Chromosomal transposition

Horie K, Kuroiwa A, Ikawa M, Okabe M, Kondoh G, Matsuda Y, Takeda J (2001) Efficient chromosomal transposition of a Tcllmariner-hke transposon Sleeping Beauty in mice. Proc Natl Acad Sci USA 98 9191-9196. 

Transposons are mobile DNA elements (sizes 2.5-23 kbp) that move from one place to another in the chromosome or onto extrachromosomal genetic elements within the same cell. They are flanked by inverted repeats at then-ends and encode among other proteins a transposase that is needed for the transposition process. Resistance genes in the transposon are often parts of integrons. These are structures that cany an integrase responsible for the insertion of the resistance gene cassettes into the integron. 

Besides unequal crossover and transposition, a third mechanism can effect rapid changes in the genetic material. Similar sequences on homologous or nonhomol-ogous chromosomes may occasionally pair up and eliminate any mismatched sequences between them. This may lead to the accidental fixation of one variant or another throughout a family of repeated sequences and thereby homogenize the sequences of the members of repetitive DNA families. This latter process is referred to as gene conversion. 

Transposition occurs when transposons (genetic elements capable of moving between bacteria, plasmids or between chromosomal DNA and plasmids) migrate to confer resistance determinants to another organism. 

The transfer of resistance can be achieved by conjugation, transduction, and transformation. There is also a phenomenon of transposition by which resistance determinants pass from one plasmid to another or to a chromosome or to a bacteriophage, thus allowing construction of new plasmids under the pressure of new antibiotic exposure. 

The hallmark and molecular characteristic of progression is karyotype instability. This is due to disruption of mitotic apparatus, alteration of telomere function, DNA hypomethylation, chromosome translocations and recombination, gene amplification, and gene transposition. There is also alteration of mismatch repair genes in some cancers. 

Some well-characterized eukaryotic DNA transposons from sources as diverse as yeast and fruit flies have a structure very similar to that of retroviruses these are sometimes called retrotransposons (Fig. 26-33). Retro-transposons encode an enzyme homologous to the retroviral reverse transcriptase, and their coding regions are flanked by LTR sequences. They transpose from one position to another in the cellular genome by means of an RNA intermediate, using reverse transcriptase to make a DNA copy of the RNA, followed by integration of the DNA at a new site. Most transposons in eukaryotes use this mechanism for transposition, distinguishing them from bacterial transposons, which move as DNA directly from one chromosomal location to another (see Fig. 25-43). 

If transposons cause human mutation in significant numbers, this will necessitate some revision in mutagenicity testing. The mechanisms of transposition may be more akin to those of crossing-over. It is quite likely that many chemicals that induce base substitutions or chromosomal breaks may have little influence on transpo son-induced mutation, whereas other chemicals may affect transposons specifically. In this regard, it is interesting that some transposons act exclusively in germ cells, but not in somatic cells. 

It is possible that the kinds of chemicals that affect the transposition process differ from those causing nucleotide changes and chromosomal breakage. The mechanisms may be more similar to those of crossing-over than to those of mutation, and the target might be a protein, rather than DNA. Very little is known about which chemicals increase and which decrease the rate of transposition. 

Little can usefully be said today as to how this information bears on mutagen testing systems. But chemicals that affect transposition may be as important as those which affect base changes or chromosomal breakage. If so, it will be necessary to design test systems for finding and assessing the importance of such chemicals. 

Spradling, A. C. and G. M. Rubin. (1982) "Transposition of cloned P elements into Drosophila germ line chromosomes." Science 218 341-347. 

Several bacterial transposons, referred to as insertion elements (ISelements), consist only of a gene that codes for a transposition enzyme (i.e., transposase), flanked by short DNA segments called inverted repeats (Figure 18.16). (Inverted repeats are short palindromes.) More complicated bacterial transposable elements, called composite transposons, contain additional genes, several of which may code for antibiotic resistance. Because transposons can jump between bacterial chromosomes, plasmids, and viral genomes, transpositions are now believed to play an important role in the spread of antibiotic resistance among bacteria. 

In replicative transposition, a replicated copy of a transposable element is inserted into a new chromosome location in a process that involves the formation of an intermediate called a cointegrate. In nonreplicative transposition, sequence replication does not occur, that is, the transposable element is spliced out of its donor site and inserted into the target site. The donor site must be repaired. 

---