Transposable Elements for Genetics Help (page 2)
Some genes or closely linked sets of genes can mediate their own movement from one location to another and may exist in multiple copies (sometimes hundreds or thousands) dispersed throughout the genome. These elements have been variously called jumping genes, mobile elements, insertion sequences, cassettes, and transposons; however, the formal name for this family of DNA sequences is transposable elements and their movement is called transposition.
Transposable elements can be of two different types. The first type is a relatively short DNA element that has the ability to move to a newspot in the genome. These elements generally encode one or a fewgenes, one of which is an enzyme called transposase that is required for the movement. These elements are found in both prokaryotes and eukaryotes. The second type of transposable element is one that must go through an RNAintermediate that is copied to DNA before this DNA is inserted into a new spot in the genome. These elements are termed retrotransposons or retroposons and are related to retroviruses. They are found primarily in eukaryotic organisms. Transposable elements can also transpose themselves (functional), or are unable to transpose on their own (nonfunctional).
Transposition may result in mutation and is potentially a major source of genome diversity and change. Transposable elements can move adjacent DNA sequences with them, resulting in mutation or spots for recombination events within a genome. If a transposon becomes inserted into the coding region of a gene, it interrupts the coding sequence and inactivates the expression of the gene. In addition, transposable elements may contain transcription and/or translation termination signals that block the expression of other genes downstream of the insertion site. This "one-way" mutational effect is referred to as a polar mutation. Transposition may also result in induction of oncogenic or cancer-promoting activities.
The transposable elements of bacteria fall into two major classes. Simple transposons (also called insertion sequences, or IS) carry only the genetic information necessary for their transposition (e.g., the gene for the enzyme transposase). Simple insertion sequences have no known effects beyond transposition and inac-tivation of the gene (or operon) into which they may insert. Complex or composite transposons (Tn) contain additional genetic material unrelated to transposition, such as drug-resistance genes.
The hallmark of a simple transposon is the presence of identical, inverted terminal repeat (ITR) sequences of 8–38 bp. Each type of transposon has its own unique inverted repeat. On either side of a transposon is a short (less than 10 bp) direct repeat (Fig. 11.7).
If a transposon exists in multiple copies, these direct repeats are of different base composition at each site where the transposon exists in the chromosome; the inverted terminal repeats, however, remain the same for a given transposon. The sequence into which a transposable element inserts is called the target sequence. During insertion of a transposon, the singular target sequence becomes duplicated and thus appears as direct repeats flanking the inserted transposable element. The direct repeats are not considered part of the transposon. No homology exists between the transposon and the target site for its insertion. Many transposons can insert at virtually any position in the host chromosome or into a plasmid. Some transposons seem to be more likely to insert at certain positions (hot spots), but rarely at base-specific target sites. The enzymes required for transposition are encoded in the central region of the transposon. Transposons usually generate a high incidence of deletions in their vicinity because of imprecise excision that removes some adjacent sequences along with the transposon.
Two copies of a transposable element can transpose a DNA sequence between them. For example, in bacteria, Hfr cells are formed by the integration of the sex factor F into the host chromosome. An integrated F sequence is always flanked by two copies (in direct repeat) of one of the insertion sequences located in an F plasmid.
Some complex transposons carry one or more bacterial genes for antibiotic resistance in their central regions. Because transposons can shuttle in and out of plasmids as well as chromosomes, it is thought that multiple drug resistance, characteristic of R plasmids ("R" for resistance), developed in this way. Such plasmids are easily transferred by conjugation to antibiotic-sensitive bacteria and, with the aid of natural selection, very quickly spread resistance throughout a bacterial species within a patient. Transposons do not carry genes that are essential for survival under normal conditions, but in hostile environments (e.g., in the presence of antibiotics or an immune system) the genes carried by a transposon may make the difference between life and death of the bacterial cell.
Two models of transposition in prokaryotes have been proposed, on the basis of the fate of the donor site. The transposon might be excised from the donor site, leaving no copy of itself at the donor site (conservative mode). Alternatively, the transposon might be replicated, allowing one copy to transpose to another site and leaving an identical copy at the donor site (replicative mode). Only the replicative mode could produce multiple copies at various sites in the genome. In bacteria, the number of copies of a transposon appears to be regulated, seldom exceeding 20 copies per genome. In eukaryotes, however, the copy number can be very high.
As mentioned earlier, eukaryotic cells can contain DNA elements that transpose on their own. Agood example of this type of element is the Ac-Ds system in maize.
EXAMPLE 11.8 Mobile genetic elements ("jumping genes") were first discovered in maize by Barbara McClintock in the 1950s. Insertion of the controlling element Ds into or adjacent to a locus governing kernel color inhibits the production of color and results in a colorless phenotype. Excision of Ds reverses the effect and produces colored spots on a colorless background. The Ds elements occur in different sizes as deleted forms of a larger complete element called Ac. The Ds elements are non-autonomous because they remain stationary unless an Ac element is also present, whereas Ac elements are autonomous because they can move independently. Both Ac and Ds elements have perfect inverted repeats of 11 bp at their termini, flanked by 6- to 8-bp direct repeats of the target site. Thus, Ac and Ds are transposons. Ac need not be adjacent to Ds or even on the same chromosome in order to activate Ds. When Ds is so activated, it can alter the level of expression of neighboring genes, the structure of the gene product, or the time of development when the gene expresses itself, as a consequence of nucleotide changes inside or outside a given gene. An activated Ds element can also cause chromosomal breakage, which can yield deletions or generate a bridge-breakage-fusion-bridge cycle. Several other systems like the Ac / Ds system are now known in maize. Each has a target gene that is inactivated by insertion of a receptor element into it, and a distant regulator element that is responsible for the mutational instability of the locus. The receptor and regulator elements are both considered to be controlling elements of the target gene.
The other type of element found in eukaryotic systems is the retrotransposon. The retrotransposition process begins with transcription of DNA into mRNA. The RNA is then copied by the action of a reverse transcriptase enzyme into a DNA copy (cDNA). This cDNA then integrates into a new region of the genome. The reverse transcriptase is generally one of the genes encoded by the retrotransposon. Another commonly encoded gene is integrase, an enzyme required for integration of the cDNA into the genome. Retrotransposons exist in high copy number in mammalian genomes (up to 500,000 elements making up as much as 40% of the genome). They can be short (200–200 bp) or long (3,000–8,000 bp) DNA segments. Short elements are called SINEs, for short interspersed elements and the longer ones are termed LINEs for long interspersed elements.
EXAMPLE 11.9 In a human genome, there exist about 300,000 members of a SINE sequence (approximately 300 bp) that is cut by a base-specific DNase called AluI. Members of this Alu family are related, but not identical in base sequence. Each member is flanked by direct repeats. Although transposition has not been observed for any member, the Alu family is thought to have evolved from a DNA copy of an RNA molecule that plays a role in protein synthesis. Since no function, essential or otherwise, has been attributed to this family, it may represent an example of "selfish DNA" whose function is to make copies of it self.
The most common LINE in mammals is the L1 element. The Ty element in yeast and the copia element in Drosophila are other examples of retrotransposons. Many of these elements contain genes or processed pseudogenes related to cellular and retroviral genes. Pseudogenes are nonfunctional genes with sequence similarity to a functional gene found elsewhere in the genome of an organism.
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