The nematode C. elegans has seven known active DNA transposons of which Tc1 and Tc3 are most active. We identified all Tc1 and Tc3 sequences in the Bristol N2 genome. We found that virtually all Tc1 and Tc3 elements can be individually recognised by their pattern of single nucleotide polymorphisms (SNPs). We sequenced all 30 Tc1 elements at the Bristol N2 positions in the
mut-7 mutator strain. Surprisingly, we found that at several positions, a Tc1-element was found that has a different SNP pattern than the N2 element at the same position. This new SNP pattern indicates that in the
mut-7 mutator strain sequences of several Tc1-elements are shuffled into a chimeric Tc1 element. Tc1 elements that share SNPs were found in close proximity of each other in the Bristol N2 genome. This is most likely due to local jumping of Tc1. Another indication of local hopping was found when 23
unc-22::Tc1 alleles found in mutator strain
mut-7 were sequenced; a high proportion of the Tc1 elements that jumped into the
unc-22 gene originated from the same chromosome. Tc1, Tc3 and several other related transposable elements were introduced into human HeLa cells and tested for their activity. The reconstructed fish transposon Sleeping Beauty was found to be at least an order of magnitude more active than the other elements. Mutants of the Himar1 transposon that were shown to be more active in E. coli and in vitro (Lampe et al. 1999) were also found to be more active than the original Himar1 element in HeLa cells. These observations indicate that the active elements found in nature might have a sub-optimal activity and can be mutated to increase their activity. Tc1 and Tc3 are active in somatic tissues of all C. elegansstrains, but germ-line transposition occurs only in some natural isolates. Distinct genetic loci (mut genes) underlying this difference have been mapped (Mori et al. 1988). Recently,
mut-7(
pk204), a mutant derived from Bristol N2a strain without germ-line transpositionwas cloned (Ketting et al. 1999). Besides derepressed transposition in the germ line,
mut-7 worms show resistance to RNA interference (RNAi) and cosuppression (Ketting et al. 2000). The MUT-7 protein has homology with Werner Syndrome Helicase and RNaseD. In a proposed model of repression of Tc transposition in the germ line of C. elegans, the MUT-7 protein is involved in the degradation of transposase mRNA in the germ line. 42 additional mutants that allow Tc1 transposition in the germ line were found. Seventeen of these are not RNAi-resistant. We are mapping these mutants using a high density map of single nucleotide polymorphisms (SNPs). - Ketting, R.F., Haverkamp, T.H.A., van Luenen, H.G.A.M. and Plasterk, R.H.A. (1999). Mut-7 of C. elegans, required for transposon silencing and RNA interference, is a homolog of Werner Syndrome helicase and RnaseD. Cell 99, 133-141. - Ketting, R.F. and Plasterk, R.H.A. (2000). A genetic link between cosuppression and RNA interference in C. elegans. Nature, in press. - Lampe, D.J., Akerley, B.J., Rubin, E.J., Mekalanos, J.J., and Robertson, H. (1999). Hyperactive transposase mutants of the Himar1 mariner transposon. Proc. Natl. Acad. Sci. USA 96, 11428-11433. - Mori, I., Moerman, D.G., and Waterston, R.H. (1988). Analysis of a mutator activity necessary for germ line transposition and excision of Tc1 transposable elements in Caenorhabditis elegans. Genetics 120, 397-407.