Mobile genetic elements: the agents of open source evolution

Abstract

Prokaryotes transfer DNA between cells by three processes: transformation, transduction and conjugation. Transduction and conjugation depend on specialized mobile genetic elements (MGEs), which include most large plasmids and certain bacteriophages (phages). Prokaryotes also possess a third class of MGEs called transposons. These elements can move and rearrange chromosomal DNA in the cell. Transposons move from cell to cell through plasmids, phages, or their derivatives called integrative conjugative elements (ICEs). MGEs can mediate intra- or intercellular DNA trafficking because they have unique (core or backbone) genes that allow them to replicate independently of the cellular chromosome, to engage in homologous or non-homologous recombination, and to extrude (plasmid) or package (phage) DNA for efficient movement between cells. In addition to their core genes, MGEs typically carry several different accessory genes that provide their host cell with a selective advantage, such as antibiotic resistance, virulence factors, or unusual metabolic pathways. Indeed, most medically and economically important bacterial phenotypes are encoded by MGEs. Although MGEs are the main agents of horizontal gene transfer (HGT), relatively few have been sequenced and analysis of their genomic and phylogenetic properties lags behind that of organismal chromosomes. Specifically, the major databases do not curate plasmid and phage nucleic acid or protein sequences. Sequencing MGE genomes presents unique challenges because phages require suitable hosts for propagation and plasmids must be physically separated from each other and from the host chromosomal DNA. The relatively small size of MGEs (∼5–500 kb) and their varied GC content thwart current automated annotation algorithms. These challenges can be viewed as an opportunity to devise technical and bioinformatics tools for high throughput analysis of MGEs. This is important because understanding prokaryotic evolution requires knowledge of the agents that mediate this process. Such knowledge is essential for controlling problems such as the emergence of highly virulent antibiotic multi-resistant strains.