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Review
. 2021 Jan 20;10(2):196.
doi: 10.3390/cells10020196.

Variability of Human rDNA

Evgeny Smirnov  1 , Nikola Chmúrčiaková  1 , František Liška  1 , Pavla Bažantová  1 , Dušan Cmarko  1
Affiliations
Review

Variability of Human rDNA

Evgeny Smirnov et al. Cells. .

Abstract

In human cells, ribosomal DNA (rDNA) is arranged in ten clusters of multiple tandem repeats. Each repeat is usually described as consisting of two parts: the 13 kb long ribosomal part, containing three genes coding for 18S, 5.8S and 28S RNAs of the ribosomal particles, and the 30 kb long intergenic spacer (IGS). However, this standard scheme is, amazingly, often altered as a result of the peculiar instability of the locus, so that the sequence of each repeat and the number of the repeats in each cluster are highly variable. In the present review, we discuss the causes and types of human rDNA instability, the methods of its detection, its distribution within the locus, the ways in which it is prevented or reversed, and its biological significance. The data of the literature suggest that the variability of the rDNA is not only a potential cause of pathology, but also an important, though still poorly understood, aspect of the normal cell physiology.

Keywords: copy number; human rDNA; mutations; sequence variability.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Distribution of the variability among the regions of human rDNA unit. (A) Standard structure of the rDNA cluster. (B) Individual rDNA unit. The unit consists of the ~13 kb long ribosomal part and ~30 kb long IGS. The ribosomal part includes three genes: 18S, 5.8S, and 28S, coding for the respective rRNAs; p—promoter; sp—spacer promoter; two external spacers: 5′ETS and 3′ETS; two internal spacers: ITS1 and ITS2. Restriction site HincII in the 28S region is marked by arrowhead. LR1 and LR2 represent two large repeats, and each of them contains two Alu sequences. (C) Thermogram showing relative abundance of variants and breakpoints in various regions of the unit. The least variable are two genes and a region including core and upstream control elements of the promoter. The most variable are both LRs and a part of 28S gene containing HincII site.
Figure 2
Figure 2
Large-scale variability of human rDNA. (A) The standard structure, in which promoter (red) is followed by ~13 kb long ribosomal region (green) and ~30 kb long IGS (blue). This pattern does not seem to be very frequent, but it is preserved in the cell generations. (B) Five 3′-3′ palindromes arranged in a cluster. (C) one normal unit followed by five 5′-5′ palindromes arranged in a cluster. (D) Units with variable length of ribosomal part and IGS. (E) Inversion involving six units. The last unit at the right has standard orientation. Arrowheads indicate deleted promoters.
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