Repeated sequences (also known as repetitive elements, repeating units or repeats) are short or long patterns that occur in multiple copies throughout the genome. In many organisms, a significant fraction of the genomic DNA is repetitive, with over two-thirds of the sequence consisting of repetitive elements in humans. Some of these repeated sequences are necessary for maintaining important genome structures such as telomeres or centromeres. Repeated sequences are categorized into different classes depending on features such as structure, length, location, origin, and mode of multiplication. The disposition of repetitive elements throughout the genome can consist either in directly adjacent arrays called tandem repeats or in repeats dispersed throughout the genome called interspersed repeats. Tandem repeats and interspersed repeats are further categorized into subclasses based on the length of the repeated sequence and/or the mode of multiplication. While some repeated DNA sequences are important for cellular functioning and genome maintenance, other repetitive sequences can be harmful. Many repetitive DNA sequences have been linked to human diseases such as Huntington's disease and Friedreich's ataxia. Some repetitive elements are neutral and occur when there is an absence of selection for specific sequences depending on how transposition or crossing over occurs. However, an abundance of neutral repeats can still influence genome evolution as they accumulate over time. Overall, repeated sequences are an important area of focus because they can provide insight into human diseases and genome evolution.
History In the 1950s, Barbara McClintock first observed DNA transposition and illustrated the functions of the centromere and telomere at the Cold Spring Harbor Symposium. McClintock's work set the stage for the discovery of repeated sequences because transposition, centromere structure, and telomere structure are all possible through repetitive elements, yet this was not fully understood at the time. The term "repeated sequence" was first used by Roy John Britten and D. E. Kohne in 1968; they found out that more than half of the eukaryotic genomes were repetitive DNA through their experiments on reassociation of DNA. Although the repetitive DNA sequences were conserved and ubiquitous, their biological role was yet unknown. In the 1990s, more research was conducted to elucidate the evolutionary dynamics of minisatellite and microsatellite repeats because of their importance in DNA-based forensics and molecular ecology. DNA-dispersed repeats were increasingly recognized as a potential source of genetic variation and regulation. Discoveries of deleterious repetitive DNA-related diseases stimulated further interest in this area of study. In the 2000s, the data from full eukaryotic genome sequencing enabled the identification of different promoters, enhancers, and regulatory RNAs which are all coded by repetitive regions. Today, the structural and regulatory roles of repetitive DNA sequences remain an active area of research.
Types and functions Many repeat sequences are likely to be non-functional, decaying remnants of Transposable elements, these have been labelled "junk" or "selfish" DNA. Nevertheless, occasionally some repeats may be exapted for other functions.
Tandem repeats Tandem repeats are repeated sequences which are directly adjacent to each other in the genome. Tandem repeats may vary in the number of nucleotides comprising the repeated sequence, as well as the number of times the sequence repeats. When the repeating sequence is only 2–10 nucleotides long, the repeat is referred to as a short tandem repeat (STR) or microsatellite. When the repeating sequence is 10–60 nucleotides long, the repeat is referred to as a minisatellite. For minisatellites and microsatellites, the number of times the sequence repeats at a single locus can range from twice to hundreds of times. Tandem repeats have a wide variety of biological functions in the genome. For example, minisatellites are often hotspots of meiotic homologous recombination in eukaryotic organisms. Recombination is when two homologous chromosomes align, break, and rejoin to swap pieces. Recombination is important as a source of genetic diversity, as a mechanism for repairing damaged DNA, and a necessary step in the appropriate segregation of chromosomes in meiosis. The presence of repeated sequence DNA makes it easier for areas of homology to align, thereby controlling when and where recombination occurs. In addition to playing an important role in recombination, tandem repeats also play important structural roles in the genome. For example, telomeres are composed mainly of tandem TTAGGG repeats. These repeats fold into highly organized G quadruplex structures which protect the ends of chromosomal DNA from degradation. Repetitive elements are enriched in the middle of chromosomes as well. Centromeres are the highly compact regions of chromosomes which join sister chromatids together and also allow the mitotic spindle to attach and separate sister chromatids during cell division. Centromeres are composed of a 177 base pair tandem repeat named the α-satellite repeat. Pericentromeric heterochromatin, the DNA which surrounds the centromere and is important for structural maintenance, is composed of a mixture of different satellite subfamilies including the α-, β- and γ-satellites as well as HSATII, HSATIII, and sn5 repeats.
Some repetitive sequences, such as those with structural roles discussed above, play roles necessary for proper biological functioning. Other tandem repeats have deleterious roles which drive diseases. Many other tandem repeats, however, have unknown or poorly understood functions.
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