Transposable elements (TEs) are commonly viewed as molecular parasites producing mainly neutral or deleterious effects in host genomes through their ability to move. However, during the past two decades, major interest has been focusing on the positive contribution of these elements in the evolution of gene regulation and in the creation of diverse structural host genes. Indeed, DNA transposons carry an attractive and elaborate enzymatic machinery as well as DNA components that have been co-opted in several cases by the host genome via an evolutionary process referred to as molecular domestication. A large number of transposon-derived genes known to date have been recruited by the host to function as transcriptional regulators; however, the biological role of the majority of them remains undetermined. Our knowledge on the structure, distribution, evolution and mechanism of transposons will continue to provide important contributions to our understanding of host genome functions.
Hsmar1, one of the two subfamilies of mariner transposons in humans, is an ancient element that entered the primate genome lineage ϳ50 million years ago. Although Hsmar1 elements are inactive due to mutational damage, one particular copy of the transposase gene has apparently been under selection. This transposase coding region is part of the SETMAR gene, in which a histone methylatransferase SET domain is fused to an Hsmar1 transposase domain. A phylogenetic approach was taken to reconstruct the ancestral Hsmar1 transposase gene, which we named Hsmar1-Ra. The Hsmar1-Ra transposase efficiently mobilizes Hsmar1 transposons by a cut-and-paste mechanism in human cells and zebra fish embryos. Hsmar1-Ra can also mobilize short inverted-repeat transposable elements (MITEs) related to Hsmar1 (MiHsmar1), thereby establishing a functional relationship between an Hsmar1 transposase source and these MITEs. MiHsmar1 excision is 2 orders of magnitude more efficient than that of long elements, thus providing an explanation for their high copy numbers. We show that the SETMAR protein binds and introduces single-strand nicks into Hsmar1 invertedrepeat sequences in vitro. Pathway choices for DNA break repair were found to be characteristically different in response to transposon cleavage mediated by Hsmar1-Ra and SETMAR in vivo. Whereas nonhomologous end joining plays a dominant role in repairing excision sites generated by the Hsmar1-Ra transposase, DNA repair following cleavage by SETMAR predominantly follows a homology-dependent pathway. The novel transposon system can be a useful tool for genome manipulations in vertebrates and for investigations into the transpositional dynamics and the contributions of these elements to primate genome evolution.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.