Dynamics of Genome Rearrangement in Bacterial Populations

Genome structure variation has profound impacts on phenotype in organisms ranging from microbes to humans, yet little is known about how natural selection acts on genome arrangement. Pathogenic bacteria such as Yersinia pestis, which causes bubonic and pneumonic plague, often exhibit a high degree of genomic rearrangement. The recent availability of several Yersinia genomes offers an unprecedented opportunity to study the evolution of genome structure and arrangement. We introduce a set of statistical methods to study patterns of rearrangement in circular chromosomes and apply them to the Yersinia. We constructed a multiple alignment of eight Yersinia genomes using Mauve software to identify 78 conserved segments that are internally free from genome rearrangement. Based on the alignment, we applied Bayesian statistical methods to infer the phylogenetic inversion history of Yersinia. The sampling of genome arrangement reconstructions contains seven parsimonious tree topologies, each having different histories of 79 inversions. Topologies with a greater number of inversions also exist, but were sampled less frequently. The inversion phylogenies agree with results suggested by SNP patterns. We then analyzed reconstructed inversion histories to identify patterns of rearrangement. We confirm an over-representation of “symmetric inversions”—inversions with endpoints that are equally distant from the origin of chromosomal replication. Ancestral genome arrangements demonstrate moderate preference for replichore balance in Yersinia. We found that all inversions are shorter than expected under a neutral model, whereas inversions acting within a single replichore are much shorter than expected. We also found evidence for a canonical configuration of the origin and terminus of replication. Finally, breakpoint reuse analysis reveals that inversions with endpoints proximal to the origin of DNA replication are nearly three times more frequent. Our findings represent the first characterization of genome arrangement evolution in a bacterial population evolving outside laboratory conditions. Insight into the process of genomic rearrangement may further the understanding of pathogen population dynamics and selection on the architecture of circular bacterial chromosomes

Reductive Genome Evolution from the Mother of Rickettsia

The Rickettsia genus is a group of obligate intracellular α-proteobacteria representing a paradigm of reductive evolution. Here, we investigate the evolutionary processes that shaped the genomes of the genus. The reconstruction of ancestral genomes indicates that their last common ancestor contained more genes, but already possessed most traits associated with cellular parasitism. The differences in gene repertoires across modern Rickettsia are mainly the result of differential gene losses from the ancestor. We demonstrate using computer simulation that the propensity of loss was variable across genes during this process. We also analyzed the ratio of nonsynonymous to synonymous changes (Ka/Ks) calculated as an average over large sets of genes to assay the strength of selection acting on the genomes of Rickettsia, Anaplasmataceae, and free-living γ-proteobacteria. As a general trend, Ka/Ks were found to decrease with increasing divergence between genomes. The high Ka/Ks for closely related genomes are probably due to a lag in the removal of slightly deleterious nonsynonymous mutations by natural selection. Interestingly, we also observed a decrease of the rate of gene loss with increasing divergence, suggesting a similar lag in the removal of slightly deleterious pseudogene alleles. For larger divergence (Ks > 0.2), Ka/Ks converge toward similar values indicating that the levels of selection are roughly equivalent between intracellular α-proteobacteria and their free-living relatives. This contrasts with the view that obligate endocellular microorganisms tend to evolve faster as a consequence of reduced effectiveness of selection, and suggests a major role of enhanced background mutation rates on the fast protein divergence in the obligate intracellular α-proteobacteria

Inversion-based genomic signatures

<p>Abstract</p> <p>Background</p> <p>Reconstructing complete ancestral genomes (at least in terms of their gene inventory and arrangement) is attracting much interest due to the rapidly increasing availability of whole genome sequences. While modest successes have been reported for mammalian and even vertebrate genomes, more divergent groups continue to pose a stiff challenge, mostly because current models of genomic evolution support too many choices.</p> <p>Results</p> <p>We describe a novel type of genomic signature based on rearrangements that characterizes evolutionary changes that must be common to all minimal rearrangement scenarios; by focusing on global patterns of rearrangements, such signatures bypass individual variations and sharply restrict the search space. We present the results of extensive simulation studies demonstrating that these signatures can be used to reconstruct accurate ancestral genomes and phylogenies even for widely divergent collections.</p> <p>Conclusion</p> <p>Focusing on genome triples rather than genomes pairs unleashes the full power of evolutionary analysis. Our genomic signature captures shared evolutionary events and thus can form the basis of a robust analysis and reconstruction of evolutionary history.</p

Towards comprehensive understanding of bacterial genetic diversity:large-scale amplifications in Bordetella pertussis and Mycobacterium tuberculosis

Bacterial genetic diversity is often described solely using base-pair changes despite a wide variety of other mutation types likely being major contributors. Tandem duplication/amplifications are thought to be widespread among bacteria but due to their often-intractable size and instability, comprehensive studies of these mutations are rare. We define a methodology to investigate amplifications in bacterial genomes based on read depth of genome sequence data as a proxy for copy number. We demonstrate the approach with Bordetella pertussis , whose insertion sequence element-rich genome provides extensive scope for amplifications to occur. Analysis of data for 2430 B. pertussis isolates identified 272 putative amplifications, of which 94 % were located at 11 hotspot loci. We demonstrate limited phylogenetic connection for the occurrence of amplifications, suggesting unstable and sporadic characteristics. Genome instability was further described in vitro using long-read sequencing via the Nanopore platform, which revealed that clonally derived laboratory cultures produced heterogenous populations rapidly. We extended this research to analyse a population of 1000 isolates of another important pathogen, Mycobacterium tuberculosis . We found 590 amplifications in M. tuberculosis , and like B. pertussis , these occurred primarily at hotspots. Genes amplified in B. pertussis include those involved in motility and respiration, whilst in M. tuberuclosis, functions included intracellular growth and regulation of virulence. Using publicly available short-read data we predicted previously unrecognized, large amplifications in B. pertussis and M. tuberculosis . This reveals the unrecognized and dynamic genetic diversity of B. pertussis and M. tuberculosis , highlighting the need for a more holistic understanding of bacterial genetics

Sorting by weighted inversions considering length and symmetry

International audienceLarge-scale mutational events that occur when stretches of DNA sequence move throughout genomes are called genome rearrangements. In bacteria, inversions are one of the most frequently observed rearrangements. In some bacterial families, inversions are biased in favor of symmetry as shown by recent research. In addition, several results suggest that short segment inversions are more frequent in the evolution of microbial genomes. Despite the fact that symmetry and length of the reversed segments seem very important, they have not been considered together in any problem in the genome rearrangement field. Here, we define the problem of sorting genomes (or permutations) using inversions whose costs are assigned based on their lengths and asymmetries. We consider two formulations of the same problem depending on whether we know the orientation of the genes. Several procedures are presented and we assess these procedure performances on a large set of more than 4.4 × 10^9 permutations. The ideas presented in this paper provide insights to solve the problem and set the stage for a proper theoretical analysis

SoRT2: a tool for sorting genomes and reconstructing phylogenetic trees by reversals, generalized transpositions and translocations

SoRT2 is a web server that allows the user to perform genome rearrangement analysis involving reversals, generalized transpositions and translocations (including fusions and fissions), and infer phylogenetic trees of genomes being considered based on their pairwise genome rearrangement distances. It takes as input two or more linear/circular multi-chromosomal gene (or synteny block) orders in FASTA-like format. When the input is two genomes, SoRT2 will quickly calculate their rearrangement distance, as well as a corresponding optimal scenario by highlighting the genes involved in each rearrangement operation. In the case of multiple genomes, SoRT2 will also construct phylogenetic trees of these genomes based on a matrix of their pairwise rearrangement distances using distance-based approaches, such as neighbor-joining (NJ), unweighted pair group method with arithmetic mean (UPGMA) and Fitch–Margoliash (FM) methods. In addition, if the function of computing jackknife support values is selected, SoRT2 will further perform the jackknife analysis to evaluate statistical reliability of the constructed NJ, UPGMA and FM trees. SoRT2 is available online at http://bioalgorithm.life.nctu.edu.tw/SORT2/