Title: Transposable Elements Post by: selfstudy on Sep 23, 2012 Discuss the similarities and differences of transposable elements in E. coli, yeast, plants, and Drosophila. How does it act and jump around in DNA?
Title: Re: Transposable Elements Post by: sperl on Sep 23, 2012 Jumping Genes: Transposable Genetic Elements The term transposable genetic element is the most generic term used to describe a genetic element that can occasionally move (transpose) from one position on a chromosome to another position
Specific types of these elements have other names, including
Such elements often cause abnormalities in gene function at the loci where they insert--most often by disrupting normal expression of the gene.
Tranposable Genetic Elements were first discovered and described in corn by Barbara McClintock, who won the Nobel Prize in Physiology or Medicine in 1983 for her lifelong work. Transposable elements were not isolated at the molecular level until they were studied in yeast and Drosophila. Discovery of Tranposable Elements in Corn (Zea mays) In 1938, Marcus Rhoades reported unexpected (non-Mendelian) ratios in certain corn crosses.
A second hypothesis was proposed:
This still didn't explain the dotted kernels. Could the dots have resulted from somatic mutations? Maybe...but there would have had to be a tremendous number of separate somatic mutations to account for all those dots. Rhoades found a male corn plant in which the anthers exhibited the dotted pigment pattern. He used pollen from these to test cross with a1a1 females. Some of the progeny were completely pigmented. This suggested that something in the dotted individuals' genes could somehow "reawaken" the ability to produce pigment in the dotted individuals offspring--but not always. What was going on?
The Ds element In the 1940s, Barbara McClintock noted in her cytological studies of corn chromosomes that in one strain of corn, chromosome 9 readly broke at a specific site. She hypothesized that the break was due to the presence of two genetic factors she named >Ds (for "Dissociation"--this one was located at the breakage site) and Ac (for "Activator"--because the Ds site would not break unless Ac was present). But when she tried to map them...they wouldn't hold still! From this, she predicted that the two elements were mobile, and could actually change places within the genome and She also found rare, unusual and unexpected corn kernel phenotypes in the offspring of her corn crosses:
Autonomous and Nonautonomous Elements
2. nonautonomous elements (which need the input (i.e., enzymatic product) of a separate element in order to transpose). In Rhoades' early study, Dt was that separate element: it supplied the factors promoting the transposition of a gene segment, and insertion of that segment into the pigment gene (A) disrupted the wild type allele's (A1) function, causing the mutant, unpigmented a1 phenotype. Insertion of an autonomous element is unstable, because it can direct its own transposition over and over. The mutation can occur in each generation; the allele produced by the insertion is called a mutable allele because of its instability. Insertion of a nonautonomous element is stable, because it needs the products of the autonomous element in order to transpose and produce the mutant allele. Let's look: And the kicker: Rarely, an Ac type was sometimes found to transform into the Ds type, apparently because the Ac element spontaneously turned into a Ds element. (This could mean that Ds is simply a mutant version of Ac that has lost the ability to encode the elements that allow it to jump around.) When McClintock first reported her findings in the 1960s, most people believed that this was something unique to corn. But later, as transposable elements were discovered in E. coli, yeast, and higher organisms, it became apparent that she had been the first to describe a phenomenon that was far more universal, suggesting that genomes were far more dynamic than first supposed. In 1983, she was awared the Nobel Prize in Physiology or Medicine for her early work on corn transposons. Several models have been proposed for transposon insertion mechanism have been proposed. The simplest and most elegant may be that of J. Shapiro. It partly explains the presence of direct and/or inverted repeats where transposons insert. Insertion Sequences: Prokaryotic Transposable Elements Insertion sequences (IS) were first discovered in the gal operon of E. coli, and were physically located because viruses carrying the bacterial gene in both mutated and wild type forms could be separated in a centrifuge: the mutants had an extra piece of DNA inserted, making them denser. When an IS appears in any of the three genes of the gal operon (E for epimerase, T for transferase and K for kinase), the normal transcription of the gene is disrupted. Insertion of an IS affects only the transcription of the genes downstream from the insertion. For example, if the IS occurs late in the E gene, the T and K genes might be disrupted, but the E might not be, and epimerase is still manufactured. This phenomenon is known as a polar mutation, since there is directionality to the transcriptional effects. Transposons: More Prokaryotic Mischief In the 1950's a strain of Shigella bacteria appeared in Japanese hospitals. The normal strains of this bacterium are sensitive to a wide spectrum of antibiotics. But a Shigella strain isolated from patients with a severe dysentery, was discovered to be resistant to most antibiotics. The multiple-drug resistance phenotype was apparently inherited as a single package--and not only by other Shigella. Other bacterial species could also obtain this resistance. The problem was a self-replicating episome, a bacterial genetic element capable of
The R factor is transferred rapidly between bacteria upon conjugation. In the cytoplasm, it exists as a plasmid. As you may recall, plasmids in bacteria often carry genes that confer resistance to antibiotics If one denatures the DNA of these R Factors and allows them to slowly renature, portions of the plasmid form a stem loop. The genes conferring drug resistance are usually located on the LOOP of the stem loop. This is located between two inverted repeat (IR) sequences, which create the stem loop. The resistance genes in the loop, along with their flanking IR sequences are known as a transposon. The regions between the IR sections are known as the resistance transfer region (RTR), since that's what carries the antibiotic resistance genes. Two mechanisms for transposition are known in prokaryotes:
2. conservative - transposon is excised and reinserted elsewhere. Both mechanisms generate a repeated sequence of the target DNA (i.e., the DNA in which the transposon is inserted). Although transposons may excise without affecting surrounding DNA, they often generate a high incidence of deletions in their vicinity. These can consist of part of the element and part of the adjacent DNA. When varying lengths of the surrounding DNA are excised along with the transposon, imprecise excision is said to have taken place. When the transposon is excised and deleted portions of the adjacent DNA are restored, precise excision is said to have taken place. Imprecise excision is far more common than precise excision. Phage µ This temperate virus (a bacteriophage) inserts into the genome of E. coli. If more than one µ is present, they can cause deletions, insertions and translocations of the host's chromosome if both excise at once. µ replicates with the host c'some, and generally does not form a plasmid. Transposable Genetic Elements in Other Eukaryotes Transposable Genetic Elements have also been found in yeast. Among them are
As much as 10% of Drosophila's genome may consist of families of dispersed, repetitive DNA sequences that move about as discrete units. Three general types are known and named:
Let's have a closer look at P Elements P Elements were first discovered due to a phenomenon--observed in controlled laboratory matings--known as hybrid dysgenesis (a fancy term for "many things wrong with the hybrid") in offspring produced in a cross of M (maternal) cytotype females (known in the lab only) and P (paternal/wild type) cytotype males. Problems included sterility, and appearance of weird mutations. The Matings:
M male x P female --> normal offspring
Modern Transposable Genetic Vocabulary The disrupted gene is said to be nonautonomous. Its expression depends not only on its own existence, but also on the action of the controlling elements (and the presence/absence of the regulator). A gene that is always potentially turning on and off via the insertion of a receptor element (unpredictable though it might be) is said to be autonomous. In such a gene, it is probable that the regulator gene (Ac, for example) has actually inserted itself into the target gene and does the inactivation (by jumping in) or activation (by jumping out) all by itself. A World of Eukaryotic TGEs As investigators search across species, it is becoming apparent that large genomes have tremendous numbers of transposable elements, and may even be composed mostly of transposable elements. This may help explain the C-value paradox: There appears to be little correlation between the size of an organism's genome and its biological complexity. Nearly half of the human genome appears to consist of transposable elements, mostly long interspersed elements (LINEs) and short interspersed elements (SINEs). Most of these can no longer move about, but retain the vestiges of former mobility (e.g., inverted repeats). A vast number also are included only in introns, and are excised and never transcribed. They are evolutionary relics rendered harmless by the points of their insertion and by the host's regulatory mechanisms. A few elements, however, are still able to move around, and some are known to be responsible for causing human disorders by inserting into specific locations: This is likely to be only small, initial list. More are undoubtedly going to be found. In grasses used by humans for grain production, differences in genome size can largely be attributed to different quantities of inserted LTR transposons. Except for the transposon regions, the different grasses show a great deal of synteny in their genomes.
Like any good parasite, a smart transposon doesn't harm its host. The ones that persist are those that have landed in genetic safe havens: areas of the genome where there are few functional genes. The transposons just hang out and are replicated--the ultimate freeloading passengers. So maybe in the long run, we'll be glad of our little passengers, and they'll eventually be paying their way by means we can't yet foresee. Title: Re: Transposable Elements Post by: selfstudy on Sep 23, 2012 WOW. Thank you ;D
|