Inverted repeat

Example of an inverted repeat Beginning with this initial sequence:             The complement created by base pairing is:             The reverse complement is:             And, the inverted repeat sequence is:             "nnnnnn" represents any number of intervening nucleotides. Vs. direct repeat A direct repeat occurs when a sequence is repeated with the same pattern downstream. There is no inversion and no reverse complement associated with a direct repeat. The nucleotide sequence written in bold characters signifies the repeated sequence. It may or may not have intervening nucleotides. ::: ::: Linguistically, a typical direct repeat is comparable to rhyming, as in "time on a dime". Vs. tandem repeat A direct repeat with no intervening nucleotides between the initial sequence and its downstream copy is a Tandem repeat. The nucleotide sequence written in bold characters signifies the repeated sequence. ::: ::: Linguistically, a typical tandem repeat is comparable to stuttering, or deliberately repeated words, as in "bye-bye". Vs. palindrome An inverted repeat sequence with no intervening nucleotides between the initial sequence and its downstream reverse complement is a palindrome.     EXAMPLE:         Step 1: start with an inverted repeat:         Step 2: remove intervening nucleotides:         This resulting sequence is palindromic because it is the reverse complement of itself. :::   test sequence (from Step 2 with intervening nucleotides removed) :::   complement of test sequence :::   reverse complement     This is the same as the test sequence above, and thus, it is a palindrome. ==Biological features and functionality==

Conditions that favor synthesis The diverse genome-wide repeats are derived from transposable elements, which are now understood to "jump" about different genomic locations, without transferring their original copies. Subsequent shuttling of the same sequences over numerous generations ensures their multiplicity throughout the genome. Regions where presence is obligatory Terminal inverted repeats have been observed in the DNA of various eukaryotic transposons, even though their source remains unknown. Inverted repeats are principally found at the origins of replication of cell organism and organelles that range from phage plasmids, mitochondria, and eukaryotic viruses to mammalian cells. The replication origins of the phage G4 and other related phages comprise a segment of nearly 139 nucleotide bases that include three inverted repeats that are essential for replication priming. Other reports suggest that irrespective of the comparative shortage of repeat elements in prokaryotic genomes, they nevertheless contain hundreds or even thousands of large repeats. Current genomic analysis seem to suggest the existence of a large excess of perfect inverted repeats in many prokaryotic genomes as compared to eukaryotic genomes. For quantification and comparison of inverted repeats between several species, namely on archaea, see Inverted repeats in pseudoknots Pseudoknots are common structural motifs found in RNA. They are formed by two nested stem-loops such that the stem of one structure is formed from the loop of the other. There are multiple folding topologies among pseudoknots and great variation in loop lengths, making them a structurally diverse group. Inverted repeats are a key component of pseudoknots as can be seen in the illustration of a naturally occurring pseudoknot found in the human telomerase RNA component. Four different sets of inverted repeats are involved in this structure. Sets 1 and 2 are the stem of stem-loop A and are part of the loop for stem-loop B. Similarly, sets 3 and 4 are the stem for stem-loop B and are part of the loop for stem-loop A. Pseudoknots play a number of different roles in biology. The telomerase pseudoknot in the illustration is critical to that enzyme's activity. The stem-loop on the 3' end is a transcriptional terminator because the sequence immediately following it is a string of uracils (U). If this stem-loop forms (due to the presence of FMN) as the growing RNA strand emerges from the RNA polymerase complex, it will create enough structural tension to cause the RNA strand to dissociate and thus terminate transcription. The dissociation occurs easily because the base-pairing between the U's in the RNA and the A's in the template strand are the weakest of all base-pairings. Thus, at higher concentration levels, FMN down-regulates its own transcription by increasing the formation of the termination structure. ==Mutations and disease==

Inverted repeats are often described as "hotspots" of eukaryotic and prokaryotic genomic instability. Long inverted repeats are deemed to greatly influence the stability of the genome of various organisms. This is exemplified in E. coli, where genomic sequences with long inverted repeats are seldom replicated, but rather deleted with rapidity. The illustration shows an inverted repeat undergoing cruciform extrusion. DNA in the region of the inverted repeat unwinds and then recombines, forming a four-way junction with two stem-loop structures. The cruciform structure occurs because the inverted repeat sequences self-pair to each other on their own strand. Extruded cruciforms can lead to frameshift mutations when a DNA sequence has inverted repeats in the form of a palindrome combined with regions of direct repeats on either side. During transcription, slippage and partial dissociation of the polymerase from the template strand can lead to both deletion and insertion mutations. Deletion occurs when a portion of the unwound template strand forms a stem-loop that gets "skipped" by the transcription machinery. Insertion occurs when a stem-loop forms in a dissociated portion of the nascent (newly synthesized) strand causing a portion of the template strand to be transcribed twice. Antithrombin deficiency from a point mutation Imperfect inverted repeats can lead to mutations through intrastrand and interstrand switching. The antithrombin III gene's coding region is an example of an imperfect inverted repeat as shown in the figure on the right. The stem-loop structure forms with a bump at the bottom because the G and T do not pair up. A strand switch event could result in the G (in the bump) being replaced by an A which removes the "imperfection" in the inverted repeat and provides a stronger stem-loop structure. However, the replacement also creates a point mutation converting the GCA codon to ACA. If the strand switch event is followed by a second round of DNA replication, the mutation may become fixed in the genome and lead to disease. Specifically, the missense mutation would lead to a defective gene and a deficiency in antithrombin which could result in the development of venous thromboembolism (blood clots within a vein). Osteogenesis imperfecta from a frameshift mutation Mutations in the collagen gene can lead to the disease Osteogenesis Imperfecta, which is characterized by brittle bones. In the illustration, a stem-loop formed from an imperfect inverted repeat is mutated with a thymine (T) nucleotide insertion as a result of an inter- or intrastrand switch. The addition of the T creates a base-pairing "match up" with the adenine (A) that was previously a "bump" on the left side of the stem. While this addition makes the stem stronger and perfects the inverted repeat, it also creates a frameshift mutation in the nucleotide sequence which alters the reading frame and will result in an incorrect expression of the gene. ==Programs and databases==

The following list provides information and external links to various programs and databases for inverted repeats: • non-B DB A Database for Integrated Annotations and Analysis of non-B DNA Forming Motifs. This database is provided by The Advanced Biomedical Computing Center (ABCC) at then Frederick National Laboratory for Cancer Research (FNLCR). It covers the A-DNA and Z-DNA conformations otherwise known as "non-B DNAs" because they are not the more common B-DNA form of a right-handed Watson-Crick double-helix. These "non-B DNAs" include left-handed Z-DNA, cruciform, triplex, tetraplex and hairpin structures. • P-MITE: a Plant MITE database — this database for Miniature Inverted-repeat Transposable Elements (MITEs) contains sequences from plant genomes. Sequences may be searched or downloaded from the database. • EMBOSS is the "European Molecular Biology Open Software Suite" which runs on UNIX and UNIX-like operating systems. Documentation and program source files are available on the EMBOSS website. Applications specifically related to inverted repeats are listed below: • EMBOSS einverted: Finds inverted repeats in nucleotide sequences. Threshold values can be set to limit the scope of the search. • EMBOSS palindrome: Finds palindromes such as stem loop regions in nucleotide sequences. The program will find sequences that include sections of mismatches and gaps that may correspond to bulges in a stem loop. ==References==