Glossary

C

• Class I Elements: Class I elements, also known as Class I transposable elements or retrotransposons, are a type of mobile genetic element found in the genomes of various organisms, including humans. They are characterized by their mode of transposition, which involves an RNA intermediate. The process of transposition for Class I elements involves several steps:
  1. Transcription: The Class I element is transcribed into an RNA molecule.
  2. Reverse transcription: A reverse transcriptase enzyme, typically encoded by the element itself, converts the RNA molecule into complementary DNA (cDNA).
  3. Integration: The cDNA is integrated into a new location within the genome, either directly or via a DNA intermediate. Class I elements can be further divided into several subclasses based on their structure and mechanism of transposition:
  4. Long Terminal Repeat (LTR) retrotransposons: These elements contain long terminal repeat sequences at their ends and are structurally similar to retroviruses. They transpose via a virus-like particle and use an integrase enzyme for integration.
  5. Non-LTR retrotransposons: These elements lack the LTR sequences and can be further divided into two main groups: long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs). LINEs encode the proteins required for their own transposition, while SINEs rely on the proteins encoded by LINEs for their mobility.
  6. Penelope-like elements (PLEs): These are a less common type of retrotransposon found primarily in eukaryotes. They are characterized by their unique structure and reverse transcriptase. Class I elements can have significant impacts on the structure and function of genomes, as their transposition can lead to insertions, deletions, duplications, and rearrangements. While they can sometimes be harmful to the host organism, they can also contribute to genomic diversity and evolution (see also).
• Class II Elements: Class II elements, also known as Class II transposable elements or DNA transposons, are a type of mobile genetic element found in the genomes of various organisms. Unlike Class I elements, which transpose through an RNA intermediate, Class II elements move within the genome directly through a DNA-based mechanism. The transposition of Class II elements typically involves the following steps:
  1. Excision: The Class II element is excised from its original position in the genome. This process is usually mediated by a transposase enzyme, which is encoded by the transposable element itself.
  2. Integration: The excised Class II element is inserted into a new location within the genome. The transposase enzyme typically recognizes specific target sites, called terminal inverted repeats (TIRs), at the ends of the transposon, as well as a short sequence at the target site. Class II elements can be further divided into several subclasses based on their structure and mechanism of transposition:
  3. Cut-and-paste transposons: These are the most common type of Class II elements. They are characterized by their TIRs and move through a cut-and-paste mechanism, which involves the excision of the element from one location and its integration into a new location.
  4. Rolling-circle transposons: Also known as Helitrons, these elements transpose through a rolling-circle mechanism, where the transposon is replicated and inserted into a new location without excising the original copy.
  5. Composite transposons: These elements consist of two insertion sequences (IS elements) that flank a central region containing one or more genes. They can transpose as a single unit when the transposase enzyme recognizes and acts on the flanking IS elements. Like Class I elements, Class II elements can impact the structure and function of genomes through insertions, deletions, duplications, and rearrangements. They can be both beneficial and harmful to the host organism, contributing to genomic diversity, evolution, and occasionally causing genetic diseases (see also)
• Cre Recombinase: Cre recombinase is an enzyme derived from the bacteriophage P1, a type of virus that infects bacteria. It is a site-specific DNA recombinase that belongs to the integrase family of enzymes. Cre recombinase recognizes specific DNA sequences called loxP sites, which are 34 base pairs long and consist of two 13-base pair inverted repeats separated by an 8-base pair spacer region. The primary function of Cre recombinase is to catalyze the recombination between two loxP sites present in a DNA molecule. Depending on the orientation and location of the loxP sites, Cre recombinase can mediate various DNA rearrangements, such as excision, inversion, or integration of the DNA segment flanked by the loxP sites. Cre recombinase has become a valuable molecular tool in genetics and molecular biology research, particularly in the study of gene function and regulation in eukaryotic organisms, including mice and other model organisms. The Cre-loxP system allows researchers to perform conditional and tissue-specific gene knockouts, which involve the deletion or inactivation of a specific gene in a spatially or temporally controlled manner. This approach provides more precise control over gene function and helps researchers study the roles of specific genes in development, physiology, and disease. Additionally, the Cre-loxP system can be used for lineage tracing, which involves marking and tracking the progeny of specific cell populations over time, as well as for the generation of transgenic organisms and the manipulation of large genomic segments (see also).
• Co-integrate: A co-integrate is a molecular intermediate formed during the transposition of some mobile genetic elements, particularly in the case of certain bacterial transposons. The co-integrate structure arises when two separate DNA molecules, each containing a copy of the mobile genetic element, become joined together through a recombination event involving the mobile element. Here's a simplified outline of the co-integrate formation process in the context of bacterial transposons:
  1. Excision: A transposase enzyme, encoded by the transposon, recognizes the terminal inverted repeats (TIRs) at the ends of the transposon and excises the element from its original location within the donor DNA molecule.
  2. Strand exchange: The transposase enzyme mediates a strand exchange between the ends of the excised transposon and a target site in the recipient DNA molecule. This process results in the formation of a co-integrate structure, where the donor and recipient DNA molecules are fused together, with the transposon connecting them.
  3. Resolution: The co-integrate can be resolved through a process called site-specific recombination, which is typically mediated by a resolvase enzyme. This event separates the co-integrate into two individual DNA molecules, each carrying a copy of the transposon. The co-integrate formation and resolution processes contribute to the replication and dissemination of mobile genetic elements within and between genomes, thereby playing a role in bacterial evolution and the spread of antibiotic resistance genes.
• Copy-and-paste transposition model: The copy-and-paste transposition model refers to a mechanism of transposable element mobility in which the transposable element is duplicated and the new copy is inserted into a different location within the genome. This process results in an increase in the number of copies of the transposable element. The copy-and-paste model is primarily associated with Class I transposable elements, also known as retrotransposons, which use an RNA intermediate during transposition. Here's a simplified outline of the copy-and-paste transposition process for retrotransposons:
  1. Transcription: The retrotransposon is transcribed into an RNA molecule.
  2. Reverse transcription: The RNA molecule is converted into complementary DNA (cDNA) by a reverse transcriptase enzyme, which is usually encoded by the retrotransposon itself.
  3. Integration: The cDNA molecule is inserted into a new location within the genome. This step is typically mediated by an integrase or endonuclease enzyme, which may also be encoded by the retrotransposon. The original copy of the retrotransposon remains in its initial location, while the new copy is inserted elsewhere, leading to an increase in the number of copies of the element within the genome. This mechanism allows retrotransposons to proliferate within the genome, potentially contributing to genomic diversity, evolution, and, in some cases, genetic instability or diseases. In bacteria, the copy-and-paste transposition model primarily applies to a specific subset of Class I transposable elements called bacterial insertion sequences (IS elements) that use the replicative transposition mechanism. IS elements are small, simple mobile genetic elements that typically consist of a transposase gene flanked by short terminal inverted repeats (TIRs). Replicative transposition in bacteria involves the following steps:
  4. Transcription and translation: The IS element is transcribed into RNA, which is then translated into the transposase protein.
  5. Formation of a synaptic complex: The transposase binds to the TIRs of the IS element and brings the two ends of the element together to form a synaptic complex.
  6. Cleavage and replication: The transposase cleaves one strand of the donor DNA at each end of the IS element, creating free 3' hydroxyl groups. The 3' hydroxyl groups then serve as primers for DNA replication, which generates a new copy of the IS element.
  7. Strand transfer: The newly synthesized IS element is inserted into the target DNA through a process called strand transfer, in which the target DNA is cleaved, and the IS element is ligated into the new location.
  8. Repair and ligation: The gaps in the target DNA and the donor DNA are repaired by cellular DNA repair machinery, and the IS element is ligated into the new location. As a result, the original IS element remains in its initial position, while the newly synthesized copy is inserted into a different location in the genome. This process allows IS elements to proliferate within the bacterial genome, contributing to genomic diversity and evolution. However, it can also cause genomic instability, disrupt genes, or promote the transfer of antibiotic resistance genes among bacteria. It is important to note that the copy-and-paste model is distinct from the cut-and-paste model associated with Class II transposable elements (DNA transposons), which involves the excision of the element from its original location and subsequent integration into a new location without duplication.
• Copy-out–Paste-in transposition model: see above (Copy-and-paste transposition model)
• Cut-and-paste transposition model: The cut-and-paste transposition model is a mechanism by which mobile genetic elements, primarily Class II transposable elements or DNA transposons, move within the genome. In this process, the transposable element is excised from its original location and integrated into a new location in the genome without duplicating itself. This model contrasts with the copy-and-paste transposition model, where the transposable element is duplicated, and a new copy is inserted into a different location. Here's a simplified outline of the cut-and-paste transposition process for DNA transposons:
  1. Transcription and translation: The DNA transposon is transcribed into RNA, which is then translated into the transposase protein, an enzyme responsible for the mobility of the transposon.
  2. Excision: The transposase binds to the terminal inverted repeats (TIRs) at the ends of the transposon and catalyzes the excision of the element from its original position in the genome. This process typically involves the formation of a hairpin structure at the ends of the transposon and staggered cuts in the target DNA, leaving short single-stranded overhangs.
  3. Integration: The excised transposon, still bound by the transposase, is inserted into a new location within the genome. The transposase mediates the strand transfer reaction, in which the ends of the transposon are ligated to the target DNA at the new location.
  4. Repair: The cellular DNA repair machinery fills in the single-stranded gaps at the site of integration and repairs the donor site from which the transposon was excised. This process typically results in the duplication of a short target site sequence flanking the integrated transposon. The cut-and-paste transposition model enables DNA transposons to move within the genome, contributing to genomic diversity, evolution, and, in some cases, genetic instability or diseases. However, unlike the copy-and-paste model, the cut-and-paste mechanism does not increase the number of transposon copies in the genome.

D

• Direct Repeats (DRs): In the context of transposable elements, direct repeats (DRs) are short DNA sequences that flank the mobile genetic element and are created as a consequence of the transposition process. These direct repeats are not part of the transposable element itself, but rather are a result of the integration mechanism. Direct repeats are generated during the integration of both Class I (retrotransposons) and Class II (DNA transposons) transposable elements:
  1. Class I transposable elements (retrotransposons): When a retrotransposon is reverse-transcribed and integrated into a new location in the genome, the target DNA is cleaved in a staggered manner, leaving short single-stranded overhangs. After the integration, the cellular DNA repair machinery fills in the gaps and ligates the DNA. This process results in the duplication of the target site sequence on either side of the integrated retrotransposon, creating direct repeats.
  2. Class II transposable elements (DNA transposons): During the cut-and-paste transposition process, the transposase enzyme binds to the terminal inverted repeats (TIRs) at the ends of the DNA transposon and catalyzes the excision and subsequent integration of the element into a new location. The target DNA is also cleaved in a staggered manner, and the transposon is ligated into the new site. The gaps left by the integration are filled by the cellular DNA repair machinery, resulting in the duplication of the target site sequence and the formation of direct repeats flanking the integrated transposon. These direct repeats are important for several reasons:
  3. They are a signature of the transposition event and indicate the presence of a transposable element in the genome.
  4. They may facilitate the excision of the transposable element during future transposition events, as some transposases can recognize and bind to direct repeats, enabling the enzyme to excise the element from its current location.
  5. Direct repeats can mediate genomic rearrangements, such as deletions, duplications, or inversions, if recombination occurs between the direct repeats flanking two different transposable elements. It is essential to distinguish direct repeats from the terminal inverted repeats (TIRs) that are part of the transposable element itself. While TIRs are found at both ends of DNA transposons and are recognized by the transposase enzyme, direct repeats are a result of the integration process and are found outside the transposable element in the flanking genomic DNA.
• DDE Domain: The DDE domain is a highly conserved catalytic domain found in the transposase enzymes of many Class II transposable elements, also known as DNA transposons. The DDE domain is named after the three conserved acidic amino acid residues (typically Aspartate-Aspartate-Glutamate or D-D-E) that are crucial for its function. These residues coordinate divalent metal ions, usually magnesium or manganese, which are essential for the catalytic activity of the transposase enzyme. Transposases with a DDE domain are responsible for the mobility of DNA transposons through the cut-and-paste mechanism. During transposition, the DDE domain mediates the following steps:
  1. Recognition and binding: The transposase, containing the DDE domain, recognizes and binds to the terminal inverted repeats (TIRs) at the ends of the DNA transposon.
  2. Excision: The DDE domain catalyzes the cleavage of the phosphodiester bonds at both ends of the transposon, releasing it from its original location in the genome. This process is facilitated by the divalent metal ions coordinated by the conserved D-D-E residues.
  3. Integration: The DDE domain also catalyzes the strand transfer reaction, in which the ends of the excised transposon are ligated to the target DNA at a new location. This reaction is also facilitated by the divalent metal ions coordinated by the D-D-E residues. The DDE domain is not limited to DNA transposons. It is also found in the integrase enzymes of retroviruses and certain retrotransposons (Class I transposable elements), where it plays a similar role in catalyzing the integration of the reverse-transcribed cDNA into the host genome. The conservation of the DDE domain across various mobile genetic elements highlights the fundamental importance of this catalytic domain in the transposition process and the evolution of mobile genetic elements across different organisms.
• Donor Primed Replicative Transposition (DPRT): Donor primed replicative transposition is a mechanism used by certain transposable elements, particularly bacterial insertion sequences (IS elements), to move within the genome through a copy-and-paste process. In this model, the transposon is duplicated, and a new copy is inserted into a different location, leaving the original copy in its initial position. This process is also known as replicative transposition. Here's a simplified outline of the donor primed replicative transposition process:
  1. Transcription and translation: The transposable element, such as an IS element, is transcribed into RNA, which is then translated into the transposase protein. This enzyme is responsible for the mobility of the transposable element.
  2. Formation of a synaptic complex: The transposase binds to the terminal inverted repeats (TIRs) at the ends of the transposable element and brings the two ends of the element together to form a synaptic complex.
  3. Cleavage and replication: The transposase cleaves one strand of the donor DNA at each end of the transposable element, creating free 3' hydroxyl groups. The 3' hydroxyl groups then serve as primers for DNA replication, which generates a new copy of the transposable element.
  4. Strand transfer: The newly synthesized transposable element is inserted into the target DNA through a process called strand transfer. In this process, the target DNA is cleaved, and the transposable element is ligated into the new location.
  5. Repair and ligation: The gaps in the target DNA and the donor DNA are repaired by the cellular DNA repair machinery, and the transposable element is ligated into the new location. As a result, the original transposable element remains in its initial position, while the newly synthesized copy is inserted into a different location in the genome. This mechanism allows mobile genetic elements, such as IS elements, to proliferate within the genome, contributing to genomic diversity and evolution. However, it can also cause genomic instability, disrupt genes, or promote the transfer of antibiotic resistance genes among bacteria.

G

• Group II introns: Group II introns are a class of self-splicing introns found in the genomes of bacteria, archaea, and eukaryotic organelles, such as mitochondria and chloroplasts. Introns are non-coding sequences within genes that must be removed during the process of RNA splicing to generate mature, functional RNA molecules. Group II introns are distinct from other types of introns, such as group I introns and spliceosomal introns, due to their unique structural and functional characteristics. Group II introns have several key features:
  1. RNA structure: Group II introns fold into a highly conserved secondary and tertiary RNA structure composed of six domains (labeled DI to DVI). These domains are organized around a central catalytic core that mediates the splicing reaction. The conserved structure of group II introns enables them to perform their self-splicing function.
  2. Self-splicing mechanism: Group II introns are capable of self-splicing, meaning that they can catalyze their own removal from precursor RNA molecules without the need for additional protein factors. The splicing reaction occurs through a two-step transesterification mechanism, which results in the excision of the intron and the ligation of the flanking exons.
  3. Mobility: Some group II introns are mobile genetic elements that can move within the genome through a process called retrohoming or retrotransposition. Mobility is facilitated by an intron-encoded protein (IEP) that has reverse transcriptase, RNA splicing, and sometimes endonuclease activities. During retrohoming, the IEP binds to the intron RNA and promotes reverse transcription of the excised intron into cDNA, which is then integrated into a new genomic location, usually at a homologous target site. This process is similar to the mobility of retrotransposons (Class I transposable elements).
  4. Evolutionary significance: Group II introns are thought to have played a role in the evolution of eukaryotic spliceosomal introns, as they share similarities in their splicing mechanisms and the conserved sequences at their 5' and 3' splice sites. It has been proposed that the spliceosome, a large ribonucleoprotein complex responsible for the splicing of eukaryotic nuclear pre-mRNA, may have evolved from group II introns and their associated proteins. Although group II introns are not as prevalent as spliceosomal introns in eukaryotic nuclear genomes, they play important roles in the gene expression and genome evolution of bacteria, archaea, and eukaryotic organelles. Moreover, their unique self-splicing and mobility properties have made them an interesting subject of study for molecular biologists and evolutionary biologists alike (see also).
• Genome decay: Genome decay is a process that occurs when an organism's genome undergoes genetic deterioration over time, usually as a result of mutation accumulation, deletion of functional genes, or a decrease in the efficacy of natural selection. Genome decay can lead to the loss of gene function, reduction in genome size, and, in some cases, the eventual extinction of a species or population. Genome decay is often observed in the genomes of parasites, endosymbionts, and organisms that have recently undergone a major shift in lifestyle or habitat. Several factors can contribute to genome decay:
  1. Genetic drift: In small populations, random fluctuations in the frequency of genetic variants can lead to the fixation of slightly deleterious mutations. As these mutations accumulate over time, the overall fitness of the population may decrease, contributing to genome decay.
  2. Relaxed selection: When an organism experiences a significant change in its environment or lifestyle, such as adopting an obligate parasitic or endosymbiotic lifestyle, some genes may no longer be essential for survival. In such cases, the selective pressure to maintain these genes is reduced, leading to the accumulation of deleterious mutations and eventual gene loss.
  3. Muller's ratchet: This phenomenon occurs in asexual populations or populations with low rates of recombination. In these cases, deleterious mutations can accumulate in the genome due to a lack of genetic recombination, which would otherwise allow for the removal of harmful mutations through recombination with other individuals.
  4. Repetitive elements and transposons: The presence of repetitive elements and transposable elements in the genome can contribute to genome decay through the promotion of chromosomal rearrangements, such as deletions, duplications, and inversions. These rearrangements can lead to the disruption of functional genes or regulatory regions, resulting in the loss of gene function. Genome decay can have various consequences for an organism:
  5. Loss of gene function: As functional genes accumulate deleterious mutations or are deleted from the genome, the organism may lose the ability to perform certain biological processes, potentially affecting its overall fitness.
  6. Reduced genome size: Genome decay can lead to a reduction in genome size as nonessential genes are lost. This is often observed in the genomes of endosymbionts and parasites, which have smaller genomes compared to their free-living relatives.
  7. Increased dependency: In the case of parasites and endosymbionts, genome decay can lead to an increased dependency on their host for the provision of essential nutrients and metabolites, as the genes required for their synthesis are lost.
  8. Extinction: In extreme cases, the accumulation of deleterious mutations and gene loss due to genome decay can lead to the extinction of a species or population, as its overall fitness decreases to a point where it can no longer survive or reproduce. Understanding genome decay is essential for studying the evolution and adaptation of organisms, particularly in the context of host-parasite and host-endosymbiont interactions. Additionally, knowledge of genome decay can inform the development of strategies for preserving genetic diversity and preventing species extinction.
• Genome Rearrangements:

H

• Horizontal gene transfer (or Lateral gene transfer):
• Homologous recombination:

I

• Inverted Repeats (IR):
• Integron: Integrons one class of Mobile Genetic Elements (MGEs) are specific genetic structure composed by genes (named as integron cassettes) that generally allow bacteria to adapt and rapidly evolve through the acquisition, stockpiling, excision, and reordering of open reading frames found the integron cassettes. The integron mobilization is mediated by site-specific recombination reactions by the integrase (see also).
• Invertases:

M

• Mobilome:
• Methylase (Methylation):

P

• Plasmidome:
• plasmid F:
• Pseudogenisation:
• Peel-and-paste (Single-strand) transposition model:
• Phage tyrosine integrase:
• Phage serine integrase:

R

• Resolution site:
• Resolvase:
• Rolling-circle transposition model:

S

• Synaptic complex:
• Serine recombinase: The serine recombinases are a family of DNA breaking and rejoining enzymes. Unlike homologous recombination, the serine recombinases promote rearrangements of DNA by breaking and rejoining strands at precisely defined sequence positions (see also).
• Serine Resolvases: The serine resolvases and the closely related invertases, are a group of site-specific recombinases that, in their native contexts, resolve large fused replicons into smaller separated ones
• Single-strand transposition:
• Site-specific recombination:

T

• Target specificity:
• Transposase:
• Transposome:
• Target Primed Replicative Transposition (TPRT):
• Tyrosine recombinase: Tyrosine site-specific recombinases (YRs) are a family of DNA breaking and rejoining enzymes which use the active site tyrosine nucleophile for DNA strand breakage (see also).

V

• V(D)J Recombination: V(D)J recombination is a process that occurs in the immune system of vertebrates, leading to the generation of diverse antigen receptor repertoires in B and T lymphocytes. While V(D)J recombination is not directly associated with transposable elements, it shares similarities with the mechanisms employed by some transposable elements, particularly in terms of the enzymes involved and the DNA cleavage and rejoining steps. V(D)J recombination involves the rearrangement of variable (V), diversity (D), and joining (J) gene segments to generate diverse immunoglobulin (Ig) genes in B cells and T cell receptor (TCR) genes in T cells. This process is mediated by the recombination-activating genes 1 and 2 (RAG1 and RAG2) that form a complex, known as the RAG recombinase, which recognizes specific recombination signal sequences (RSSs) flanking the V, D, and J gene segments. The similarities between V(D)J recombination and the mechanisms used by some transposable elements are as follows:
  1. Enzymatic machinery: RAG1, the catalytic subunit of the RAG recombinase, has structural and functional similarities with the DDE domain-containing transposases of certain DNA transposons. Both enzyme families use a DDE-like catalytic mechanism to mediate DNA cleavage and rejoining reactions.
  2. DNA cleavage: During V(D)J recombination, the RAG complex introduces a double-strand break (DSB) at the RSSs flanking the V, D, and J gene segments, much like the DSBs introduced by transposases at the ends of DNA transposons.
  3. DNA rejoining: After the DNA cleavage step, the broken DNA ends are rejoined by the non-homologous end-joining (NHEJ) pathway, a cellular DNA repair mechanism. Similarly, DNA transposons are often integrated into new genomic locations through the repair of DSBs by the NHEJ pathway. It is important to note that, despite these similarities, V(D)J recombination and transposable element activity are distinct processes with different biological functions. V(D)J recombination is a tightly regulated process essential for generating immune receptor diversity, whereas transposable elements are mobile genetic elements that can move within the genome and contribute to genomic diversity, evolution, and, in some cases, cause genomic instability. There is evidence suggesting that the RAG1 and RAG2 genes may have evolved from an ancient transposon or transposase gene, supporting the idea that the V(D)J recombination machinery has co-opted a mechanism originally used by mobile genetic elements for a different, essential function in the adaptive immune system.

X

• Xer Site-Specific Recombination: Xer site-specific recombination is a process that occurs in bacteria and involves the resolution of chromosome dimers, which can arise during DNA replication. This recombination mechanism is essential for maintaining the proper segregation of chromosomes during cell division. The Xer recombination system consists of two site-specific recombinases, XerC and XerD, which act on specific DNA sequences called dif sites. Chromosome dimers can form when homologous recombination occurs between two circular sister chromosomes, resulting in the formation of a single circular DNA molecule with two copies of the bacterial chromosome. This can pose a problem during cell division, as the dimeric chromosome cannot be properly segregated between the daughter cells. The Xer site-specific recombination system resolves this issue through the following steps:
  1. Recognition: The XerC and XerD recombinases recognize the dif site, a short DNA sequence that is typically located near the replication terminus of the bacterial chromosome.
  2. Synapsis: XerC and XerD bind to their respective binding sites within the dif site and bring the two dif sites together, forming a synaptic complex.
  3. Strand exchange: The recombinases catalyze a series of strand exchange reactions, in which XerC cleaves one strand of each dif site and exchanges the DNA strands between the two dif sites, followed by XerD-mediated cleavage and strand exchange of the complementary strands.
  4. Resolution: The strand exchange reactions result in the separation of the dimeric chromosome into two monomeric chromosomes, each containing a single copy of the bacterial genome. Xer site-specific recombination is essential for proper chromosome segregation and cell division in bacteria, ensuring the maintenance of genome stability. The Xer recombination system is highly conserved among various bacterial species, highlighting its importance in bacterial genome maintenance. In addition to its role in resolving chromosome dimers, the Xer recombination system has also been implicated in other processes, such as plasmid dimer resolution, integration and excision of mobile genetic elements, and regulation of gene expression.