RESEARCH HIGHLIGHTS Nature Reviews Microbiology | AOP, published online 18 November 2013; doi:10.1038/nrmicro3177
ARCHAEAL BIOLOGY
Less means more for Haloferax the combined deletion of all four origins resulted in a fitness advantage
DNA replication is typically initiated at discrete sites known as origins, which serve as assembly sites for the replication machinery and thereby coordinate chromosome replication. Unlike bacteria, which use a single origin, some archaea use multiple origins, whereas viruses often rely on homologous recombination to initiate replication at nonspecific genomic sites. Hawkins et al. now show that, in the absence of origins, the archaeon Haloferax volcanii is capable of replicating its entire genome by homologous recombi nation and, unexpectedly, this is associated with a fitness advantage. To assess replication dynamics in H. volcanii, the authors obtained rep lication profiles by deep sequencing the laboratory strain H26, which was
NPG
found to have four distinct origins. The requirement for all four origins was tested by the targeted deletion of each. Pairwise growth competitions with the wild-type strain revealed that, although deletion of a single origin conferred a fitness cost, the combined deletion of all four origins resulted in a fitness advantage, which corresponded to a 7.5% increase in growth rate. So, how does replication initi ate in the absence of origins? The replication profiles of the deletion strains were consistent with originindependent initiation occurring at dispersed sites. Origin-independent replication occurs when either recombination or transcription intermediates, which are known as D-loops and R-loops, respectively, prime replication. The replication profile of the strain that lacked all four origins indicated that initiation was enriched at the highly transcribed rrnB rRNA operon (a region that has increased recombination levels), which produces D-loops and R-loops at a high frequency, suggesting that
NATURE REVIEWS | MICROBIOLOGY
they could facilitate the initiation of replication. This is analogous to DNA damage-inducible replication in Escherichia coli, which occurs in the absence of the origin oriC, but depends on the recombination protein RecA. The archaeal homo logue of RecA, RadA, was shown to be essential for replication in the H. volcanii mutant that lacked all four origins, which confirms that homologous recombination initiates replication in the absence of origins. Collectively, these data show that an entire archaeal genome can be replicated by recombinationmediated initiation at multiple chromosomal sites. Furthermore, as origin-dependent replication seems to offer no advantage in H. volcanii, the authors propose that origins are selfish genetic elements. Christina Tobin Kåhrström ORIGINAL RESEARCH PAPER Hawkins, M. et al. Accelerated growth in the absence of DNA replication origins. Nature http://dx.doi. org/10.1038/nature12650 (2013) FURTHER READING Lindås, A.-C. & Bernander, R. The cell cycle of archaea. Nature Rev. Microbiol. 11, 627–638 (2013)
VOLUME 12 | JANUARY 2014 © 2013 Macmillan Publishers Limited. All rights reserved
ARCHAEAL BIOLOGY
Less means more for Haloferax the combined deletion of all four origins resulted in a fitness advantage
DNA replication is typically initiated at discrete sites known as origins, which serve as assembly sites for the replication machinery and thereby coordinate chromosome replication. Unlike bacteria, which use a single origin, some archaea use multiple origins, whereas viruses often rely on homologous recombination to initiate replication at nonspecific genomic sites. Hawkins et al. now show that, in the absence of origins, the archaeon Haloferax volcanii is capable of replicating its entire genome by homologous recombi nation and, unexpectedly, this is associated with a fitness advantage. To assess replication dynamics in H. volcanii, the authors obtained rep lication profiles by deep sequencing the laboratory strain H26, which was
NPG
found to have four distinct origins. The requirement for all four origins was tested by the targeted deletion of each. Pairwise growth competitions with the wild-type strain revealed that, although deletion of a single origin conferred a fitness cost, the combined deletion of all four origins resulted in a fitness advantage, which corresponded to a 7.5% increase in growth rate. So, how does replication initi ate in the absence of origins? The replication profiles of the deletion strains were consistent with originindependent initiation occurring at dispersed sites. Origin-independent replication occurs when either recombination or transcription intermediates, which are known as D-loops and R-loops, respectively, prime replication. The replication profile of the strain that lacked all four origins indicated that initiation was enriched at the highly transcribed rrnB rRNA operon (a region that has increased recombination levels), which produces D-loops and R-loops at a high frequency, suggesting that
NATURE REVIEWS | MICROBIOLOGY
they could facilitate the initiation of replication. This is analogous to DNA damage-inducible replication in Escherichia coli, which occurs in the absence of the origin oriC, but depends on the recombination protein RecA. The archaeal homo logue of RecA, RadA, was shown to be essential for replication in the H. volcanii mutant that lacked all four origins, which confirms that homologous recombination initiates replication in the absence of origins. Collectively, these data show that an entire archaeal genome can be replicated by recombinationmediated initiation at multiple chromosomal sites. Furthermore, as origin-dependent replication seems to offer no advantage in H. volcanii, the authors propose that origins are selfish genetic elements. Christina Tobin Kåhrström ORIGINAL RESEARCH PAPER Hawkins, M. et al. Accelerated growth in the absence of DNA replication origins. Nature http://dx.doi. org/10.1038/nature12650 (2013) FURTHER READING Lindås, A.-C. & Bernander, R. The cell cycle of archaea. Nature Rev. Microbiol. 11, 627–638 (2013)
VOLUME 12 | JANUARY 2014 © 2013 Macmillan Publishers Limited. All rights reserved
