Longitudinal microbial and molecular dynamics in the cystic fibrosis lung after Elexacaftor-Tezacaftor-Ivacaftor therapy.

BACKGROUND: Cystic fibrosis (CF) is a genetic disorder causing poor mucociliary clearance in the airways and subsequent respiratory infection. The recently approved triple therapy Elexacaftor-Tezacaftor-Ivacaftor (ETI) has significantly improved lung function and decreased airway infection in persons with CF (pwCF). This improvement has been shown to occur rapidly, within the first few weeks of treatment. The effects of longer term ETI therapy on lung infection dynamics, however, remain mostly unknown. RESULTS: Here, we applied 16S rRNA gene amplicon sequencing, untargeted metabolomics, and neutral models to high-resolution, longitudinally collected sputum samples from pwCF on ETI therapy (162 samples, 7 patients) and compared to similarly collected data set from pwCF not taking ETI (630 samples, 9 patients). Because ETI reduces sputum production, samples were collected in freezers provided in the subject's homes at least 3 months after first taking ETI, with those on ETI collecting a sample approximately weekly. The lung function (%ppFEV1) of those in our longitudinal cohort significantly improved after ETI (6.91, SD = 7.74), indicating our study cohort was responsive to ETI. The daily variation of alpha- and beta-diversity of both the microbiome and metabolome was higher for those on ETI, reflecting a more dynamic microbial community and chemical environment during treatment. Four of the seven subjects on ETI were persistently infected with Pseudomonas or Burkholderia in their sputum throughout the sampling period while the total bacterial load significantly decreased with time (R = - 0.42, p = 0.01) in only one subject. The microbiome and metabolome dynamics on ETI were personalized, where some subjects had a progressive change with time on therapy, whereas others had no association with time on treatment. To further classify the augmented variance of the CF microbiome under therapy, we fit the microbiome data to a Hubbell neutral dynamics model in a patient-stratified manner and found that the subjects on ETI had better fit to a neutral model. CONCLUSION: This study shows that the longitudinal microbiology and chemistry in airway secretions from subjects on ETI has become more dynamic and neutral and that after the initial improvement in lung function, many are still persistently infected with CF pathogens.

Distinct and Temporally Stable Assembly Mechanisms Shape Bacterial and Fungal Communities in Vineyard Soils.

Microbial communities in agricultural soils are fundamental for plant growth and in vineyard ecosystems contribute to defining regional wine quality. Managing soil microbes towards beneficial outcomes requires knowledge of how community assembly processes vary across taxonomic groups, spatial scales, and through time. However, our understanding of microbial assembly remains limited. To quantify the contributions of stochastic and deterministic processes to bacterial and fungal assembly across spatial scales and through time, we used 16 s rRNA gene and ITS sequencing in the soil of an emblematic wine-growing region of Italy.Combining null- and neutral-modelling, we found that assembly processes were consistent through time, but bacteria and fungi were governed by different processes. At the within-vineyard scale, deterministic selection and homogenising dispersal dominated bacterial assembly, while neither selection nor dispersal had clear influence over fungal assembly. At the among-vineyard scale, the influence of dispersal limitation increased for both taxonomic groups, but its contribution was much larger for fungal communities. These null-model-based inferences were supported by neutral modelling, which estimated a dispersal rate almost two orders-of-magnitude lower for fungi than bacteria.This indicates that while stochastic processes are important for fungal assembly, bacteria were more influenced by deterministic selection imposed by the biotic and/or abiotic environment. Managing microbes in vineyard soils could thus benefit from strategies that account for dispersal limitation of fungi and the importance of environmental conditions for bacteria. Our results are consistent with theoretical expectations whereby larger individual size and smaller populations can lead to higher levels of stochasticity.

Too simple models may predict the island rule for the wrong reasons.

Biddick & Burns (2021) proposed a null/neutral model that reproduces the island rule as a product of random drift. We agree that it is unnecessary to assume adaptive processes driving island dwarfing or gigantism, but several flaws make their approach unrealistic and thus unsuitable as a stochastic model for evolutionary size changes.

Neutral processes and species sorting in benthic microalgal community assembly: effects of tidal resuspension.

Benthic microalgae (BMA) provide vital food resources for heterotrophs and stabilize sediments with their extracellular secretions. A central goal in ecology is to understand how processes such as species interactions and dispersal, contribute to observed patterns of species abundance and distribution. Our objectives were to assess the effects of sediment resuspension on microalgal community structure. We tested whether taxa-abundance distributions could be predicted using neutral community models (NCMs) and also specific hypotheses about passive migration: (i) As migration decreases in sediment patches, BMA α-diversity will decrease, and (ii) As migration decreases, BMA community dissimilarity (ß-diversity) will increase. Co-occurrence indices (checkerboard score and variance ratio) were also computed to test for deterministic factors, such as competition and niche differentiation, in shaping communities. Two intertidal sites (mudflat and sand bar) differing in resuspension regime were sampled throughout the tidal cycle. Fluorometry and denaturing gradient gel electrophoresis were utilized to investigate diatom community structure. Observed taxa-abundances fit those predicted from NCMs reasonably well (R2 of 0.68-0.93), although comparisons of observed local communities to artificial randomly assembled communities rejected the null hypothesis that diatom communities were assembled solely by stochastic processes. No co-occurrence tests indicated a significant role for competitive exclusion or niche partitioning in microalgal community assembly. In general, predictions about relationships between migration and species diversity were supported for local community dynamics. BMA at low tide (lowest migration) exhibited reduced α-diversity as compared to periods of immersion at both mudflat and sand bar sites. ß-diversity was higher during low tide emersion on the mudflat, but did not differ temporally at the sand bar site. In between-site metacommunity comparisons, low- and high-resuspension sites exhibited distinct community compositions while the low-energy mudflats contained higher microalgal biomass and greater α-diversity. To our knowledge this is the first study to test the relevance of neutral processes in structuring marine microalgal communities. Our results demonstrate a prominent role for stochastic factors in structuring local BMA community assembly, although unidentified nonrandom processes also appear to play some role. High passive migration, in particular, appears to help maintain species diversity and structure communities in both sand and muddy habitats.

Metacommunity speciation models and their implications for diversification theory.

The emergence of new frameworks combining evolutionary and ecological dynamics in communities opens new perspectives on the study of speciation. By acknowledging the relative contribution of local and regional dynamics in shaping the complexity of ecological communities, metacommunity theory sheds a new light on the mechanisms underlying the emergence of species. Three integrative frameworks have been proposed, involving neutral dynamics, niche theory, and life history trade-offs respectively. Here, we review these frameworks of metacommunity theory to emphasise that: (1) studies on speciation and community ecology have converged towards similar general principles by acknowledging the central role of dispersal in metacommunities dynamics, (2) considering the conditions of emergence and maintenance of new species in communities has given rise to new models of speciation embedded in the metacommunity theory, (3) studies of diversification have shifted from relating phylogenetic patterns to landscapes spatial and ecological characteristics towards integrative approaches that explicitly consider speciation in a mechanistic ecological framework. We highlight several challenges, in particular the need for a better integration of the eco-evolutionary consequences of dispersal and the need to increase our understanding on the relative rates of evolutionary and ecological changes in communities.

Error catastrophe in populations under similarity-essential recombination.

Organisms are often more likely to exchange genetic information with others that are similar to themselves. One of the most widely accepted mechanisms of RNA virus recombination requires substantial sequence similarity between the parental RNAs and is termed similarity-essential recombination. This mechanism may be considered analogous to assortative mating, an important form of non-random mating that can be found in animals and plants. Here we study the dynamics of haplotype frequencies in populations evolving under similarity-essential recombination. Haplotypes are represented by a genome of B biallelic loci and the Hamming distance between individuals is used as a criterion for recombination. We derive the evolution equations for the haplotype frequencies assuming that recombination does not occur if the genetic distance is larger than a critical value G and that mutation occurs at a rate µ per locus. Additionally, uniform crossover is considered. Although no fitness is directly associated to the haplotypes, we show that frequency-dependent selection emerges dynamically and governs the haplotype distribution. A critical mutation rate µc can be identified as the error threshold transition, beyond which this selective information cannot be stored. For µ<µc the distribution consists of a dominant sequence surrounded by a cloud of closely related sequences, characterizing a quasispecies. For µ>µc the distribution becomes uniform, with all haplotypes having the same frequency. In the case of extreme assortativeness, where individuals only recombine with others identical to themselves (G=0), the error threshold results µc=1/4, independently of the genome size. For weak assortativity (G=B-1)µc=2(-(B+1)) and for the case of no assortativity (G=B) µc=0. We compute the mutation threshold for 0

Longitudinal Microbial and Molecular Dynamics in the Cystic Fibrosis Lung after Elexacaftor-Tezacaftor-Ivacaftor therapy.

Background: Cystic fibrosis (CF) is a genetic disorder causing poor mucociliary clearance in the airways and subsequent respiratory infection. The recently approved triple therapy Elexacaftor-Tezacaftor-Ivacaftor (ETI) has significantly improved the lung function and decreased airway infection of persons with CF (pwCF). This improvement has been shown to occur rapidly, within the first few weeks of treatment. The effects of longer term ETI therapy on lung infection dynamics, however, remains mostly unknown. Results: Here, we applied 16S rRNA gene amplicon sequencing, untargeted metabolomics, and neutral models to high-resolution, longitudinally collected sputum samples from pwCF on ETI therapy (162 samples, 7 patients) and compared to similarly collected data set of CF subjects not taking ETI (630 samples, 9 patients). Because ETI reduces sputum production, samples were collected in freezers provided in the subject's homes at least 3 months after first taking ETI, with those on ETI collecting a sample approximately weekly. The lung function (%ppFEV1) of those in our longitudinal cohort significantly improved after ETI (6.91, SD = 7.74), indicating our study cohort was responsive to ETI. The daily variation of alpha- and beta-diversity of both the microbiome and metabolome was higher for those on ETI, reflecting a more dynamic microbial community and chemical environment during treatment. Four of the seven subjects on ETI were persistently infected with Pseudomonas or Burkholderia in their sputum throughout the sampling period. The microbiome and metabolome dynamics on ETI were personalized, where some subjects had a progressive change with time on therapy, whereas others had no association with time on treatment. To further classify the augmented variance of the CF microbiome under therapy, we fit the microbiome data to a Hubbell neutral dynamics model in a patient-stratified manner and found that the subjects on ETI had better fit to a neutral model. Conclusion: This study shows that the longitudinal microbiology and chemistry in airway secretions from subjects on ETI has become more dynamic and neutral, and that after the initial improvement in lung function, many are still persistently infected with CF pathogens.

Single Seed Microbiota: Assembly and Transmission from Parent Plant to Seedling.

The seed acts as the primary inoculum source for the plant microbiota. Understanding the processes involved in its assembly and dynamics during germination and seedling emergence has the potential to allow for the improvement of crop establishment. Changes in the bacterial community structure were tracked in 1,000 individual seeds that were collected throughout seed developments of beans and radishes. Seeds were associated with a dominant bacterial taxon that represented more than 75% of all reads. The identity of this taxon was highly variable between the plants and within the seeds of the same plant. We identified selection as the main ecological process governing the succession of dominant taxa during seed filling and maturation. In a second step, we evaluated the seedling transmission of seed-borne taxa in 160 individual plants. While the initial bacterial abundance on seeds was not a good predictor of seedling transmission, the identities of the seed-borne taxa modified the phenotypes of seedlings. Overall, this work revealed that individual seeds are colonized by a few bacterial taxa of highly variable identity, which appears to be important for the early stages of plant development. IMPORTANCE Seeds are key components of plant fitness and are central to the sustainability of the agri-food system. Both the seed quality for food consumption and the seed vigor in agricultural settings can be influenced by the seed microbiota. Understanding the ecological processes involved in seed microbiota assembly will inform future practices for promoting the presence of important seed microorganisms for plant health and productivity. Our results highlighted that seeds were associated with one dominant bacterial taxon of variable taxonomic identity. This variety of dominant taxa was due to (i) spatial heterogeneity between and within plants and (ii) primary succession during seed development. According to neutral models, selection was the main driver of microbial community assembly for both plant species.

The Effects of Demography and Genetics on the Neutral Distribution of Quantitative Traits.

Neutral models for quantitative trait evolution are useful for identifying phenotypes under selection. These models often assume normally distributed phenotypes. This assumption may be violated when a trait is affected by relatively few variants or when the effects of those variants arise from skewed or heavy tailed distributions. Molecular phenotypes such as gene expression levels may have these properties. To accommodate deviations from normality, models making fewer assumptions about the underlying genetics and patterns of variation are needed. Here, we develop a general neutral model for quantitative trait variation using a coalescent approach. This model allows interpretation of trait distributions in terms of familiar population genetic parameters because it is based on the coalescent. We show how the normal distribution resulting from the infinitesimal limit, where the number of loci grows large as the effect size per mutation becomes small, depends only on expected pairwise coalescent times. We then demonstrate how deviations from normality depend on demography through the distribution of coalescence times as well as through genetic parameters. In particular, population growth events exacerbate deviations while bottlenecks reduce them. We demonstrate the practical applications of this model by showing how to sample from the neutral distribution of [Formula: see text], the ratio of the variance between subpopulations to that in the overall population. We further show it is likely impossible to distinguish sparsity from skewed or heavy tailed mutational effects using only sampled trait values. The model analyzed here greatly expands the parameter space for neutral trait models.

Methods for detecting non-randomness in species co-occurrences: a contribution.

Comparison of co-occurrences between species on a group of islands with those expected from a randombased null model could provide evidence on community structure. However, it is difficult to decide on the appropriate null model. Gilpin and Diamond proposed a model and a test for departure from it, but this test is shown to indicate significant structure even when applied to a matrix of random numbers. An alternative method is suggested, using the distribution of Gilpin and Diamond's deviation as test statistic, but determining the expected distribution by Monto Carlo simulation, and using many such simulations as a randomisation test of significance. The null model used accepts the observed totals of occurrences for islands and species; it therefore offers a somewhat conservative test. Applied to the Vanuatu bird data that Gilpin and Diamond used, significant departure from a null model is seen, but with an excess of extreme negative associations, the opposite result from that given by Gilpin and Diamond's method. It is not possible to tell whether the negative associations are due to autecology, biogeography, or to interactions between species.

Disturbance, neutral theory, and patterns of beta diversity in soil communities.

Beta diversity describes how local communities within an area or region differ in species composition/abundance. There have been attempts to use changes in beta diversity as a biotic indicator of disturbance, but lack of theory and methodological caveats have hampered progress. We here propose that the neutral theory of biodiversity plus the definition of beta diversity as the total variance of a community matrix provide a suitable, novel, starting point for ecological applications. Observed levels of beta diversity (BD) can be compared to neutral predictions with three possible outcomes: Observed BD equals neutral prediction or is larger (divergence) or smaller (convergence) than the neutral prediction. Disturbance might lead to either divergence or convergence, depending on type and strength. We here apply these ideas to datasets collected on oribatid mites (a key, very diverse soil taxon) under several regimes of disturbances. When disturbance is expected to increase the heterogeneity of soil spatial properties or the sampling strategy encompassed a range of diverging environmental conditions, we observed diverging assemblages. On the contrary, we observed patterns consistent with neutrality when disturbance could determine homogenization of soil properties in space or the sampling strategy encompassed fairly homogeneous areas. With our method, spatial and temporal changes in beta diversity can be directly and easily monitored to detect significant changes in community dynamics, although the method itself cannot inform on underlying mechanisms. However, human-driven disturbances and the spatial scales at which they operate are usually known. In this case, our approach allows the formulation of testable predictions in terms of expected changes in beta diversity, thereby offering a promising monitoring tool.

Comments about some species abundance patterns: classic, neutral, and niche partitioning models / Comentários sobre alguns padrões de espécie-abundância: modelos clássicos, neutros e de partição de nicho

The literature on species abundance models is extensive and a great deal of new and important contributions have been published in the last three decades. Broadly speaking, one can recognize five families of species abundance models: i) purely statistical or classic models (Broken-stick, Log-normal, Logarithmic and Geometric series); ii) branching process (Zipf-Mandelbrot and Fractal branching models); iii) population dynamics (Neutral models included); iv) spatial distribution of individuals (Multifractal and HEAP models) and v) niche partitioning (Sugihara's breakage and Tokeshi models). Among these the neutral, the classic and the niche partitioning models have been the most applied to natural communities, the former having been more extensively discussed than the others in the last years. The objective of this paper is to comment some aspects of the classic, neutral and niche partitioning models in a way that the proposed distributions may contribute to the analysis of the empirical patterns of species abundance. In spite of the variety of models, the distributions in general vary between the log-normal and the logarithmic series. From these models the Power-Fraction, together with independent niche dimensions measures, are amenable to experimental tests and may offer answers on which resources are important in the structuring of biological communities.

A literatura sobre modelos de espécie-abundância é extensa e importantes contribuições têm sido publicadas nas últimas três décadas. De forma geral, são reconhecidos cinco grandes grupos de modelos: i) os que descrevem distribuições puramente estatísticas ou modelos clássicos (Broken-stick, log-normal, série logarítmica e série geométrica); ii) os que simulam processos de ramificação hierárquica (modelos Zipf-Mandelbrot e Fractal); iii) de dinâmica de populações (modelos Neutros); iv) de distribuição espacial de indivíduos (modelos Multifractal e HEAP); e v) de partição de nicho (modelos de Sugihara e de Tokeshi). Os modelos clássicos, os de partição de nicho e principalmente os modelos neutros têm sido os mais utilizados em estudos de comunidades naturais. O objetivo deste artigo é discutir de que forma as distribuições geradas por estes três grupos, bem com as suas bases conceituais, podem contribuir com a análise de padrões empíricos de espécie-abundância. Em geral, estes padrões variam entre as curvas log-normal e série logarítmica. Dentre a variedade de modelos existentes, o Power-fraction possibilita a simulação de uma grande amplitude de padrões de abundância relativa e é de utilização relativamente simples, podendo ser utilizado em testes experimentais de perturbação ou de sucessão ecológica. Aliado a medidas independentes de dimensões de nicho, este modelo pode ainda oferecer respostas sobre quais recursos são essenciais à estruturação de comunidades biológicas.

Comments about some species abundance patterns: classic, neutral, and niche partitioning models

The literature on species abundance models is extensive and a great deal of new and important contributions have been published in the last three decades. Broadly speaking, one can recognize five families of species abundance models: i) purely statistical or classic models (Broken-stick, Log-normal, Logarithmic and Geometric series); ii) branching process (Zipf-Mandelbrot and Fractal branching models); iii) population dynamics (Neutral models included); iv) spatial distribution of individuals (Multifractal and HEAP models) and v) niche partitioning (Sugihara's breakage and Tokeshi models). Among these the neutral, the classic and the niche partitioning models have been the most applied to natural communities, the former having been more extensively discussed than the others in the last years. The objective of this paper is to comment some aspects of the classic, neutral and niche partitioning models in a way that the proposed distributions may contribute to the analysis of the empirical patterns of species abundance. In spite of the variety of models, the distributions in general vary between the log-normal and the logarithmic series. From these models the Power-Fraction, together with independent niche dimensions measures, are amenable to experimental tests and may offer answers on which resources are important in the structuring of biological communities.

A literatura sobre modelos de espécie-abundância é extensa e importantes contribuições têm sido publicadas nas últimas três décadas. De forma geral, são reconhecidos cinco grandes grupos de modelos: i) os que descrevem distribuições puramente estatísticas ou modelos clássicos (Broken-stick, log-normal, série logarítmica e série geométrica); ii) os que simulam processos de ramificação hierárquica (modelos Zipf-Mandelbrot e Fractal); iii) de dinâmica de populações (modelos Neutros); iv) de distribuição espacial de indivíduos (modelos Multifractal e HEAP); e v) de partição de nicho (modelos de Sugihara e de Tokeshi). Os modelos clássicos, os de partição de nicho e principalmente os modelos neutros têm sido os mais utilizados em estudos de comunidades naturais. O objetivo deste artigo é discutir de que forma as distribuições geradas por estes três grupos, bem com as suas bases conceituais, podem contribuir com a análise de padrões empíricos de espécie-abundância. Em geral, estes padrões variam entre as curvas log-normal e série logarítmica. Dentre a variedade de modelos existentes, o Power-fraction possibilita a simulação de uma grande amplitude de padrões de abundância relativa e é de utilização relativamente simples, podendo ser utilizado em testes experimentais de perturbação ou de sucessão ecológica. Aliado a medidas independentes de dimensões de nicho, este modelo pode ainda oferecer respostas sobre quais recursos são essenciais à estruturação de comunidades biológicas.