribosomal RNA Genes

 
Humans 5S RNA genes are about 200 bp in size from the transcription start site to the termination site. The precursor is processed to give the mature 120 bp 5S RNA that is incorporated into ribosomes [Ribosomal RNA Genes in Eukaryotes].

5S RNA genes are arranged as tandem repeats in a large cluster on chromosome 1 (1q42). The number of repeats varies from individual to individual within the range of 35-175 copies (Stults et al. 2008). The length of the repeats also varies but most of the genes are part of a 2200 bp repeat. Since only a small part of this is actually transcribed (200 bp) it looks like much of this locus is non-essential DNA. (The 5S RNA repeat in macaques is 7300 bp and in rats it is 1800 bp.)

The reported human genome sequences do not contain the region of the 5S RNA genes. It is impossible to clone and assemble fragments of repeated DNA sequences.


The other ribosomal RNA genes are located in a single transcription unit that gives rise to an RNA precursor of 13,000 bp. This is known as 45 RNA and the "gene" (operon) is often called the 45S gene. This large transcript is processed to give three mature RNAs: 18S (1874 bp), 5.8S (160 bp), and 28S (4718 bp) [Ribosomal RNA Genes in Eukaryotes].

The transcription units are arranged mostly as head-to-tail tandem repeats of 43 kb. Thus, 30 kB of this repeat unit consists of non-transcribed spacer. The length of this non-transcribed spacer varies from species to species although it tends to be the same within a given species (but see below). The conservation of length and sequence in a region of DNA that is non-essential may seem surprising but it is related to the frequent recombination events that occur at the sites of ribosomal RNA genes. The genes themselves are almost identical in sequence as a result of concerted evolution or gene conversion. The flanking regions (non-transccribed spacers) are "conserved" because they are carried along.

Let's assume that 20 kb of the non-transcribed spacer is non-functional and non-essential (= junk). That means 23 kb (13 kb of 45S transcript and 10 kb of spacer) is essential for proper function of the ribosomal RNA genes.



The ribosomal RNA genes are located at regions called nucleolar organizer regions (NORs) because this is the site where a nucleolus forms within the nucleus. The nucleolus is actually a dense region of the nucleus where massive transcripton of ribosomal RNA genes is occurring.

In humans, there are five clusters of ribosomal RNA genes (NORs) located at 13p12, 14p12, 15p12, 21p12, and 22p12. All of them are found in distinctive regions at the ends of apocentric chromosomes (chromosomes with a centromere region near one end). Cluster lengths (number of repeats) varies from individual to individual. The frequency of recombination events leading to rearrangements is ~10% per generation. This means that almost every individual has a unique fingerprint of ribosomal RNA gene repeats. (Each of us has 10 clusters.)

There are about 600 repeats in the average diploid genome (Stults, 2008). (This means 300 repeats in the haploid genome.) As is the case with the 5S repeats, none of the nucleolar organizer regions has been cloned and sequenced. All five loci are represented by large gaps in the "finished" genome.

The total amount of DNA in the large ribosomal RNA clusters is 12,900 kb (300 × 43 kb). Of this amount 6,000 kb (47 %) is probably junk in the sense that it is dispensible.

Junk in Your Genome

Ribosomal RNA Genes

Total DNA = 13,120 kb (0.41%)

Essential = 7,000 kb (0.22%)

Junk = 6,120 kb (0.19%)

Many of the human 45S genes are pseudogenes and unusual rearrangements are common (Caburet et al., 2005). In mouse, up to half of all the 45S genes are non-functional pseudogenes. Presumably these are due to errors in recombination events and they are likely to be transient.

The minimum number of 45S genes in mammals is not known for certain in humans but in chickens the loss of anything more than half the average number is lethal. It seems reasonable that of the 300 or so human 45S genes only about 150 are absolutely required and the remainder are dispensable. However, concerted evolution of these genes is essential in the long run and the mechanism of concerted evolution and gene conversion requires lots of copies. Thus, all copies are necessary for the species even though only half may be required for any one individual.

Total ribosomal RNA genes in the genome:

5S: 100 copies of 2.2 kb repeats = 220 kb. (estimate 100 kb essential, 120 kb junk)
45S: 300 copies of 43 kb repeats = 12,900 kb. (estimate 7,000 kb essential, 6,120 junk)

UPDATED: May 10, 2011

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Caburet, S., Conti, C., Schurra, C., Lebofsky, R., Edelstein, S.J. and Bensimon, A. (2005) Human ribosomal RNA gene arrays display a broad range of palindromic structures. Genome Res. 15:1079-85. [PubMed]

Stults, D.M., Killen, M.W., Pierce, H.H. and Pierce, A.J. (2008) Genomic architecture and inheritance of human ribosomal RNA gene clusters. Genome Res. 18:13-18. [PubMed] [Genome Research]