Genome hyperevolution and the success of a parasite

The strategy of antigenic variation is to present a constantly changing population phenotype that enhances parasite transmission, through evasion of immunity arising within, or existing between, host animals. Trypanosome antigenic variation occurs through spontaneous switching among members of a silent archive of many hundreds of variant surface glycoprotein (VSG) antigen genes. As with such contingency systems in other pathogens, switching appears to be triggered through inherently unstable DNA sequences. The archive occupies subtelomeres, a genome partition that promotes hypermutagenesis and, through telomere position effects, singular expression of VSG. Trypanosome antigenic variation is augmented greatly by the formation of mosaic genes from segments of pseudo-VSG, an example of implicit genetic information. Hypermutation occurs apparently evenly across the whole archive, without direct selection on individual VSG, demonstrating second-order selection of the underlying mechanisms. Coordination of antigenic variation, and thereby transmission, occurs through networking of trypanosome traits expressed at different scales from molecules to host populations

Variable plasmid fitness effects and mobile genetic element dynamics across Pseudomonas species

Mobile genetic elements (MGE) such as plasmids and transposons mobilise genes within and between species, playing a crucial role in bacterial evolution via horizontal gene transfer (HGT). Currently we lack data on variation in MGE dynamics across bacterial host species. We tracked the dynamics of a large conjugative plasmid, pQBR103, and its Tn5042 mercury resistance transposon, in five diverse Pseudomonas species in environments with and without mercury selection. Plasmid fitness effects and stability varied extensively between host species and environments, as did the propensity for chromosomal capture of the Tn5042 mercury resistance transposon associated with loss of the plasmid. Whereas P. fluorescens and P. savastanoi stably maintained the plasmid in both environments, the plasmid was highly unstable in P. aeruginosa and P. putida, where plasmid-free genotypes with Tn5042 captured to the chromosome invaded to higher frequency under mercury selection. These data confirm that plasmid stability is dependent upon the specific genetic interaction of the plasmid and host chromosome rather than being a property of plasmids alone, and moreover imply that MGE dynamics in diverse natural communities are likely to be complex and driven by a subset of species capable of stably maintaining plasmids which would then act as hubs of HGT

Migration promotes plasmid stability under spatially heterogeneous positive selection

Bacteria-plasmid associations can be mutualistic or antagonistic depending on the strength of positive selection for plasmid-encoded genes, with contrasting outcomes for plasmid stability. In mutualistic environments, plasmids are swept to high frequency by positive selection, increasing the likelihood of compensatory evolution to ameliorate the plasmid cost, which promotes long-term stability. In antagonistic environments, plasmids are purged by negative selection, reducing the probability of compensatory evolution and driving their extinction. Here we show, using experimental evolution of Pseudomonas fluorescens and the mercury-resistance plasmid, pQBR103, that migration promotes plasmid stability in spatially heterogeneous selection environments. Specifically, migration from mutualistic environments, by increasing both the frequency of the plasmid and the supply of compensatory mutations, stabilized plasmids in antagonistic environments where, without migration, they approached extinction. These data suggest that spatially heterogeneous positive selection, which is common in natural environments, coupled with migration helps to explain the stability of plasmids and the ecologically important genes that they encode

The evolution of plasmid stability: Are infectious transmission and compensatory evolution competing evolutionary trajectories?

Conjugative plasmids are widespread and play an important role in bacterial evolution by accelerating adaptation through horizontal gene transfer. However, explaining the long-term stability of plasmids remains challenging because segregational loss and the costs of plasmid carriage should drive the loss of plasmids though purifying selection. Theoretical and experimental studies suggest two key evolutionary routes to plasmid stability: First, the evolution of high conjugation rates would allow plasmids to survive through horizontal transmission as infectious agents, and second, compensatory evolution to ameliorate the cost of plasmid carriage can weaken purifying selection against plasmids. How these two evolutionary strategies for plasmid stability interact is unclear. Here, we summarise the literature on the evolution of plasmid stability and then use individual based modelling to investigate the evolutionary interplay between the evolution of plasmid conjugation rate and cost amelioration. We find that, individually, both strategies promote plasmid stability, and that they act together to increase the likelihood of plasmid survival. However, due to the inherent costs of increasing conjugation rate, particularly where conjugation is unlikely to be successful, our model predicts that amelioration is the more likely long-term solution to evolving stable bacteria-plasmid associations. Our model therefore suggests that bacteria-plasmid relationships should evolve towards lower plasmid costs that may forestall the evolution of highly conjugative, 'infectious' plasmids

Extremely fast amelioration of plasmid fitness costs by multiple functionally diverse pathways

The acquisition of plasmids is often accompanied by fitness costs such that compensatory evolution is required to allow plasmid survival, but it is unclear whether compensatory evolution can be extensive or rapid enough to maintain plasmids when they are very costly. The mercury-resistance plasmid pQBR55 drastically reduced the growth of its host, Pseudomonas fluorescens SBW25, immediately after acquisition, causing a small colony phenotype. However, within 48 h of growth on agar plates we observed restoration of the ancestral large colony morphology, suggesting that compensatory mutations had occurred. Relative fitness of these evolved strains, in lab media and in soil microcosms, varied between replicates, indicating different mutational mechanisms. Using genome sequencing we identified that restoration was associated with chromosomal mutations in either a hypothetical DNA-binding protein PFLU4242, RNA polymerase or the GacA/S two-component system. Targeted deletions in PFLU4242, gacA or gacS recapitulated the ameliorated phenotype upon plasmid acquisition, indicating three distinct mutational pathways to compensation. Our data shows that plasmid compensatory evolution is fast enough to allow survival of a plasmid despite it imposing very high fitness costs upon its host, and indeed may regularly occur during the process of isolating and selecting individual plasmid-containing clones

The ecology and evolution of pangenomes

Since the first genome-scale comparisons, it has been evident that the genomes of many species are unbound by strict vertical descent: Large differences in gene content can occur among genomes belonging to the same prokaryotic species, with only a fraction of genes being universal to all genomes. These insights gave rise to the pangenome concept. The pangenome is defined as the set of all the genes present in a given species and can be subdivided into the accessory genome, present in only some of the genomes, and the core genome, present in all the genomes. Pangenomes arise due to gene gain by genomes from other species through horizontal gene transfer and differential gene loss among genomes, and have been described in both prokaryotes and eukaryotes. Our current view of pangenome variation is phenomenological and incomplete. In this review, we outline the mechanistic, ecological and evolutionary drivers of and barriers to horizontal gene transfer that are likely to structure pangenomes. We highlight the key role of conflict between the host chromosome(s) and the mobile genetic elements that mediate gene exchange. We identify shortcomings in our current models of pangenome evolution and suggest directions for future research to allow a more complete understanding of how and why pangenomes evolve

Positive selection inhibits plasmid coexistence in bacterial genomes

Plasmids play an important role in bacterial evolution by transferring niche-adaptive functional genes between lineages, thus driving genomic diversification. Bacterial genomes commonly contain multiple, coexisting plasmid replicons, which could fuel adaptation by increasing the range of gene functions available to selection and allowing their recombination. However, plasmid coexistence is difficult to explain because the acquisition of plasmids typically incurs high fitness costs for the host cell. Here, we show that plasmid coexistence was stably maintained without positive selection for plasmid-borne gene functions and was associated with compensatory evolution to reduce fitness costs. In contrast, with positive selection, plasmid coexistence was unstable despite compensatory evolution. Positive selection discriminated between differential fitness benefits of functionally redundant plasmid replicons, retaining only the more beneficial plasmid. These data suggest that while the efficiency of negative selection against plasmid fitness costs declines over time due to compensatory evolution, positive selection to maximize plasmid-derived fitness benefits remains efficient. Our findings help to explain the forces structuring bacterial genomes: coexistence of multiple plasmids in a genome is likely to require either rare positive selection in nature or nonredundancy of accessory gene functions among the coexisting plasmids

Spinor condensates and light scattering from Bose-Einstein condensates

These notes discuss two aspects of the physics of atomic Bose-Einstein condensates: optical properties and spinor condensates. The first topic includes light scattering experiments which probe the excitations of a condensate in both the free-particle and phonon regime. At higher light intensity, a new form of superradiance and phase-coherent matter wave amplification were observed. We also discuss properties of spinor condensates and describe studies of ground--state spin domain structures and dynamical studies which revealed metastable excited states and quantum tunneling.Comment: 58 pages, 33 figures, to appear in Proceedings of Les Houches 1999 Summer School, Session LXXI

Plasmids manipulate bacterial behaviour through translational regulatory crosstalk

Beyond their role in horizontal gene transfer, conjugative plasmids commonly encode homologues of bacterial regulators. Known plasmid regulator homologues have highly targeted effects upon the transcription of specific bacterial traits. Here, we characterise a plasmid translational regulator, RsmQ, capable of taking global regulatory control in Pseudomonas fluorescens and causing a behavioural switch from motile to sessile lifestyle. RsmQ acts as a global regulator, controlling the host proteome through direct interaction with host mRNAs and interference with the host’s translational regulatory network. This mRNA interference leads to large-scale proteomic changes in metabolic genes, key regulators, and genes involved in chemotaxis, thus controlling bacterial metabolism and motility. Moreover, comparative analyses found RsmQ to be encoded on a large number of divergent plasmids isolated from multiple bacterial host taxa, suggesting the widespread importance of RsmQ for manipulating bacterial behaviour across clinical, environmental, and agricultural niches. RsmQ is a widespread plasmid global translational regulator primarily evolved for host chromosomal control to manipulate bacterial behaviour and lifestyle