Predator-by-Environment Interactions Mediate Bacterial Competition in the \u3ci\u3eDictyostelium discoideum\u3c/i\u3e Microbiome

Interactions between species and their environment play a key role in the evolution of diverse communities, and numerous studies have emphasized that interactions among microbes and among trophic levels play an important role in maintaining microbial diversity and ecosystem functioning. In this study, we investigate how two of these types of interactions, public goods cooperation through the production of iron scavenging siderophores and predation by the social amoeba Dictyostelium discoideum, mediate competition between two strains of Pseudomonas fluorescens that were co-isolated from D. discoideum. We find that although we are able to generally predict the competitive outcomes between strains based on the presence and absence of either D. discoideum or iron, predator-by-environment interactions result in unexpected competitive outcomes. This suggests that while both cooperation and predation can mediate the competitive abilities and potentially the coexistence of these strains, predicting how combinations of different environments affect even the relatively simple microbiome of D. discoideum remains challenging

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Spite and the scale of competition in Pseudomonas aeruginosa

This work was funded by the European Research Council and the Leverhulme Trust (A.B.), the Natural Environment Research Council (R.F.I. and A.B.), and Balliol College and the Royal Society (A.G.).Scale of competition has been shown to be an important factor in shaping the evolution of social interactions. Although many theoretical and experimental studies have examined its effect on altruistic cooperation, relatively little research effort has been focused on spiteful behaviors-actions that harm both the actor and the recipient. In this study, we expand on existing theory by investigating the importance of the global frequency of spiteful alleles, and we determine experimentally how the scale of competition affects selection for spite in the bacterial pathogen Pseudomonas aeruginosa under high and intermediate spatial relatedness. Consistent with our theoretical results, we found in our experiments that spiteful genotypes are more favored under local (rather than global) competition and intermediate (rather than high) spatial relatedness, conditions that have been shown to select against indiscriminate altruism.Publisher PDFPeer reviewe

The evolutionary ecology of spiteful bacteriocin production

Understanding the conditions that favour the evolution and maintenance of spiteful bacteriocin production combines two important questions from the fields of social evolution and microbiology. Spiteful behaviours, though, initially thought to be rare represent an important class of interactions between bacteria through the production of bacteriocins. Bacteriocins can be considered spiteful as they are costly to produce (in many cases requiring lysis) and are costly to sensitive bacteria (i.e. they are lethal). However, much about the ecology of spiteful behaviours and bacteriocin production remains unclear. Mathematical models have given us important insights into some conditions that should favour bacteriocin production, but few empirical studies exist supporting these results. In this thesis I use the bacterium Pseudomonas aeruginosa (a prolific producer of bacteriocins), to examine conditions that favour bacteriocin production. I also investigate more specific elements about this system and toxin production in general. I find that bacteriocin production in P. aeruginosa closely follows predictions made from mathematical models under a range of different conditions (e.g. frequency, scale of competition, multiple social traits). I also find that resistance can evolve to bacteriocins and biological mechanisms such as the neutralisation of one’s own toxin can have important consequences. Finally, I consider bacteriocin as a policing trait testing predictions about the role that linkage plays in policing. This work represents a comprehensive study into the importance of bacteriocin production in bacteria

A Longitudinal Study of Academic Web Links: Identifying and Explaining Change

A thesis submitted in partial fulfilment of the requirements of the University of Wolverhampton for the degree of Doctor of PhilosophyA problem common to all current web link analyses is that, as the web is continuously evolving, any web-based study may be out of date by the time it is published in academic literature. It is therefore important to know how web link analyses results vary over time, with a low rate of variation lengthening the amount of time corresponding to a tolerable loss in quality. Moreover, given the lack of research on how academic web spaces change over time, from an information science perspective it would interesting to see what patterns and trends could be identified by longitudinal research and the study of university web links seems to provide a convenient means by which to do so. The aim of this research is to identify and track changes in three academic webs (UK, Australia and New Zealand) over time, tracking various aspects of academic webs including site size and overall linking characteristics, and to provide theoretical explanations of the changes found. This should therefore provide some insight into the stability of previous and future webometric analyses. Alternative Document Models (ADMs), created with the purpose of reducing the extent to which anomalies occur in counts of web links at the page level, have been used extensively within webometrics as an alternative to using the web page as the basic unit of analysis. This research carries out a longitudinal study of ADMs in an attempt to ascertain which model gives the most consistent results when applied to the UK, Australia and New Zealand academic web spaces over the last six years. The results show that the domain ADM gives the most consistent results with the directory ADM also giving more reliable results than are evident when using the standard page model. Aggregating at the site (or university) level appears to provide less consistent results than using the page as the standard unit of measure, and this finding holds true over all three academic webs and for each time period examined over the last six years. The question of whether university web sites publish the same kind of information and use the same kind of hyperlinks year on year is important from the perspective of interpreting the results of academic link analyses, because changes in link types over time would also force interpretations of link analyses to change over time. This research uses a link classification exercise to identify temporal changes in the distribution of different types of academic web links, using three academic web spaces in the years 2000 and 2006. Significant increases in ‘research oriented’, ‘social/leisure’ and ‘superficial’ links were identified as well as notable decreases in the ‘technical’ and ‘personal’ links. Some of these changes identified may be explained by general changes in the management of university web sites and some by more wide-spread Internet trends, e.g., dynamic pages, blogs and social networking. The increase in the proportion of research-oriented links is particularly hopeful for future link analysis research. Identifying quantitative trends in the UK, Australian and New Zealand academic webs from 2000 to 2005 revealed that the number of static pages and links in each of the three academic webs appears to have stabilised as far back as 2001. This stabilisation may be partly due to an increase in dynamic pages which are normally excluded from webometric analyses. In response to the problem for webometricians due to the constantly changing nature of the Internet, the results presented here are encouraging evidence that webometrics for academic spaces may have a longer-term validity than would have been previously assumed. The relationship between university inlinks and research activity indicators over time was examined, as well as the reasons for individual universities experiencing significant increases and decreases in inlinks over the last six years. The findings indicate that between 66% and 70% of outlinks remain the same year on year for all three academic web spaces, although this stability conceals large individual differences. Moreover, there is evidence of a level of stability over time for university site inlinks when measured against research. Surprisingly however, inlink counts can vary significantly from year to year for individual universities, for reasons unrelated to research, underlining that webometric results should be interpreted cautiously at the level of individual universities. Therefore, on average since 2001 the university web sites of the UK, Australia and New Zealand have been relatively stable in terms of size and linking patterns, although this hides a constant renewing of old pages and areas of the sites. In addition, the proportion of research-related links seems to be slightly increasing. Whilst the former suggests that webometric results are likely to have a surprisingly long shelf-life, perhaps closer to five years than one year, the latter suggests that webometrics is going to be increasingly useful as a tool to track research online. While there have already been many studies involving academic webs spaces, and much work has been carried out on the web from a longitudinal perspective, this thesis concentrates on filling a critical gap in current webometric research by combining the two and undertaking a longitudinal study of academic webs. In comparison with previous web-related longitudinal studies this thesis makes a number of novel contributions. Some of these stem from extending established webometric results, either by introducing a longitudinal aspect (looking at how various academic web metrics such as research activity indicators, site size or inlinks change over time) or by their application to other countries. Other contributions are made by combining traditional webometric methods (e.g. combining topical link classification exercises with longitudinal study) or by identifying and examining new areas for research (for example, dynamic pages and non-HTML documents). No previous web-based longitudinal studies have focused on academic links and so the main findings that (for UK, Australian and New Zealand academic webs between 2000 and 2006) certain academic link types exhibit changing patterns over time, approximately two-thirds of outlinks remain the same year on year and the number of static pages and links appears to have stabilised are both significant and novel

Data from: An experimental study of strong reciprocity in bacteria

Strong reciprocity, whereby cooperators punish non-cooperators, may help to explain the evolutionary success of cooperative behaviours. However, theory suggests that selection for strong reciprocity can depend upon tight genetic linkage between cooperation and punishment, to avoid the strategy being outcompeted by non-punishing cooperators. We tested this hypothesis using experimental populations of the bacterium Pseudomonas aeruginosa, which cooperate by producing iron-scavenging siderophores and, in this context, punish non-cooperators with toxins. Consistent with theory, we show that cooperative punishers can indeed invade cheats, but only when the traits are tightly linked. These results emphasize that punishment is only likely to be favoured when the punishment itself leads to a direct or indirect fitness benefit to the actor

Cheating fosters species co-existence in well-mixed bacterial communities

Explaining the enormous biodiversity observed in bacterial communities is challenging because ecological theory predicts that competition between species occupying the same niche should lead to the exclusion of less competitive community members. Competitive exclusion should be particularly strong when species compete for a single limiting resource or live in unstructured habitats that offer no refuge for weaker competitors. Here, we describe the ‘cheating effect’, a form of intra-specific competition that can counterbalance between-species competition, thereby fostering biodiversity in unstructured habitats. Using experimental communities consisting of the strong competitor Pseudomonas aeruginosa (PA) and its weaker counterpart Burkholderia cenocepacia (BC), we show that co-existence is impossible when the two species compete for a single limiting resource, iron. However, when introducing a PA cheating mutant, which specifically exploits the iron scavenging siderophores produced by the PA wild type, we found that biodiversity was preserved under well-mixed conditions where PA cheats could outcompete the PA wild type. Cheating fosters biodiversity in our system because it creates strong intra-specific competition, which equalises fitness differences between PA and BC. Our study identifies cheating – typically considered a destructive element – as a constructive force in shaping biodiversity

Data from: Spite versus cheats: competition among social strategies shapes virulence in Pseudomonas aeruginosa

Social interactions have been shown to play an important role in bacterial evolution and virulence. The majority of empirical studies conducted have only considered social traits in isolation, yet numerous social traits, such as the production of spiteful bacteriocins (anti-competitor toxins) and iron-scavenging siderophores (a public good) by the opportunistic pathogen Pseudomonas aeruginosa, are frequently expressed simultaneously. Crucially, both bacteriocin production and siderophore cheating can be favoured under the same competitive conditions, and we develop theory and carry out experiments to determine how the success of a bacteriocin-producing genotype is influenced by social cheating of susceptible competitors and the resultant impact on disease severity (virulence). Consistent with our theoretical predictions, we find that the spiteful genotype is favoured at higher local frequencies when competing against public good cheats. Furthermore, the relationship between spite frequency and virulence is significantly altered when the spiteful genotype is competed against cheats compared with cooperators. These results confirm the ecological and evolutionary importance of considering multiple social traits simultaneously. Moreover, our results are consistent with recent theory regarding the invasion conditions for strong reciprocity (helping cooperators and harming non-cooperators)

Presence of a Loner Strain Maintains Cooperation and Diversity in Well-Mixed Bacterial Communities

Cooperation and diversity abound in nature despite cooperators risking exploitation from defectors and superior competitors displacing weaker ones. Understanding the persistence of cooperation and diversity is therefore a major problem for evolutionary ecology, especially in the context of well-mixed populations, where the potential for exploitation and displacement is greatest. Here, we demonstrate that a ‘loner effect’, described by economic game theorists, can maintain cooperation and diversity in real-world biological settings. We use mathematical models of public-good-producing bacteria to show that the presence of a loner strain, which produces an independent but relatively inefficient good, can lead to rock–paper–scissor dynamics, whereby cooperators outcompete loners, defectors outcompete cooperators and loners outcompete defectors. These model predictions are supported by our observations of evolutionary dynamics in well-mixed experimental communities of the bacterium Pseudomonas aeruginosa. We find that the coexistence of cooperators and defectors that produce and exploit, respectively, the iron-scavenging siderophore pyoverdine, is stabilized by the presence of loners with an independent iron-uptake mechanism. Our results establish the loner effect as a simple and general driver of cooperation and diversity in environments that would otherwise favour defection and the erosion of diversity