Preface

Linear plasmids were firstly discovered (in mitochondria of corn) approximately 25 years after the seminal, epoch-making original documentation of circular plasmids in bacteria by Joshua Lederberg and co-workers in the 1950s. This earmarked the advent of the molecular biological age. Though linear plasmids were initially regarded as rare and rather peculiar genetic elements, in the following three decades their frequency in a multitude of eukaryotic and bacterial species became evident. Despite linearity-neglecting definitions, which were even put forward in a number of textbooks, such a configuration was frequently found not only in eukaryotic and certain bacterial chromosomes but especially in extrachromosomal genetic elements of both taxa.

Linear DNA-molecules must meet the challenge of being shortened gradually during successive replication rounds; a problem that is solved for eu-karyotic chromosomes by the action of the telomerase. In microbial linear plasmid systems other, probably ancient, mechanisms are instrumental in avoiding impending losses. A great number of linear plasmids from both bacteria and fungi are so-called invertrons, which possess terminal inverted repeat sequences and 5'covalently attached terminal proteins serving as replication primers. Such a replication mode, which is assumed to already have existed before the genesis of eukarya, is conserved not only in linear plasmids but also in adenoviruses and bacteriophages. The major player in replication, the DNA-polymerase encoded by invertron type linear plasmids, displays articulate similarities to enzymes of the above viruses, unambiguously confirming the common ancestry.

Similarly, viral ancestry is obvious for the linear retroplasmids present in several fungal species. Eponymous for such elements, replication involves an RNA intermediate serving as a template for the reverse transcriptase. As for the invertron-type DNA polymerase such a key player of replication substantiates the common ancestry of retroplasmids and retroviruses, which suggests that they are remnants of primitive genetic elements occurring shortly after or in parallel with the transition from the RNA world to the DNA world.

The most convincing argument for the affinity of linear plasmids and viruses originates from elements isolated as linear plasmids in enterobacteria, which subsequently shaped up as prophage stages. Such prophages, as well as linear plasmids from Borrelia, have covalently closed hairpin termini allowing DNA

replication to proceed around the turns. Since dimeric replication intermediates require resolution, an enzyme reminiscent of type IB resolvases is encoded by Borrelia plasmids as well as linear prophages.

The biological significance of linear plasmids is rather diverse. In yeast they may encode protein toxins, which not only enable autoselection but also have the ability to eliminate competitors. In bacteria they may confer specific catabolic capabilities, antibiotic resistance or enhancement of pathogenicity. Selfish elements without any (obvious) effect on their hosts exist in yeast and filamentous fungi; in the latter they may, however, integrate into the mitochondrial DNA, eventually resulting in a molecular disease causing senescence of the host.

Progenitors of linear plasmids date back to earliest stages of evolution to which they have significantly contributed. This is indicated by the highly transmissible Streptomyces elements, which clearly contributed to genome evolution by active DNA transfer and exchange, recruitment and spread of accessory genetic information and pathways involved in secondary metabolism. Some linear plasmids may be regarded as molecular fossils, which provide us with the unique possibility to study molecular details at the earliest stages of life.

The aim ofthis volume was to assemble a collection ofreviews that comprehensively address the diverse structural and functional aspects of the rather heterogeneous group of genetic elements subsumed as "linear plasmids". We wish to express our gratitude to all authors for their substantial efforts and excellent contributions. It was their expertise in the particular areas of linear plasmid biology and their enthusiastic engagement in preparing the individual chapters that made it possible to bring together all these elements in one volume. We are grateful to Springer for giving us the opportunity to edit this book, in particular to Jutta Lindenborn from the editorial office for her support in all aspects of the publishing process.

Münster, May 2007 Roland Klassen

Friedhelm Meinhardt Alexander Steinbüchel

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