Trajectories of Aging: How Systems Biology in Yeast Can Illuminate Mechanisms of Personalized Aging

All organisms age, but the extent to which all organisms age the same way remains a fundamental unanswered question in biology. Across species, it is now clear that at least some aspects of aging are highly conserved and are perhaps universal, but other mechanisms of aging are private to individual species or sets of closely related species. Within the same species, however, it has generally been assumed that the molecular mechanisms of aging are largely invariant from one individual to the next. With the development of new tools for studying aging at the individual cell level in budding yeast, recent data has called this assumption into question. There is emerging evidence that individual yeast mother cells may undergo fundamentally different trajectories of aging. Individual trajectories of aging are difficult to study by traditional population level assays, but through the application of systems biology approaches combined with novel microfluidic technologies, it is now possible to observe and study these phenomena in real time. Understanding the spectrum of mechanisms that determine how different individuals age is a necessary step toward the goal of personalized geroscience, where healthy longevity is optimized for each individual.     

Slight differences among individuals and the unified neutral theory of biodiversity

The unified neutral theory of biodiversity provides a very simple and counterintuitive explanation of species diversity patterns. By specifying speciation, community size and dispersal, and completely ignoring differences among individual organisms and species, it generates biodiversity patterns that remarkably resemble natural ones. Here I show that adding even slight differences among organisms generates very different patterns and predictions. In large communities with widespread dispersal, heritable differences in viability among individual organisms lead to biodiversity patterns characterised by the overdominance of a single species comprising organisms with relatively high fitness. In communities with local dispersal, the same differences produce rapid community extinction. I conclude that the unified neutral theory is not robust to slight deviations from its most controversial assumption.     

How cells coordinate growth and division

Size is a fundamental attribute impacting cellular design, fitness, and function. Size homeostasis requires a doubling of cell mass with each division. In yeast, division is delayed until a critical size has been achieved. In metazoans, cell cycles can be actively coupled to growth, but in certain cell types extracellular signals may independently induce growth and division. Despite a long history of study, the fascinating mechanisms that control cell size have resisted molecular genetic insight. Recently, genetic screens in Drosophila and functional genomics approaches in yeast have macheted into the thicket of cell size control.     

Relationships between ecological interaction modifications and diffuse coevolution: similarities, differences, and causal links

A major empirical approach in community ecology is to describe the dynamics of a community by examining small subsets of species. Unfortunately, interaction modifications, which cause pair-wise interaction coefficients to depend on the presence or absence of additional species, can make it difficult to predict the overall dynamics of species within a community from experiments with pairs of species. In a similar fashion, one of the major approaches in evolutionary ecology has been to describe the likely evolutionary dynamics of a single species by focusing on the selection imposed by a limited number of other species within the community. However, recent work on diffuse coevolution indicates that selection pressures due to one species can change in the presence of other species. The magnitude of the difficulty that interaction modifications and diffuse coevolution present for predicting ecological and evolutionary dynamics is an unresolved question. Here we outline the similarities and differences between the two topics, discuss experimental and statistical approaches to studying them, and make predictions about when ecological interaction modifications are likely to cause diffuse coevolution. Since the currencies for interaction modifications are usually fitness components such as growth, fecundity, or survival, is it likely that these will translate into corresponding differences in the relative fitness of individuals or genotypes, and thus in general these two phenomena will occur together. We argue that community ecologists and evolutionary ecologists will both benefit from experiments that test for the effects of interaction modifications, and that studies of the mechanisms driving interaction modifications and diffuse coevolution (e.g., changes in behavior, nonlinear effects on shared resources, genetic covariances) will aid our progress in understanding the ecological and evolutionary dynamics of communities.     

Quasi-programmed aging of budding yeast: a trade-off between programmed processes of cell proliferation,differentiation, stress response,survival and death defines yeast lifespan

Recent findings suggest that evolutionarily distant organisms share the key features of the aging process and exhibit similar mechanisms of its modulation by certain genetic, dietary and pharmacological interventions. The scope of this review is to analyze mechanisms that in the yeast Saccharomyces cerevisiae underlie: (1) the replicative and chronological modes of aging; (2) the convergence of these 2 modes of aging into a single aging process; (3) a programmed differentiation of aging cell communities in liquid media and on solid surfaces; and (4) longevity-defining responses of cells to some chemical compounds released to an ecosystem by other organisms populating it. Based on such analysis, we conclude that all these mechanisms are programs for upholding the long-term survival of the entire yeast population inhabiting an ecological niche; however, none of these mechanisms is a ?program of aging? - i.e., a program for progressing through consecutive steps of the aging process.     

Movement‐mediated community assembly and coexistence

Organismal movement is ubiquitous and facilitates important ecological mechanisms that drive community and metacommunity composition and hence biodiversity. In most existing ecological theories and models in biodiversity research, movement is represented simplistically, ignoring the behavioural basis of movement and consequently the variation in behaviour at species and individual levels. However, as human endeavours modify climate and land use, the behavioural processes of organisms in response to these changes, including movement, become critical to understanding the resulting biodiversity loss. Here, we draw together research from different subdisciplines in ecology to understand the impact of individual‐level movement processes on community‐level patterns in species composition and coexistence. We join the movement ecology framework with the key concepts from metacommunity theory, community assembly and modern coexistence theory using the idea of micro–macro links, where various aspects of emergent movement behaviour scale up to local and regional patterns in species mobility and mobile‐link‐generated patterns in abiotic and biotic environmental conditions. These in turn influence both individual movement and, at ecological timescales, mechanisms such as dispersal limitation, environmental filtering, and niche partitioning. We conclude by highlighting challenges to and promising future avenues for data generation, data analysis and complementary modelling approaches and provide a brief outlook on how a new behaviour‐based view on movement becomes important in understanding the responses of communities under ongoing environmental change.     

Functional group diversity, resource preemption and the genesis of invasion resistance in a community of marine algae

Although many studies have investigated how community characteristics such as diversity and disturbance relate to invasibility, the mechanisms underlying biotic resistance to introduced species are not well understood. I manipulated the functional group composition of native algal communities and invaded them with the introduced, Japanese seaweed Sargassum muticum to understand how individual functional groups contributed to overall invasion resistance. The results suggested that space preemption by crustose and turfy algae inhibited S. muticum recruitment and that light preemption by canopy and understory algae reduced S. muticum survivorship. However, other mechanisms I did not investigate could have contributed to these two results. In this marine community the sequential preemption of key resources by different functional groups in different stages of the invasion generated resistance to invasion by S. muticum . Rather than acting collectively on a single resource the functional groups in this system were important for preempting either space or light, but not both resources. My experiment has important implications for diversity–invasibility studies, which typically look for an effect of diversity on individual resources. Overall invasion resistance will be due to the additive effects of individual functional groups (or species) summed over an invader's life cycle. Therefore, the cumulative effect of multiple functional groups (or species) acting on multiple resources is an alternative mechanism that could generate negative relationships between diversity and invasibility in a variety of biological systems.     

Unifying ecology and macroevolution with individual‐based theory

A contemporary goal in both ecology and evolutionary biology is to develop theory that transcends the boundary between the two disciplines, to understand phenomena that cannot be explained by either field in isolation. This is challenging because macroevolution typically uses lineage‐based models, whereas ecology often focuses on individual organisms. Here, we develop a new parsimonious individual‐based theory by adding mild selection to the neutral theory of biodiversity. We show that this model generates realistic phylogenies showing a slowdown in diversification and also improves on the ecological predictions of neutral theory by explaining the occurrence of very common species. Moreover, we find the distribution of individual fitness changes over time, with average fitness increasing at a pace that depends positively on community size. Consequently, large communities tend to produce fitter species than smaller communities. These findings have broad implications beyond biodiversity theory, potentially impacting, for example, invasion biology and paleontology.     

The Gut Microbial Community of Midas Cichlid Fish in Repeatedly Evolved Limnetic-Benthic Species Pairs

Gut bacterial communities are now known to influence a range of fitness related aspects of organisms. But how different the microbial community is in closely related species, and if these differences can be interpreted as adaptive is still unclear. In this study we compared microbial communities in two sets of closely related sympatric crater lake cichlid fish species pairs that show similar adaptations along the limnetic-benthic axis. The gut microbial community composition differs in the species pair inhabiting the older of two crater lakes. One major difference, relative to other fish, is that in these cichlids that live in hypersaline crater lakes, the microbial community is largely made up of Oceanospirillales (52.28%) which are halotolerant or halophilic bacteria. This analysis opens up further avenues to identify candidate symbiotic or co-evolved bacteria playing a role in adaptation to similar diets and life-styles or even have a role in speciation. Future functional and phylosymbiotic analyses might help to address these issues.     

Stochastic association of neighboring replicons creates replication factories in budding yeast

Inside the nucleus, DNA replication is organized at discrete sites called replication factories, consisting of DNA polymerases and other replication proteins. Replication factories play important roles in coordinating replication and in responding to replication stress. However, it remains unknown how replicons are organized for processing at each replication factory. Here we address this question using budding yeast. We analyze how individual replicons dynamically organized a replication factory using live-cell imaging and investigate how replication factories were structured using super-resolution microscopy. Surprisingly, we show that the grouping of replicons within factories is highly variable from cell to cell. Once associated, however, replicons stay together relatively stably to maintain replication factories. We derive a coherent genome-wide mathematical model showing how neighboring replicons became associated stochastically to form replication factories, which was validated by independent microscopy-based analyses. This study not only reveals the fundamental principles promoting replication factory organization in budding yeast, but also provides insight into general mechanisms by which chromosomes organize sub-nuclear structures.     

Fungal diversity from communities to genes

Fungi are hyperdiverse organisms and assemble in complex communities, characterized by high levels of species richness, turnover, and endemism. However, the origins and maintenance of such high diversity and the role environments play in fungal adaptation are still elusive. Traditionally, efforts to understand fungal diversity in their environment have been divided between studies at the species level and below species level, with separate disciplines such as community ecology and population genetics working independently and with little communication. Here I argue that linking these different approaches is required to fully document the diversity of fungi in nature. Understanding the patterns and mechanisms of fungal diversity and composition requires not only the study of species assemblies and ranges, but also relies on comprehending fungal intra-specific variation, dispersal and establishment, including identifying key traits influencing fitness. This implies better integration and cross-fertilization between disciplines addressing fungi at a multitude of biological levels, ranging from genes to whole communities. Such approach will yield direct links between variation, adaptation and environments and provide a much more comprehensive understanding of fungal diversity.     

A minimum stochastic model evaluating the interplay between population density and drift for species coexistence

Despite the general acknowledgment of the role of niche and stochastic process in community dynamics, the role of species relative abundances according to both perspectives may have different effects regarding coexistence patterns. In this study, we explore a minimum probabilistic stochastic model to determine the relationship of populations relative and total abundances with species chances to outcompete each other and their persistence in time (i.e., unstable coexistence). Our model is focused on the effects drift (i.e., random sampling of recruitment) under different scenarios of selection (i.e., fitness differences between species). Our results show that taking into account the stochasticity in demographic properties and conservation of individuals in closed communities (zero-sum assumption), initial population abundance can strongly influence species chances to outcompete each other, despite fitness inequalities between populations, and also, influence the period of coexistence of these species in a particular time interval. Systems carrying capacity can have an important role in species coexistence by exacerbating fitness inequalities and affecting the size of the period of coexistence. Overall, the simple stochastic formulation used in this study demonstrated that populations initial abundances could act as an equalizing mechanism, reducing fitness inequalities, which can favor species coexistence and even make less fitted species to be more likely to outcompete better-fitted species, and thus to dominate ecological communities in the absence of niche mechanisms. Although our model is restricted to a pair of interacting species, and overall conclusions are already predicted by the Neutral Theory of Biodiversity, our main objective was to derive a model that can explicitly show the functional relationship between population densities and community mono-dominance odds. Overall, our study provides a straightforward understanding of how a stochastic process (i.e., drift) may affect the expected outcome based on species selection (i.e., fitness inequalities among species) and the resulting outcome regarding unstable coexistence among species.     

Partitioning the effects of species loss on community variability using multi‐level selection theory

The temporal variability of ecological communities may depend on species richness and composition due to a variety of statistical and ecological mechanisms. However, ecologists currently lack a general, unified theoretical framework within which to compare the effects of these mechanisms. Developing such a framework is difficult because community variability depends not just on how species vary, but also how they covary, making it unclear how to isolate the contributions of individual species to community variability. Here I develop such a theoretical framework using the multi‐level Price equation, originally developed in evolutionary biology to partition the effects of group selection and individual selection. I show how the variability of a community can be related to the properties of the individual species comprising it, just as the properties of an evolving group can be related to the properties of the individual organisms comprising it. I show that effects of species loss on community variability can be partitioned into effects of species richness (random loss of species), effects of species composition (non‐random loss of species with respect to their variances and covariances), and effects of context dependence (post‐loss changes in species’ variances and covariances). I illustrate the application of this framework using data from the Biodiversity II experiment, and show that it leads to new conceptual and empirical insights. For instance, effects of species richness on community variability necessarily occur, but often are swamped by other effects, particularly context dependence.     

Convergence of community composition during secondary succession on Zokor rodent mounds on the Tibetan Plateau

Aims The community succession theory is much debated in ecology. We studied succession on Zokor rodent mounds on the Tibetan Plateau to address several fundamental questions, among them: (i) During secondary succession, does the community composition converge towards one community state or multiple states depending on the initial colonization? (ii) Do mound communities located in different background communities exhibit different assembly trajectories?Methods In a sub-alpine meadow, we investigated a total of 80 mound communities at several successional stages in three different background communities resulting from different management histories and compared their changes in species composition. The distribution of plant communities over time was analyzed with quantitative classification and ordination methods. The co-occurrence patterns of species were evaluated at each successional stage, and the degree of convergence/divergence among communities was obtained by calculating two beta-diversity indices.Important findings During secondary succession, species richness of mound communities changed over time, and this change was dependent on the background community. Five life-form groups exhibited different dynamic patterns in species richness and plant cover. Community composition and the degree of species co-occurrence between communities increased over time since disturbance. There was much variation in species composition at earlier stages of succession, but communities on older mounds became more similar to each other and to their surrounding vegetation over the course of secondary succession. Post-disturbance succession of Zokor mound communities transitioned from 'multiple alternative states' to 'background-based deterministic community assembly' over time. Tradeoffs between competition and colonization, as well as the characteristics of different life-forms and mass effects within a limited species pool are the mechanisms responsible for convergence of mound communities.     

Life within a community: benefit to yeast long-term survival

Traditionally, living organisms have often been classified into two main categories: unicellular and multicellular. In recent years, however, the boundary between these two groups has become less strict and clear than was previously presumed. Studies on the communities formed by unicellular microorganisms have revealed that various properties and processes so far mainly associated with metazoa are also important for the proper development, survival and behaviour of muticellular microbial populations. In this review, we present various examples of this, using a yeast colony as representative of a structured organized microbial community. Among other things, we will show how the differentiation of yeast cells within a colony can be important for the long-term survival of a community under conditions of nutrient shortage, how colony development and physiology can be influenced by the environment, and how a group of colonies can synchronize their developmental changes. In the last section, we introduce examples of molecular mechanisms that can participate in some aspects of the behaviour of yeast populations.     

New insights into relationships between active and dormant organisms,phylogenetic diversity and ecosystem productivity

Marine microbes make up a key part of ocean food webs and drive ocean chemistry through a range of metabolic processes. A fundamental question in ecology is whether the diversity of organisms in a community shapes the ecological functions of that community. While there is substantial evidence to support a positive link between diversity and ecological productivity for macro‐organisms in terrestrial environments, this relationship has not previously been verified for marine microbial communities. One factor complicating the understanding of this relationship is that many marine microbes are dormant and are easily dispersed by ocean currents, making it difficult to ensure that the organisms found in a given environmental sample accurately reflect processes occurring in that environment. Another complication is that, due to microbes great range of genotypic and phenotypic variability, communities with distantly related species may have greater range of metabolic functions than communities have the same richness and evenness, but in which the species present are more closely related to each other. In this issue of Molecular Ecology, Galand et al. (2015) provide compelling evidence that the most metabolically active communities are those in which the nondormant portion of the microbial community has the highest phylogenetic diversity. They also illustrate that focusing on the active portion of the community allows for detection of temporal patterns in community structure that would not be otherwise evident. The authors’ point out that the presence of many dormant organisms that do not contribute to ecosystem functioning is a feature that makes microbial ecosystems fundamentally different from macro‐ecosystems and that this difference needs to be accounted for in microbial ecology theory.     

Mature and juvenile tissue models of regeneration in small fish species

The multitude of cells constituting organisms are fragile and easily damaged day by day. Therefore, maintenance of tissue morphology and function is fundamental for multicellular organisms to attain long life. For proper maintenance of tissue integrity, organisms must have mechanisms that detect the loss of tissue mass, activate the de novo production of cells, and organize those cells into functional tissues. However, these processes are only poorly understood. Here we give an overview of adult and juvenile tissue regeneration models in small fish species, such as zebrafish and medaka, and highlight recent advances at the molecular level. From these advances, we have come to realize that the epidermal and mesenchymal parts of the regenerating fish fin-that is, the wound epidermis and blastema, respectively-comprise heterogeneous populations of cells with different molecular identities that can be termed "compartments." These compartments and their mutual interactions are thought to play important roles in promoting the proper progression of tissue regeneration. We further describe the current understanding of these compartments and discuss the possible approaches to affording a better understanding of their roles and interactions during regeneration.     

漓江河岸带植物功能性状变异与关联

研究植物功能性状随环境梯度的变异和关联格局, 对于认识不同环境梯度下群落构建和植物适应型具有重要意义。该研究以漓江河岸带不同河段植物群落为研究对象, 调查了研究区内36个样方的物种组成, 测量了样方内42种木本植物的叶面积(LA)、比叶面积(SLA)和木材密度(WD)的功能性状值, 并运用性状梯度分析法对3个功能性状进行群落内(α组分)和群落间(β组分)组分分解及相关性分析。结果表明: (1)群落平均LA表现为中游最小且和下游差异显著, 群落平均WD则表现为中上游显著高于下游, 群落平均SLA在两两河段间均差异显著。(2)不同河段的3个植物功能性状β组分差异显著且实际观测值均小于随机模拟的零模型分布, 但α组分在河岸带不同河段均差异不显著且3个功 能性状的α组分分布范围均小于β组分, 说明在河岸带不同河段的群落构建过程中环境筛选的作用要大于群落内种间的相互作用。(3)性状SLA与LA在群落间和群落内呈现出实际观测和随机模拟的相关性均较低, 暗示了LA和SLA各自代表了植物在不同生态策略上的维度; 但SLA和WD实际观测值和随机模拟值呈现出较强的负相关关系, 暗示这2个性状对于环境筛选表现出较高的整体趋同适应性, 体现了植物功能性状对群落间环境变异的依赖性大于群落内种间相互作用的依赖性。     

Allelopathy in tropical and subtropical species

The ability of certain plants to synthesize allelochemicals that disrupt the germination, development, reproduction and/or survival of organisms that compete with them for resources has been observed in a variety of environments worldwide. Tropical and subtropical regions are particularly conducive to the evolution of allelopathic survival strategies as the relatively constant temperatures and mild frost-free winters produce a hospitable year-round growing season. This allows for the proliferation of a large variety of species and leads to fierce competition for sunlight, nutrients, water and other resources. Allelopathy provides an advantage to invasive species allowing for increased competitiveness and fitness over native and agricultural species in a variety of different habitats. Herein, the diversity and known action mechanisms of allelopathic compounds with a focus on tropical and subtropical communities is reviewed. Furthermore, the current and future prospect of utilizing and developing these allelopathic chemicals as weed control options is discussed.