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Linearisation of Circular Chromosomes During Bacterial Evolution

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Linearisation of Circular Chromosomes During Bacterial Evolution FEMS Microbiology Letters 186 (2000) 143^150 www.fems-microbiology.org MiniReview A new beginning with new ends: linearisation of circular chromosomes during bacterial evolution Jean-Nicolas Vol¡ a;*, Josef Altenbuchner b a Physiologische Chemie I, Biozentrum der Universita«tWu«rzburg, Am Hubland, D-97074 Wu«rzburg, Germany b Institut fu«r Industrielle Genetik, Universita«t Stuttgart, Allmandring 31, D-70569 Stuttgart, Germany Received 20 December 1999; received in revised form 1 March 2000; accepted 1 March 2000 Abstract Bacterial circular chromosomes have sporadically become linearised during prokaryote evolution. Unrelated bacteria, including the spirochete Borrelia burgdorferi and the actinomycete Streptomyces, have linear chromosomes. Linear chromosomes may have been formed through integration of linear plasmids. Linear chromosomes use linear plasmid strategies to resolve the `end-of-replication problem', but they have generally retained from their circular ancestors a central origin of replication. Streptomyces linear chromosomes are very unstable and at high frequency undergo amplifications and large deletions, often removing the telomeres. At least in Streptomyces, chromosome linearity is reversible: circular chromosomes arise spontaneously as products of genetic instability or can be generated artificially by targeted recombination. Streptomyces circularised chromosomes are very unstable as well, indicating that genetic instability is not confined to the linearised chromosomes. Bacterial linear chromosomes may contain telomere-linked regions of enhanced genomic plasticity, which undergo more frequent genetic exchanges and rearrangements and allow differential evolution of genes, depending on their chromosomal location. ß 2000 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved. Keywords: Linear chromosome; Bacterial telomere; Streptomyces; Borrelia; Genetic instability; Chromosome circularization 1. Introduction chromosome of the obligate intracellular proteobacterium Coxiella burnetii suggests linearity [5]. In eukaryotes, mi- The distinction that prokaryotic chromosomes are cir- tochondria and chloroplasts generally have circular chro- cular and eukaryotic nuclear chromosomes are linear has mosomes, a conformation consistent with their prokary- been challenged by the discovery of linear chromosomes in otic origin. Interestingly, these organelles have several unrelated bacterial species. Pulsed-¢eld gel electro- occasionally linearised their chromosome as well [6,7]. Lin- phoresis allows the separation of megabase-sized DNA ear plasmids have been detected in Borrelia and Strepto- fragments in agarose gels [1]. Using this technique, the myces, as well as in several bacteria with circular chromo- ¢rst linear bacterial chromosome was discovered in the somes [6]. spirochete Borrelia burgdorferi, the agent of Lyme disease Although chromosome circularity may have been se- [2]. The linearity of the chromosome of the antibiotic-pro- lected during prokaryote evolution, the most parsimonious ducing actinomycete, Streptomyces, was ¢rst demonstrated hypothesis explaining the distribution of linear and circu- in Streptomyces lividans [3] and then generalised to other lar chromosomes in bacteria is to assume that circular species. Agrobacterium tumefaciens, the causal agent of chromosomes have been linearised independently in sev- crown gall disease, harbours one circular chromosome eral bacterial lineages (Fig. 1). Chromosome linearisation and one non-homologous large linear DNA molecule. might have interesting consequences for di¡erent DNA This linear molecule, which is almost devoid of auxotro- processes, including replication termination, replicative phic markers, was assumed to correspond to a linear chro- transposition and conjugation [8]. mosome [4]. In addition, the macrorestriction map of the 2. Replication origin * Corresponding author. Tel.: +49 (931) 888 4165; Fax: +49 (931) 888 4150; E-mail: vol¡@biozentrum.uni-wuerzburg.de Generally, linear bacterial chromosomes have a central 0378-1097 / 00 / $20.00 ß 2000 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved. PII: S0378-1097(00)00118-X FEMSLE 9353 27-4-00 144 J.-N. Vol¡, J. Altenbuchner / FEMS Microbiology Letters 186 (2000) 143^150 Fig. 1. Distribution of circular and linear chromosomes in prokaryotes. Symbols: circles, circular chromosomes; bars, linear chromosomes. Question marks indicate that the genome of Rhodococcus fascians has been reported alternately as linear and circular and that linearity of Coxiella chromosome has been suggested only by pulsed-¢eld gel electrophoresis analysis. The number of chromosomes is not taken into account. The lengths of the branches of the tree do not re£ect the degree of relationship between genera. References on circularity and linearity of chromosomes as well as on prokaryote taxonomy can be found on the server of the National Center for Biotechnology Information (NCBI, http://www.ncbi.nlm.nih.gov/Entrez/Genome/ org.html, http://www.ncbi.nlm.nih.gov/Entrez/medline.html and http://www.ncbi.nlm.nih.gov/Taxonomy/tax.html). origin of replication, oriC, presenting a genetic organisa- 3. Telomeres and chromosome replication tion similar to that of circular chromosomes. In B. burg- dorferi, replication proceeds bidirectionally from the dnaA- Because of the polarity of replication, linearised chro- dnaN-gyrB region located in the middle of the linear chro- mosomes are confronted with the new problem of copying mosome [9]. In most Streptomyces species, functional evi- their 3P extremities. Bacterial linear chromosomes and dence indicates that oriC is also located in the centre of the plasmids have adopted at least two di¡erent strategies to linear chromosome, close to the dnaA-gyrB region [10]. In complete their replication. While chromosome and plas- the chromosome of S. rimosus, however, the dnaA region mid telomeres are based on similar structural features is located non-symmetrically [11]. The replication origin of within the same bacterial genus, Borrelia telomeres are the chromosome of C. burnetii has not been determined clearly di¡erent from Streptomyces telomeres. Borrelia lin- unequivocally. A putative oriC is £anked on one side by ear chromosomes have covalently closed hairpin structures genes found in proximity to other bacterial chromosome at their termini that are similar to those reported for Bor- origins, including gidB, gidA, 50k, rnpA and rpmH.In relia linear plasmids and for Escherichia coli prophage contrast, genes such as dnaA, dnaN, recF or gyrB are N15 [6,12,13]. Such telomeric structures have also been not present on the other side. This putative origin is not found in some animal viruses (e.g. poxviruses [6]) and at located centrally on the chromosome but closer to one end the end of certain yeast linear mitochondrial DNA (e.g. in [5]. On the other hand, gyrA, which is associated with the closely related genera Williopsis and Pichia [7]). several bacterial oriC, occupies a central position on the Replication of Borrelia linear molecules might involve a physical map of the C. burnetii chromosome. Hence, the circular intermediate [6,9,13]. Replication may proceed di- geometry of the chromosome and the position of the ma- rectly from the linear form of the chromosome, leading to jor origin of replication need to be clari¢ed in this bacte- the formation of a dimeric circular intermediate in which rium. unit-length genomes are connected by duplicated hairpin FEMSLE 9353 27-4-00 J.-N. Vol¡, J. Altenbuchner / FEMS Microbiology Letters 186 (2000) 143^150 145 loop sequences and are subsequently resolved into mono- linear molecules might create a circular linkage map. mers. Alternatively, terminal hairpins might be nicked in a Markers located at opposite ends of each mating mole- way generating cohesive ends and allowing circularisation cules tend in this way to end up in the same recombinant before replication [6,9,13]. molecule, resulting in apparent genetic linkage. Indeed, In contrast, Streptomyces linear chromosomes and plas- Wang et al. provided evidence for such a phenomenon mids carry proteins bound to the 5P end of the double- in S. lividans-S. coelicolor conjugation experiments [19]. stranded telomeres. This was ¢rst revealed by electropho- These Streptomyces species are related su¤ciently to allow retic retardation of linear DNA molecules when pulsed- recombination between their chromosomes but di¡er in ¢eld gel electrophoresis was performed without protease their telomere sequences and macrorestriction patterns so treatment [3]. Similar telomeric structures have been re- that it can be determined which part of the recombinant ported in several bacteriophages, including Bacillus subtilis chromosome comes from which parent. Recombinant phage x29, E. coli phage PRD1 and Streptococcus pneu- chromosomes having one S. coelicolor telomere and one moniae phage HB-3, in several fungal and plant mitochon- S. lividans telomere (mixed ends) should indicate an odd drial linear plasmids, and in adenoviruses [6]. Telomeric number of crossovers, while recombinant chromosomes terminal proteins are probably involved in the completion with both ends originating from the same parent should of replication [3,14]. The 166^168-bp terminal segments of have resulted from even numbers of crossovers. The re- Streptomyces linear replicons contain conserved palin- sults obtained by Wang et al. were compatible with a dromic
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