Downloaded from http://cshperspectives.cshlp.org/ on October 3, 2021 - Published by Cold Spring Harbor Laboratory Press Coevolution of the Organization and Structure of Prokaryotic Genomes Marie Touchon1,2 and Eduardo P.C. Rocha1,2 1Microbial Evolutionary Genomics, Institut Pasteur, 75015 Paris, France 2CNRS, UMR3525, 75015 Paris, France Correspondence: [email protected] The cytoplasm of prokaryotes contains many molecular machines interacting directly with the chromosome. These vital interactions depend on the chromosome structure, as a mole- cule, and on the genome organization, as a unit of genetic information. Strong selection for the organization of the genetic elements implicated in these interactions drives replicon ploidy, gene distribution, operon conservation, and the formation of replication-associated traits. The genomes of prokaryotes are also very plastic with high rates of horizontal gene transfer and gene loss. The evolutionary conflicts between plasticity and organization lead to the formation of regions with high genetic diversity whose impact on chromosome structure is poorly understood. Prokaryotic genomes are remarkable documents of natural history because they carry the imprint of all of these selective and mutational forces. Their study allows a better understanding of molecular mechanisms, their impact on microbial evolu- tion, and how they can be tinkered in synthetic biology. rokaryotic cells typically lack a clear physi- nus in the cell. As replication proceeds, DNA Pcal separation between DNA and the cyto- regions are under different states of replication plasm. The cell is therefore a complex network and are being segregated in function of the of genetic and biochemical interactions involv- growing multiple division septa. Hence, repli- ing the DNA molecules and many cellular pro- cation, segregation, and cell doubling are tightly cesses. The complexity of such interactions is linked. In prokaryotes, nascent transcripts are well illustrated by the functioning of Escherichia immediately translated by multiple ribosomes coli. In fast growing E. coli cells, the replication and, for certain membrane proteins, integration forks advance bidirectionally and very rapidly in the membrane takes place before the end from the single origin of replication to the ter- of transcription and translation. Hence, tran- minus. The cell doubles in 20 min, which is less scription, translation, and protein localization than the time required to replicate the chro- are tightly linked. Exponentially growing cells mosome (45 to 60 min). This is made possible endure intense gene expression and collisions by up to three simultaneous replication rounds, between the rapid replication fork and the rela- resulting in the presence of eight replication tively slower RNA polymerases are frequent. forks and eight origins of replication per termi- These collisions may disrupt both transcription Editor: Howard Ochman Additional Perspectives on Microbial Evolution available at www.cshperspectives.org Copyright # 2016 Cold Spring Harbor Laboratory Press; all rights reserved; doi: 10.1101/cshperspect.a018168 Cite this article as Cold Spring Harb Perspect Biol 2016;8:a018168 1 Downloaded from http://cshperspectives.cshlp.org/ on October 3, 2021 - Published by Cold Spring Harbor Laboratory Press M. Touchon and E.P.C. Rocha and replication, thereby potentially affecting all number of encoded proteins. The smallest ge- of the other above-mentioned cellular process- nomes (,500 kb) correspond to obligatory en- es. Collisions between the replication fork and dosymbionts that have arisen by reduction of RNA polymerases may result in the fork’s col- larger genomes of free-living bacteria. Some of lapse. Ensuing SOS or SOS-like responses may these genomes have fewer genes than those kick off the transfer of mobile genetic elements strictly required for autonomous life in E. coli to other cells, thereby changing their gene rep- (McCutcheon and Moran 2012). Larger ge- ertoires. The associations between all of these nomes encode complex metabolic and genetic cellular processes through their interactions networks, some of them allowing bacteria to with the chromosome result in natural selection differentiate or regroup into multicellular bod- for genome organization. The strength of selec- ies (Guieysse and Wuertz 2012). Variations in tion on a given organizational trait that is as genome size affect cellular functions in different strong as the efficiency of the interaction with ways. The gene repertoires associated with some the chromosome is important. Because many of housekeeping functions, like translation, show the above-mentioned processes are essential, little variation in the known range of genome the organization of genomes is under strong size. Gene repertoires for other functions are selection and the study of genome organization much more variable: smaller genomes are near- informs about natural history and about cell ly depleted of sensory, transport, communi- functioning. cation, and regulatory functions, reflecting nar- Prokaryotes endure high rates of rearrange- row environmental ranges (Boussau et al. 2004; ment, mutation, deletion, and accretion of ge- Konstantinidis and Tiedje 2004). Importantly, netic material. This leads to trade-offs between larger genomes are thought to engage much selection for genome organization and selection more frequently in horizontal gene transfer for genetic diversification that drive the evolu- (Cordero and Hogeweg 2009) and encode tion of the genome. A full understanding of the more transposable elements (Touchon and Ro- organization of genetic elements in the genome cha 2007). Genome size is also positively cor- (genome organization) and of the structure related with the strength of purifying selection of DNA molecules in the cell (chromosome acting on protein coding sequences (Kuo et al. structure) therefore requires multidisciplinary 2009). This suggests that natural selection is approaches, bridging genetics, genomics, bio- more efficient in larger genomes, possibly as a chemistry, and biophysics against a backdrop result of larger effective population sizes. Very of evolutionary biology. Several aspects of this large gene repertoires might in fact require effi- topic were reviewed before (Abby and Daubin cient natural selection derived from large effec- 2007; Rocha 2008; Kuo and Ochman 2009b; tive population sizes, otherwise genes would Boussau and Daubin 2010; Touzain et al. 2011; be rapidly lost by genetic drift. It is thus gener- Ptacin and Shapiro 2013). We will focus on re- ally thought that larger genomes correspond to cent findings and on aspects for which the evo- more versatile prokaryotes that are less sexually lutionary scope has, in our view, been insuffi- isolated and in which selection is more efficient. ciently emphasized. Prokaryotes are often polyploid, with cer- tain species carrying more than 100 copies of the chromosome per cell (Fig. 1). Polyploidy VARIATIONS IN GENOME STRUCTURE might increase gene dosage in very large cells, The size of prokaryotic genomes ranges from in which demand for transcription is very high around 50 kb to more than 13 Mb (Schneiker (Mendell et al. 2008), and facilitate gene ex- et al. 2007; Ishii et al. 2013; Tatusova et al. 2015). pression regulation in endosymbionts (Vinuelas These genomes are also very compact, with gene et al. 2011), which have few other means of density typically approaching 85% (Mira et al. regulating the rate of gene expression. A large 2001). There is, therefore, a direct proportion- number of identical chromosomes might also ality between the size of the genome and the diminish the stochastic effects of gene expres- 2 Cite this article as Cold Spring Harb Perspect Biol 2016;8:a018168 Downloaded from http://cshperspectives.cshlp.org/ on October 3, 2021 - Published by Cold Spring Harbor Laboratory Press The Evolution of Genome Organization A B Lesion * DNA repair C Gene conversion Figure 1. Traits associated with polyploidy in prokaryotes. The presence of multiple copies of replicons, and particularly chromosomes, has been proposed to confer several advantages. (A) It allows distributing gene expression through the entire cytoplasm in very large cells. It allows heterozygosity. In the presence of several replicons, the ratio between replicons allows gene expression regulation. (B) It allows repair by homologous recombination with other similar replicons. (C) Recombination between similar replicons also allows gene conversion and allelic exchange. Heterozygosity is indicated using distinct colors (red and black). sion, which are exacerbated when there is a sin- type of chromosome (not to be confounded gle DNA molecule (Soppa 2013). Because sister with polyploidy). Such genomes typically have chromosomes can recombine efficiently by chromosomes of very different sizes. The larger homologous recombination, polyploidy allows chromosome encodes most essential and highly transient genetic diversification by reversible expressed genes. Smaller chromosomes are also heterozygosity (Griese et al. 2011), antigenic called secondary chromosomes or chromids variation by recombination (Tobiason and Sei- (Harrison et al. 2010), and vary widely in size fert 2006), and DNA repair (Zahradka et al. and persistence in bacterial lineages. Genomes 2006). Gene conversion between variants in of the genus Burkholderia carry one, two, or different chromosomes might also facilitate pu- three chromosomes suggesting rapid changes rifying selection of deleterious