Comparative Genomics and Molecular Dynamics of DNA Repeats in Eukaryotes

Abstract

SUMMARY Repeated elements can be widely abundant in eukaryotic genomes, composing more than 50% of the human genome, for example. It is possible to classify repeated sequences into two large families, “tandem repeats” and “dispersed repeats.” Each of these two families can be itself divided into subfamilies. Dispersed repeats contain transposons, tRNA genes, and gene paralogues, whereas tandem repeats contain gene tandems, ribosomal DNA repeat arrays, and satellite DNA, itself subdivided into satellites, minisatellites, and microsatellites. Remarkably, the molecular mechanisms that create and propagate dispersed and tandem repeats are specific to each class and usually do not overlap. In the present review, we have chosen in the first section to describe the nature and distribution of dispersed and tandem repeats in eukaryotic genomes in the light of complete (or nearly complete) available genome sequences. In the second part, we focus on the molecular mechanisms responsible for the fast evolution of two specific classes of tandem repeats: minisatellites and microsatellites. Given that a growing number of human neurological disorders involve the expansion of a particular class of microsatellites, called trinucleotide repeats, a large part of the recent experimental work on microsatellites has focused on these particular repeats, and thus we also review the current knowledge in this area. Finally, we propose a unified definition for mini- and microsatellites that takes into account their biological properties and try to point out new directions that should be explored in a near future on our road to understanding the genetics of repeated sequences.

Structures and functions in the crowded nucleus: new biophysical insights

“…Nevertheless, irregular conformations were seen quite commonly in vivo in studies by electron and optical microscopy (for example [31,32]) ( Figure 3B) and were also predicted by simulation of the response to crowding of linear polyelectrolyte polymers [9,33] (Figure 3A) and by considering that chromosomes resemble block copolymers [34,35] with interspersed regions of repeated DNA sequences [36], methylated cytosine-containing DNA which has particular conformational properties [37,38], and nucleosomes containing variant or modified histones which influence fiber interactions [39,40]. These discrepancies have been resolved by recent cryo-electron microscopy and X-ray scattering studies, which show conclusively that chromatin fibers exist in vivo in a disordered, interdigitated state resembling a polymer melt [41].…”

DNA tandem repeat instability in the Escherichia coli chromosome is stimulated by mismatch repair at an adjacent CAG·CTG trinucleotide repeat

“…DNA repair | DNA replication | fragile site R epetitive DNA is a prominent characteristic of many eukaryotic genomes including that of humans (1). This complexity of DNA sequence carries with it a danger of genome rearrangement as repetitive sequences are sites where recombination or replication slippage events can occur.…”

Regulation of ribosomal DNA amplification by the TOR pathway

“…Our results reveal how a signaling pathway can orchestrate specific genome changes and demonstrate that the copy number of repetitive DNA can be altered to suit environmental conditions. ribosomal DNA | homologous recombination | Sir2 | copy number variation | TOR E ukaryotic genomes contain abundant multicopy sequences, ranging from low copy segmental duplications to the giant tandem arrays found at key functional regions such as centromeres, telomeres, and the ribosomal DNA (rDNA) (1). Copy number variation of protein coding genes has been linked with multiple diseases, suggesting copy number has significant effects on gene expression (2,3).…”