The role of plasticity and stochasticity in coexistence.

Species coexistence in ecological communities is a central feature of biodiversity. Different concepts, i.e., contemporary niche theory, modern coexistence theory, and the unified neutral theory, have identified many building blocks of such ecological assemblies. However, other factors, such as phenotypic plasticity and stochastic inter-individual variation, have received little attention, in particular in animals. For example, how resource polyphenisms resulting in predator-prey interactions affect coexistence is currently unknown. Here, we present an integrative theoretical-experimental framework using the nematode plasticity model Pristionchus pacificus with its well-studied mouth-form dimorphism resulting in cannibalism. We develop an individual-based model that relies upon synthetic data based on our empirical measurements of fecundity and polyphenism to preserve demographic heterogeneity. We demonstrate how the interplay between plasticity and individual stochasticity result in all-or-nothing outcomes at the local level. Coexistence is made possible when spatial structure is introduced.

Spatial and temporal heterogeneity alter the cost of plasticity in Pristionchus pacificus.

Phenotypic plasticity, the ability of a single genotype to produce distinct phenotypes under different environmental conditions, has become a leading concept in ecology and evolutionary biology, with the most extreme examples being the formation of alternative phenotypes (polyphenisms). However, several aspects associated with phenotypic plasticity remain controversial, such as the existence of associated costs. While already predicted by some of the pioneers of plasticity research, i.e. Schmalhausen and Bradshaw, experimental and theoretical approaches have provided limited support for the costs of plasticity. In experimental studies, one common restriction is the measurement of all relevant parameters over long time periods. Similarly, theoretical studies rarely use modelling approaches that incorporate specific experimentally-derived fitness parameters. Therefore, the existence of the costs of plasticity remains disputed. Here, we provide an integrative approach to understand the cost of adaptive plasticity and its ecological ramifications, by combining laboratory data from the nematode plasticity model system Pristionchus pacificus with a stage-structured population model. Taking advantage of measurements of two isogenic strains grown on two distinct diets, we illustrate how spatial and temporal heterogeneity with regard to the distribution of resources on a metapopulation can alter the outcome of the competition and alleviate the realized cost of plasticity.

Genetic drift promotes and recombination hinders speciation on holey fitness landscapes.

Dobzhansky and Muller proposed a general mechanism through which microevolution, the substitution of alleles within populations, can cause the evolution of reproductive isolation between populations and, therefore, macroevolution. As allopatric populations diverge, many combinations of alleles differing between them have not been tested by natural selection and may thus be incompatible. Such genetic incompatibilities often cause low fitness in hybrids between species. Furthermore, the number of incompatibilities grows with the genetic distance between diverging populations. However, what determines the rate and pattern of accumulation of incompatibilities remains unclear. We investigate this question by simulating evolution on holey fitness landscapes on which genetic incompatibilities can be identified unambiguously. We find that genetic incompatibilities accumulate more slowly among genetically robust populations and identify two determinants of the accumulation rate: recombination rate and population size. In large populations with abundant genetic variation, recombination selects for increased genetic robustness and, consequently, incompatibilities accumulate more slowly. In small populations, genetic drift interferes with this process and promotes the accumulation of genetic incompatibilities. Our results suggest a novel mechanism by which genetic drift promotes and recombination hinders speciation.

The role of microRNAs in neurobiology and pathophysiology of the hippocampus.

MicroRNAs (miRNAs) are short non-coding and well-conserved RNAs that are linked to many aspects of development and disorders. MicroRNAs control the expression of genes related to different biological processes and play a prominent role in the harmonious expression of many genes. During neural development of the central nervous system, miRNAs are regulated in time and space. In the mature brain, the dynamic expression of miRNAs continues, highlighting their functional importance in neurons. The hippocampus, as one of the crucial brain structures, is a key component of major functional connections in brain. Gene expression abnormalities in the hippocampus lead to disturbance in neurogenesis, neural maturation and synaptic formation. These disturbances are at the root of several neurological disorders and behavioral deficits, including Alzheimer's disease, epilepsy and schizophrenia. There is strong evidence that abnormalities in miRNAs are contributed in neurodegenerative mechanisms in the hippocampus through imbalanced activity of ion channels, neuronal excitability, synaptic plasticity and neuronal apoptosis. Some miRNAs affect oxidative stress, inflammation, neural differentiation, migration and neurogenesis in the hippocampus. Furthermore, major signaling cascades in neurodegeneration, such as NF-Kß signaling, PI3/Akt signaling and Notch pathway, are closely modulated by miRNAs. These observations, suggest that microRNAs are significant regulators in the complicated network of gene regulation in the hippocampus. In the current review, we focus on the miRNA functional role in the progression of normal development and neurogenesis of the hippocampus. We also consider how miRNAs in the hippocampus are crucial for gene expression mechanisms in pathophysiological pathways.

Experimental and theoretical support for costs of plasticity and phenotype in a nematode cannibalistic trait.

Developmental plasticity is the ability of a genotype to express multiple phenotypes under different environmental conditions and has been shown to facilitate the evolution of novel traits. However, while the associated cost of plasticity, i.e., the loss in fitness due to the ability to express plasticity in response to environmental change, and the cost of phenotype, i.e., the loss of fitness due to expressing a fixed phenotype across environments, have been theoretically predicted, empirically such costs remain poorly documented and little understood. Here, we use a plasticity model system, hermaphroditic nematode Pristionchus pacificus, to experimentally measure these costs in wild isolates under controlled laboratory conditions. P. pacificus can develop either a bacterial feeding or predatory mouth morph in response to different external stimuli, with natural variation of mouth-morph ratios between strains. We first demonstrated the cost of phenotype by analyzing fecundity and developmental speed in relation to mouth morphs across the P. pacificus phylogenetic tree. Then, we exposed P. pacificus strains to two distinct microbial diets that induce strain-specific mouth-form ratios. Our results indicate that the plastic strain does shoulder a cost of plasticity, i.e., the diet-induced predatory mouth morph is associated with reduced fecundity and slower developmental speed. In contrast, the non-plastic strain suffers from the cost of phenotype since its phenotype does not change to match the unfavorable bacterial diet but shows increased fitness and higher developmental speed on the favorable diet. Furthermore, using a stage-structured population model based on empirically derived life history parameters, we show how population structure can alleviate the cost of plasticity in P. pacificus. The results of the model illustrate the extent to which the costs associated with plasticity and its effect on competition depend on ecological factors. This study provides support for costs of plasticity and phenotype based on empirical and modeling approaches.

Population-level heterogeneity as a reflection of mixed strategy: A computational perspective on the Crabtree effect.

Is population-level heterogeneity a reflection of distinct subpopulations, exhibiting different metabolic functions, or dynamic metabolism of individuals within the population? This fascinating question has remained a subject of great interest in studying metabolic specialization in microorganisms. The Crabtree effect - i.e., the ability of some microorganisms to switch from respiration to fermentation in the presence of oxygen - is an appropriate case study to address the aforementioned question. Game-theoretical approaches have been routinely used to examine and explain the way a microorganism, such as yeast, would switch between the two ATP-producing pathways, i.e., respiration and fermentation. Here we attempt to explain the switch between respiration and fermentation in yeast by constructing a simple metabolic switch. We then utilize an individual-based model, in which each individual is equipped with all the relevant chemical reactions, to see how cells equipped with such metabolic switch would behave in different conditions. We further investigate our proposed metabolic switch using the game-theoretical approach. Based on this model, we postulate that the population-level metabolic heterogeneity in microorganisms can simply arise from individuals utilizing a mixed strategy.

Sex or cannibalism: Polyphenism and kin recognition control social action strategies in nematodes.

Resource polyphenisms, where single genotypes produce alternative feeding strategies in response to changing environments, are thought to be facilitators of evolutionary novelty. However, understanding the interplay between environment, morphology, and behavior and its significance is complex. We explore a radiation of Pristionchus nematodes with discrete polyphenic mouth forms and associated microbivorous versus cannibalistic traits. Notably, comparing 29 Pristionchus species reveals that reproductive mode strongly correlates with mouth-form plasticity. Male-female species exhibit the microbivorous morph and avoid parent-offspring conflict as indicated by genetic hybrids. In contrast, hermaphroditic species display cannibalistic morphs encouraging competition. Testing predation between 36 co-occurring strains of the hermaphrodite P. pacificus showed that killing inversely correlates with genomic relatedness. These empirical data together with theory reveal that polyphenism (plasticity), kin recognition, and relatedness are three major factors that shape cannibalistic behaviors. Thus, developmental plasticity influences cooperative versus competitive social action strategies in diverse animals.

Competitive exclusion during co-infection as a strategy to prevent the spread of a virus: A computational perspective.

Inspired by the competition exclusion principle, this work aims at providing a computational framework to explore the theoretical feasibility of viral co-infection as a possible strategy to reduce the spread of a fatal strain in a population. We propose a stochastic-based model-called Co-Wish-to understand how competition between two viruses over a shared niche can affect the spread of each virus in infected tissue. To demonstrate the co-infection of two viruses, we first simulate the characteristics of two virus growth processes separately. Then, we examine their interactions until one can dominate the other. We use Co-Wish to explore how the model varies as the parameters of each virus growth process change when two viruses infect the host simultaneously. We will also investigate the effect of the delayed initiation of each infection. Moreover, Co-Wish not only examines the co-infection at the cell level but also includes the innate immune response during viral infection. The results highlight that the waiting times in the five stages of the viral infection of a cell in the model-namely attachment, penetration, eclipse, replication, and release-play an essential role in the competition between the two viruses. While it could prove challenging to fully understand the therapeutic potentials of viral co-infection, we discuss that our theoretical framework hints at an intriguing research direction in applying co-infection dynamics in controlling any viral outbreak's speed.

Noise-driven cell differentiation and the emergence of spatiotemporal patterns.

The emergence of phenotypic diversity in a population of cells and their arrangement in space and time is one of the most fascinating features of living systems. In fact, understanding multicellularity is unthinkable without explaining the proximate and the ultimate causes of cell differentiation in time and space. Simpler forms of cell differentiation can be found in unicellular organisms, such as bacterial biofilm, where reversible cell differentiation results in phenotypically diverse populations. In this manuscript, we attempt to start with the simple case of reversible nongenetic phenotypic to construct a model of differentiation and pattern formation. Our model, which we refer to as noise-driven differentiation (NDD) model, is an attempt to consider the prevalence of noise in biological systems, alongside what is known about genetic switches and signaling, to create a simple model which generates spatiotemporal patterns from bottom-up. Our simulations indicate that the presence of noise in cells can lead to reversible differentiation and the addition of signaling can create spatiotemporal pattern.

From indication to decision: A hierarchical approach to model the chemotactic behavior of Escherichia coli.

Reducing the complex behavior of living entities to its underlying physical and chemical processes is a formidable task in biology. Complex behaviors can be characterized as decision making: the ability to process the incoming information via an intracellular network and act upon this information to choose appropriate strategies. Motility is one such behavior that has been the focus many modeling efforts in the past. Our aim is to reduce the chemotactic behavior in Escherichia coli to its molecular constituents in order to paint a comprehensive and end-to-end picture of this intricate behavior. We utilize a hierarchical approach, consisting of three layers, to achieve this goal: at the first level, chemical reactions involved in chemotaxis are simulated. In the second level, the chemical reactions give rise to the mechanical movement of six independent flagella. At the last layer, the two lower layers are combined to allow a digital bacterium to receive information from its environment and swim through it with verve. Our results are in concert with the experimental studies concerning the motility of E.coli cells. In addition, we show that our detailed model of chemotaxis is reducible to a non-homogeneous Markov process.

Spiraling Complexity: A Test of the Snowball Effect in a Computational Model of RNA Folding.

Genetic incompatibilities can emerge as a byproduct of genetic divergence. According to Dobzhansky and Muller, an allele that fixes in one population may be incompatible with an allele at a different locus in another population when the two alleles are brought together in hybrids. Orr showed that the number of Dobzhansky-Muller incompatibilities (DMIs) should accumulate faster than linearly-i.e., snowball-as two lineages diverge. Several studies have attempted to test the snowball effect using data from natural populations. One limitation of these studies is that they have focused on predictions of the Orr model, but not on its underlying assumptions. Here, we use a computational model of RNA folding to test both predictions and assumptions of the Orr model. Two populations are allowed to evolve in allopatry on a holey fitness landscape. We find that the number of inviable introgressions (an indicator for the number of DMIs) snowballs, but does so more slowly than expected. We show that this pattern is explained, in part, by the fact that DMIs can disappear after they have arisen, contrary to the assumptions of the Orr model. This occurs because DMIs become progressively more complex (i.e., involve alleles at more loci) as a result of later substitutions. We also find that most DMIs involve >2 loci, i.e., they are complex. Reproductive isolation does not snowball because DMIs do not act independently of each other. We conclude that the RNA model supports the central prediction of the Orr model that the number of DMIs snowballs, but challenges other predictions, as well as some of its underlying assumptions.