Repeated sequences (also known as repetitive elements, repeating units or repeats) are patterns of nucleic acids (DNA or RNA) that occur in multiple copies throughout the genome. Repetitive DNA was first detected because of its rapid re-association kinetics. In many organisms, a significant fraction of the genomic DNA is highly repetitive, with over two-thirds of the sequence consisting of repetitive elements in humans.
Repetitive elements found in genomes fall into different classes, depending on their structure and/or the mode of multiplication. The disposition of repetitive elements consists either in arrays of tandemly repeated sequences, or in repeats dispersed throughout the genome (see below).
Debates regarding the potential functions of these elements have been long standing. Controversial references to ‘junk’ or ‘selfish’ DNA were put forward early on, implying that repetitive DNA segments are remainders from past evolution or autonomous self-replicating sequences hacking the cell machinery to proliferate. Originally discovered by Barbara McClintock, dispersed repeats have been increasingly recognized as a potential source of genetic variation and regulation. Together with these regulatory roles, a structural role of repeated DNA in shaping the 3D folding of genomes has also been proposed. This hypothesis is only supported by a limited set of experimental evidence. For instance in human, mouse and fly, several classes of repetitive elements present a high tendency for co-localization within the nuclear space, suggesting that DNA repeats positions can be used by the cell as a genome folding map.
Tandem repeat sequences, particularly trinucleotide repeats, underlie several human disease conditions. Trinucleotide repeats may expand in the germline over successive generations leading to increasingly severe manifestations of the disease. The disease conditions in which expansion occurs include Huntington’s disease, fragile X syndrome, several spinocerebellar ataxias, myotonic dystrophy and Friedrich ataxia. Trinucleotide repeat expansions may occur through strand slippage during DNA replication or during DNA repair synthesis.
Hexanucleotide GGGGCC repeat sequences in the C9orf72 gene are a common cause of amyotrophic lateral sclerosis and frontotemporal dementia. CAG trinucleotide repeat sequences underlie several spinocerebellar ataxias (SCAs-SCA1; SCA2; SCA3; SCA6; SCA7; SCA12; SCA17). Huntington’s disease results from an unstable expansion of repeated CAG sequences in exon 1 of the huntingtin gene (HTT). HTT encodes a scaffold protein that directly participates in repair of oxidative DNA damage. It has been noted that genes containing pathogenic CAG repeats often encode proteins that themselves have a role in the DNA damage response and that repeat expansions may impair specific DNA repair pathways. Faulty repair of DNA damages in repeat sequences may cause further expansion of these sequences, thus setting up a vicious cycle of pathology.
Major categories of repeated sequence or repeats:
In primates, the majority of LINEs are LINE-1 and the majority of SINEs are Alu's. SVAs are hominoid specific.
In prokaryotes, CRISPR are arrays of alternating repeats and spacers.
Repeated sequences evolutionary derived from viral infection events.
Note: The following are covered in detail in "Computing for Comparative Microbial Genomics".
Repetitive DNA is hard to sequence using next-generation sequencing techniques: sequence assembly from short reads simply cannot determine the length of a repetitive part. This issue is particularly serious for microsatellites, which are made of tiny 1-6bp repeat units.
Many researchers have historically left out repetitive parts when analyzing and publishing whole genome data.