Finely orchestrated movements: evolution of the ribosomal RNA genes

Abstract

Evolution of the tandemly repeated ribosomal RNA (rRNA) genes is intriguing because in each species all units within the array are highly uniform in sequence but that sequence differs between species. In this review we summarize the origins of the current models to explain this process of concerted evolution, emphasizing early studies of recombination in yeast and more recent studies in Drosophila and mammalian systems. These studies suggest that unequal crossover is the major driving force in the evolution of the rRNA genes with sister chromatid exchange occurring more often than exchange between homologs. Gene conversion is also believed to play a role; however, direct evidence for its involvement has not been obtained. Remarkably, concerted evolution is so well orchestrated that even transposable elements that insert into a large fraction of the rRNA genes appear to have little effect on the process. Finally, we summarize data that suggest that recombination in the rDNA locus of higher eukaryotes is sufficiently frequent to monitor changes within a few generations.

Figure 1.—

Organization of the ribosomal RNA (rRNA) genes in eukaryotes. The genes are organized into tandemly repeated units as diagrammed at the top. A typical unit is shown in expanded detail. The positions of the three rRNA genes (18S, 5.8S, 28S) are indicated with solid boxes, while regions processed from the primary transcript are in open boxes (ETS, external transcribed spacer; ITS, internal transcribed spacer). Between the transcription units are the intergenic spacers (IGS), which in most species are composed of one or more internally repeated sequences (shaded arrowheads). The extent and direction of the transcribed region of each unit as well as the final mature rRNAs derived from that transcript are shown at the bottom as dotted arrows.

Figure 2.—

Four possible recombination mechanisms that may occur within or between rDNA loci. A and A′ represent homologous chromosomes; the rectangles, individual rDNA units; and the small solid boxes, mutations. Each chromosome is drawn after replication to show the two sister chromatids still attached by means of their centromeres (solid oval). All four recombination mechanisms can lead to the duplication or loss of a mutation on a chromosome. The three crossover events (A, B, and C) can lead to changes in the number of rDNA units on a chromosome, while gene conversion (D) will not unless a crossover also occurs.

Figure 3.—

Location of the rDNA loci on the chromosomes of humans and mice. Each chromosome is drawn after replication to show the two sister chromatids still attached by means of their centromeres (solid oval). Individual rDNA units are indicated by rectangles and the telomeres by triangles. Each chromosome is representative of the multiple nonhomologous chromosomes that contain the rDNA units in each species. The noncoding region distal to the rDNA loci in humans studied by Gonzalez and Sylvester (2001) is indicated (asterisk).

Figure 4.—

Location of mobile element insertions in the rDNA unit. Abbreviations within the rDNA transcription unit are as described in Figure 1. A small region of the 28S gene, which contains many insertion classes, is magnified above this repeat. Arrows indicate the insertion site of the various elements based on their 3′ junction with the gene. The current known distribution of each element is also shown. For more detailed descriptions of these elements see Eickbush (2002), Kojima and Fujiwara (2003), and Kojima et al. (2006).