Mobile genetic elements in animal cells and their biological significance

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Abstract
Mobile genetic elements were discovered by McClintock while analyzing unstable mutations in maize. The structural and functional studies of such elements became possible after their cloning, first from the genome of Drosophila melanogaster. In particular, Ilyin et al, demonstrated the varying location of the described elements in D. melanogaster chromosomes, thus providing the first evidence of their mobility. Mobile elements comprise a significant part of the genetic material in D. melanogaster (not less than 10%). Several classes of mobile elements do exist. Mobile dispersed genetic elements (mdg elements) are among the best characterized ones. Mdg elements are represented in the genome by dozens of families, each consisting of 10-150 copies. They are very similar structurally to proviruses of endogenous retroviruses. In particular, they both contain long terminal repeats (LTRs). The nucleotide sequences of LTRs and their flanking sequences of several mdg elements were determined. Their analysis suggested mRNA reverse transcription should be involved in the mdg amplification. It has been found that putative transposition intermediates, i.e., extrachromosomal DNA copies of mdg elements, are synthesized by reverse transcriptase in D. melanogaster culture cells. Another type of mobile genes is represented by P factor and similar elements. P factor seems to encode transposase participating in direct excision and insertion of P elements themselves as well as of other mobile genes (mdg and fold-back elements). Besides these active transposons which encode the enzyme machinery for transposition, a number of other sequences which may be transposed are present in the genome. RNA synthesized on such elements can serve as a template for reverse transcriptase, and the DNA formed can then be inserted at new sites of the genome. Among such sequences are the so-called short ubiquitous repeats: B1 and B2 in mouse genome and Alu in human genome. At least in several cases, B-type sequences were located at the 3'' end of mRNA. Short repetitive sequences were also detected at the 3'' end of certain mRNA of D. melanogaster. Usually the transposition of mobile genes occur very rarely. However, under certain conditions, for example, in hybrid dysgenesis, they become more frequent. The strain with a mutation in cut locus was obtained in hybrid dysgenesis. This mutation depends on an insertion of mdg4 at the cut locus. Genetic instability in this strain is maintained for a long time. Transposition bursts were found to occur in some germ cells. In such cells, a high number of independent transposition events involving different mobile elements (mdg, P elements, FB elements) take place. The transposition bursts leading to multiple mutagenesis may play an important role in evolution creating individuals with a set of new features and facilitating their reproductive isolation. Transpositions of mobile elements may also serve as an important factor of somatic mutations. In some cases, they may become the inducers of oncogene activation leading to oncogenic cell transformation. The content of components participating in transposition is strikingly enhanced in most tumor cells. This concerns mdg transcripts, small B2 RNA and circular forms of mdg. Transposition in tumor cells may be activated to enhance the microevolution rate of tumor cells and tumor progression.