Phenotypic Plasticity Changes Research Articles

A Boolean model explains phenotypic plasticity changes underlying hepatic cancer stem cells emergence

In several carcinomas, including hepatocellular carcinoma, it has been demonstrated that cancer stem cells (CSCs) have enhanced invasiveness and therapy resistance compared to differentiated cancer cells. Mathematical-computational tools could be valuable for integrating experimental results and understanding the phenotypic plasticity mechanisms for CSCs emergence. Based on the literature review, we constructed a Boolean model that recovers eight stable states (attractors) corresponding to the gene expression profile of hepatocytes and mesenchymal cells in senescent, quiescent, proliferative, and stem-like states. The epigenetic landscape associated with the regulatory network was analyzed. We observed that the loss of p53, p16, RB, or the constitutive activation of β-catenin and YAP1 increases the robustness of the proliferative stem-like phenotypes. Additionally, we found that p53 inactivation facilitates the transition of proliferative hepatocytes into stem-like mesenchymal phenotype. Thus, phenotypic plasticity may be altered, and stem-like phenotypes related to CSCs may be easier to attain following the mutation acquisition.

Early impact assessment of the paninvasive polyphagous shot hole borer beetle on commercial pear production

AbstractThe polyphagous shot hole borer (PSHB) beetle, Euwallacea fornicatus (Eichhoff) (Coleoptera: Curculionidae, Scolytinae), and its phytopathogenic fungal symbiont (Fusarium euwallaceae Freeman et al.) threaten commercial and urban tree species worldwide. This pest–fungus complex has been newly discovered in the commercial deciduous fruit industry (Western Cape, South Africa), where its effect is still unknown. This study explored the impact of PSHB infestation on fruit quality and plant water‐use efficiency (WUE) – as indicated by carbon and nitrogen stable isotope ratios – of commercially cultivated Packham's Triumph pear trees within the first year of invasion, as well as changes in phenotypic plasticity (trait expression range). The impact of PSHB infestation is currently most evident in fruit quality traits, with a clear distinction between the control and most densely attacked tree categories. Fruit and leaf traits showed high variation and a significant change in phenotypic plasticity. Increased PSHB attack density was associated with smaller, duller‐toned, sweeter fruit at the time of harvest and data tended towards reduced plant WUE. Producers can expect significant variation in fruit quality and plant WUE even in hosts without branch dieback, visible plant stress or extensive beetle breeding, especially in orchards where infestations persist beyond the first year. These findings necessitate additional research to describe the long‐term impact, examine the threat to other deciduous fruit crops and cultivars and assess the need for adapted management or harvesting methods.

Vegetative phase change causes age-dependent changes in phenotypic plasticity.

Phenotypic plasticity allows organisms to optimize traits for their environment. As organisms age, they experience diverse environments that benefit from varying degrees of phenotypic plasticity. Developmental transitions can control these age-dependent changes in plasticity, and as such, the timing of these transitions can determine when plasticity changes in an organism. Here, we investigate how the transition from juvenile-to adult-vegetative development known as vegetative phase change (VPC) contributes to age-dependent changes in phenotypic plasticity and how the timing of this transition responds to environment using both natural accessions and mutant lines in the model plant Arabidopsis thaliana. We found that the adult phase of vegetative development has greater plasticity in leaf morphology than the juvenile phase and confirmed that this difference in plasticity is caused by VPC using mutant lines. Furthermore, we found that the timing of VPC, and therefore thetime when increased plasticity is acquired, varies significantly across genotypes and environments. The consistent age-dependent changes in plasticity caused by VPC suggest that VPC may be adaptive. This genetic and environmental variation in the timing of VPC indicates the potential for population-level adaptive evolution of VPC.

Mechanically induced alterations in chromatin architecture guide the balance between cell plasticity and mechanical memory.

Phenotypic plasticity, or adaptability, of a cell determines its ability to survive and function within changing cellular environments. Changes in the mechanical environment, ranging from stiffness of the extracellular matrix (ECM) to physical stress such as tension, compression, and shear, are critical environmental cues that influence phenotypic plasticity and stability. Furthermore, an exposure to a prior mechanical signal has been demonstrated to play a fundamental role in modulating phenotypic changes that persist even after the mechanical stimulus is removed, creating stable mechanical memories. In this mini review, our objective is to highlight how the mechanical environment alters both phenotypic plasticity and stable memories through changes in chromatin architecture, mainly focusing on examples in cardiac tissue. We first explore how cell phenotypic plasticity is modulated in response to changes in the mechanical environment, and then connect the changes in phenotypic plasticity to changes in chromatin architecture that reflect short-term and long-term memories. Finally, we discuss how elucidating the mechanisms behind mechanically induced chromatin architecture that lead to cell adaptations and retention of stable mechanical memories could uncover treatment methods to prevent mal-adaptive permanent disease states.

Autophagy Is Required to Sustain Increased Intestinal Cell Proliferation during Phenotypic Plasticity Changes in Honey Bee (Apis mellifera).

Tissue phenotypic plasticity facilitates rapid adaptation of organisms to biotic and/or abiotic pressure. The reproductive capacity of honey bee workers (Apis mellifera) is plastic and responsive to pheromones produced by broods and the queen. Egg laying workers (ELWs), which could reactivate their ovaries and lay haploid eggs upon queen lost, have been commonly discussed from many aspects. However, it remains unclear whether midgut homeostasis in ELWs is affected during plastic changes. Here, we found that the expression of nutrition- and autophagy-related genes was up-regulated in the midguts of ELWs, compared with that in nurse workers (NWs) by RNA-sequencing. Furthermore, the area and number of autophagosomes were increased, along with significantly increased cell death in the midguts of ELWs. Moreover, cell cycle progression in the midguts of ELWs was increased compared with that in NWs. Consistent with the up-regulation of nutrition-related genes, the body and midgut sizes, and the number of intestinal proliferation cells of larvae reared with royal jelly (RJ) obviously increased more than those reared without RJ in vitro. Finally, cell proliferation was dramatically suppressed in the midguts of ELWs when autophagy was inhibited. Altogether, our data suggested that autophagy was induced and required to sustain cell proliferation in ELWs' midguts, thereby revealing the critical role of autophagy played in the intestines during phenotypic plasticity changes.

Plant phenotypic plasticity changes pollinator-mediated selection.

Many organisms change their phenotype in response to the environment, a phenomenon called phenotypic plasticity. Although plasticity can dramatically change the phenotype of an organism, we hardly understand how this can affect biotic interactions and the resulting phenotypic selection. Here, we use fast cycling Brassica rapa plants in an experiment in the greenhouse to study the link between plasticity and selection. We detected strong plasticity in morphology, nectar, and floral scent in response to different soil types and aphid herbivory. We found positive selection on nectar and morphological traits in hand- and bumblebee-pollinated plants. Bumblebee-mediated selection on a principal component representing plant height, flower number, and flowering time (mPC3) differed depending on soil type and herbivory. For plants growing in richer soil, selection was stronger in the absence of herbivores, whereas for plants growing in poorer soil selection was stronger with herbivory. We showed that bumblebees visited tall plants with many flowers overproportionally in plants in poor soil with herbivory (i.e., when tall plants were rare), thus causing stronger positive selection on this trait combination. We suggest that with strong plasticity under most stressful conditions, pollinator-mediated selection may promote adaptation to local environmental factors given sufficient heritability of the traits under selection.

Higher, Faster, Better: Maternal Effects Shorten Time Lags and Increase Morphological Defenses in Daphnia lumholtzi Offspring Generations

Prey species can respond to the presence of predators by inducing phenotypic plastic traits which form morphological, life history or behavioral defenses. These so-called inducible defenses have evolved within a cost-benefit framework. They are only formed when they are needed, and costs associated with defenses are saved when predators are not present. However, a disadvantage compared to permanent defenses are lag phases between predator perception and the full formation of defenses. This may be especially important when the predation risk persists for longer periods, e.g., outlasts one generation and challenges prey offspring. We hypothesized that transgenerational induced phenotypic plasticity reduces lag phases in situations where hazards threaten specimens over several generations. We tested this in three generations of the freshwater crustaceanDaphnia lumholtziusing the three-spined sticklebackGasterosteus aculeatusas predator. In the presence of chemical cues from fishD. lumholtziexpresses elongated head and tail spines. In the F0 generation defenses are constraint by a comparatively long lag phase and are not developed prior to the 3rd instar. In the F1, and F2 of induced animals this lag phase is shortened and defenses are developed upon birth. We show that induction of TGP in the mothers takes place already during the juvenile stages and transfers to the offspring generation in forms of shortened time lags and enhanced trait expression. When progeny is additionally exposed to fish cues as embryos, the addition of maternal and embryonic effects further enhances the magnitude of defense expression. Our findings detail a distinguished strategy of transgenerational phenotypic plasticity which allows to shorten lag phases of trait changes in phenotypic plasticity.

Rapid and positive responses of plants to lower precipitation predictability.

Current climate change is characterized by an increase in weather variability, which includes altered means, variance and predictability of weather parameters, and which may affect an organism's ecology and evolution. Few studies have experimentally manipulated the variability of weather parameters, and very little is known about the effects of changes in the intrinsic predictability of weather parameters on living organisms. Here, we experimentally tested the effects of differences in intrinsic precipitation-predictability on two herbaceous plants (Onobrychis viciifolia and Papaver rhoeas). Lower precipitation-predictability led to phenological advance and to an increase in reproductive success, and population growth. Both species exhibited rapid transgenerational responses in phenology and fitness-related traits across four generations that mitigated most effects of precipitation-predictability on fitness proxies of ancestors. Transgenerational responses appeared to be the result of changes in phenotypic plasticity rather than local adaptation. They mainly existed with respect to conditions prevailing during early, but not during late growth, suggesting that responses to differences in predictability during late growth might be more difficult. The results show that lower short-term predictability of precipitation positively affected fitness, rapid transgenerational responses existed and different time scales of predictability (short-term, seasonal and transgenerational predictability) may affect organisms differently. This shows that the time scale of predictability should be considered in evolutionary and ecological theories, and in assessments of the consequences of climate change.

Adaptation to climate change through genetic accommodation and assimilation of plastic phenotypes.

Theory suggests that evolutionary changes in phenotypic plasticity could either hinder or facilitate evolutionary rescue in a changing climate. Nevertheless, the actual role of evolving plasticity in the responses of natural populations to climate change remains unresolved. Direct observations of evolutionary change in nature are rare, making it difficult to assess the relative contributions of changes in trait means versus changes in plasticity to climate change responses. To address this gap, this review explores several proxies that can be used to understand evolving plasticity in the context of climate change, including space for time substitutions, experimental evolution and tests for genomic divergence at environmentally responsive loci. Comparisons among populations indicate a prominent role for divergence in environmentally responsive traits in local adaptation to climatic gradients. Moreover, genomic comparisons among such populations have identified pervasive divergence in the regulatory regions of environmentally responsive loci. Taken together, these lines of evidence suggest that divergence in plasticity plays a prominent role in adaptation to climatic gradients over space, indicating that evolving plasticity is also likely to play a key role in adaptive responses to climate change through time. This suggests that genetic variation in plastic responses to the environment (G × E) might be an important predictor of species' vulnerabilities to climate-driven decline or extinction. This article is part of the theme issue 'The role of plasticity in phenotypic adaptation to rapid environmental change'.

Characterization of Carotid Smooth Muscle Cells during Phenotypic Transition.

Vascular smooth muscle cells (VSMCs) are central players in carotid atherosclerosis plaque development. Although the precise mechanisms involved in plaque destabilization are not completely understood, it is known that VSMC proliferation and migration participate in plaque stabilization. In this study, we analyzed expression patterns of genes involved in carotid atherosclerosis development (e.g., transcription factors of regulation of SMC genes) of VSMCs located inside or outside the plaque lesion that may give clues about changes in phenotypic plasticity during atherosclerosis. VSMCs were isolated from 39 carotid plaques extracted from symptomatic and asymptomatic patients by endarterectomy. Specific biomarker expression, related with VSMC phenotype, was analyzed by qPCR, western immunoblot, and confocal microscopy. MYH11, CNN1, SRF, MKL2, and CALD1 were significantly underexpressed in VSMCs from plaques compared with VSMCs from a macroscopically intact (MIT) region, while SPP1, KLF4, MAPLC3B, CD68, and LGALS3 were found significantly upregulated in plaque VSMCs versus MIT VSMCs. The gene expression pattern of arterial VSMCs from a healthy donor treated with 7-ketocholesterol showed high similarity with the expression pattern of carotid plaque VSMCs. Our results indicate that VSMCs isolated from plaque show a typical SMC dedifferentiated phenotype with macrophage-like features compared with VSMCs isolated from a MIT region of the carotid artery. Additionally, MYH11, KLF5, and SPP1 expression patterns were found to be associated with symptomatology of human carotid atherosclerosis.

Gene expression plasticity in response to salinity acclimation in threespine stickleback ecotypes from different salinity habitats.

Phenotypic plasticity is thought to facilitate the colonization of novel environments and shape the direction of evolution in colonizing populations. However, the relative prevalence of various predicted patterns of changes in phenotypic plasticity following colonization remains unclear. Here, we use a whole-transcriptome approach to characterize patterns of gene expression plasticity in the gills of a freshwater-adapted and a saltwater-adapted ecotype of threespine stickleback (Gasterosteus aculeatus) exposed to a range of salinities. The response of the gill transcriptome to environmental salinity had a large shared component common to both ecotypes (2159 genes) with significant enrichment of genes involved in transmembrane ion transport and the restructuring of the gill epithelium. This transcriptional response to freshwater acclimation is induced at salinities below two parts per thousand. There was also differentiation in gene expression patterns between ecotypes (2515 genes), particularly in processes important for changes in the gill structure and permeability. Only 508 genes that differed between ecotypes also responded to salinity and no specific processes were enriched among this gene set, and an even smaller number (87 genes) showed evidence of changes in the extent of the response to salinity acclimation between ecotypes. No pattern of relative expression dominated among these genes, suggesting that neither gains nor losses of plasticity dominated the changes in expression patterns between the ecotypes. These data demonstrate that multiple patterns of changes in gene expression plasticity can occur following colonization of novel habitats.

Ecological Epigenetics in Marine Metazoans

In this horizon scan article, I review the emerging area of ecological epigenetics in marine animals with studies of DNA methylation as the primary focus. Epigenetic mechanisms such as DNA methylation have the capacity to create rapid changes in phenotypic plasticity. Epigenetic modifications of DNA are mechanisms that modify gene expression, and may do so in marine animals in an environmentally-induced manner. Thus, changes in the transcriptome that are driven by DNA methylation in response to environmental change may be one process by which marine animals can respond to anthropogenic, environmental change. From a technical standpoint, assays to quantify levels of DNA methylation, and next-generation sequencing approaches are opening up new avenues of exploration, such as simultaneously profiling the transcriptome and the methylome. A horizon scan for this topic suggests that the use of epigenomics and other methods to quantify DNA methylation will likely reveal important mechanisms of response to rapid environmental change in marine metazoans.

Adaptation to heat stress reduces phenotypic and transcriptional plasticity in a marine copepod

Summary Organisms may respond to changing environments through phenotypic plasticity or adaptive evolution. These two processes are not mutually exclusive and may either dampen or strengthen each other's effects, depending on the genetic correlation between trait values and the slopes of their norms of reaction. To examine the effect of adaptation to heat stress on the plasticity of heat tolerance, we hybridized populations of the crustacean Tigriopus californicus that show divergent phenotypes for heat tolerance. We then selected for increased heat tolerance in hybrids and measured heat tolerance and the phenotypic plasticity of heat tolerance in both selected lines and unselected controls. To test whether the changes in phenotypic plasticity were associated with changes in the plasticity of gene expression, we also sequenced transcriptomes of selected and unselected lines, both under heat shock and at ambient temperatures. We observed increased heat tolerance in selected lines, but also lower phenotypic and transcriptional plasticity in response to heat stress. The plastic response to heat stress was highly enriched for hydrolytic and catalytic activities, suggesting a prominent role for degradation of misfolded proteins. Our findings have important implications for biological responses to climate change: if adaptation to environmental stress reduces plasticity, then plasticity and adaptive evolution will make overlapping, rather than additive contributions to buffering populations from environmental change.

Changes in resource-use strategy and phenotypic plasticity associated with selection for yield in wild species native to arid environments

Along history, wild plants have been introduced into cultivation and domestic derivatives radically altered by this move due to changes in selection pressure: wild species are exposed to natural selection that operates to continue survival and domesticated species to artificial selection that emphasized yield. Here we assess whether selection for yield triggered a shift in resource-use strategy and changes in phenotypic plasticity. We compared co-generic wild and domesticated species grown in a common garden under two levels of water availabilities. Our results indicate that resource-use strategy shifted from conservative to acquisitive. The change in selection force from survival to reproduction provoked an increase in mean values of reproduction-related traits and a decrease in survival-related traits. Trade-offs between reproduction and storage were found in both groups. This occurred concurrently with an increase in phenotypic plasticity of most traits. Wild species showed higher homeostasis than domesticated species. Despite the lesser homeostasis of the latter, improvements in reproductive traits were not completely reversible under low resource availability: across environments domesticated species always showed higher reproductive biomass and reproductive effort than their wild relatives. The combination of higher mean values of advantageous traits and greater plasticity might contribute to the success of domesticated species in plentiful environments.

Genetic accommodation and behavioural evolution: insights from genomic studies

Many behaviours vary in response to the environment (biotic or abiotic) and therefore represent an interesting form of phenotypic plasticity. Behavioural plasticity, like other plastic traits, can evolve through genetic assimilation or accommodation. However, little is known about the nature of changes in gene expression plasticity that accompanies these evolutionary changes in phenotypic plasticity. We know that variation in gene expression level, a first-order phenotype, underlies much behavioural variation. Several studies have begun to document which genes show expression-level variation related to plastic changes in behaviour as well as evolved changes in behaviour. Advances in sequencing technology allow us to address these questions on a genomic scale. By characterizing changes in gene expression according to the concept of a norm of reaction one can describe the evolved patterns of gene expression that accompany the evolution of behavioural plasticity. Here, we describe how genomic approaches can help us understand changes in gene expression that accompany or underlie the evolution of behavioural plasticity. To do this, we provide a framework of classification for the evolved patterns of gene expression plasticity that could underlie genetic assimilation or accommodation of behaviour. We provide examples of genetic assimilation from the animal behaviour and animal physiology literature that have been, or can be, studied at a genomic level. We then describe the characteristics of an appropriate study system and briefly address experimental design using the available genomic tools in a comparative context. Studying the patterns of gene expression associated with genetic assimilation will elucidate processes by which behavioural plasticity has evolved.

Daphnia Paleogenetics and Environmental Change: Deconstructing the Evolution of Plasticity

AbstractIt is only recently that ecologists, including limnologists, have begun to appreciate the potential for organisms to evolve rapidly in response to environmental change. The resulting changes in the mean characteristics of the evolving populations have the potential to alter population, community and ecosystem responses to environmental changes – while those changes are still taking place. Viable diapausing eggs of zooplankton buried annually in lake sediments represent an historical record of the genotypes present at a series of time points in the past, typically dating back several decades. Because these eggs can be extracted from sediment layers of known age and hatched, the phenotypes of past populations can be reconstructed and evolutionary responses to recent environmental change revealed. This is especially valuable for investigating the nature of evolution of phenotypically plastic traits for which trait expression in different environmental conditions must be measured using living animals. When animals, hatched from sediments deposited at different times during a period of rapid change in the lake environment, are reared under a range of laboratory conditions, the nature of plasticity evolution can be discovered. Here, we use the results of two previously published studies of Daphnia evolutionary response to anthropogenic environmental change to deconstruct the patterns and rates of genetic changes in phenotypic plasticity. We find for the populations studied that (1) in three of four instances, plasticity evolved primarily by changes in the trait expressed in the environmental condition for which selection acted most strongly, rather than purely as a change in slope, and (2) the rates of evolution of plasticity were comparable to those for constitutive traits reported in the literature suggesting that plasticity does not necessarily retard the rate of evolution. Because Daphnia is a critical species in many limnetic ecosystems, and because in both of our study systems the characteristics of the Daphnia populations that evolved are known to influence community and ecosystem processes, this rapid adaptive evolution may be a critical component of population, community and ecosystem response to the accelerating pace of environmental change.Plus ça change, plus c'est la même chose Jean‐Baptists Alphonse Karr, Les Guêpes, January 1849 (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)

EVOLUTIONARY RESPONSES TO ENVIRONMENTAL HETEROGENEITY IN CENTRAL AMERICAN ECHINOID LARVAE: PLASTIC VERSUS CONSTANT PHENOTYPES

Do changes in food resources lead to evolutionary changes in phenotypic plasticity or in different constant phenotypes? I addressed this question by studying plasticity of larval feeding arms for "geminate species pairs" in three echinoid genera. These closely related species were geographically isolated when the Panamanian Isthmus raised 2.8-3.1 million years ago, creating two different food level environments: high but variable food levels in the eastern Pacific versus chronically low food levels in the western Caribbean. I reared larvae of geminate species in different replicated food environments for 10 days postfertilization, collected morphological measurements of individual arm and body lengths, and calculated degrees of plasticity of relative arm length for each species. In contrast to previous studies with temperate echinoids, there was no significant plasticity of arm length in either the Pacific or Caribbean species considered here. Caribbean species, however, had significantly longer relative arm lengths than Pacific species, regardless of food levels. These results suggest that historical changes in food levels have led to the evolution of constant rather than plastic differences between Pacific and Caribbean echinoids. The evolution of plasticity may be limited by the timing of reproduction or by egg size in this system.

Extensive phenotypic variation in early flowering mutants of Arabidopsis.

Flowering time, the major regulatory transition of plant sequential development, is modulated by multiple endogenous and environmental factors. By phenotypic profiling of 80 early flowering mutants of Arabidopsis, we examine how mutational reduction of floral repression is associated with changes in phenotypic plasticity and stability. Flowering time measurements in mutants reveal deviations from the linear relationship between the number of leaves and number of days to bolting described for natural accessions and late flowering mutants. The deviations correspond to relative early bolting and relative late bolting phenotypes. Only a minority of mutants presents no detectable phenotypic variation. Mutants are characterized by a broad release of morphological pleiotropy under short days, with leaf characters being most variable. They also exhibit changes in phenotypic plasticity across environments for florigenic-related responses, including the reaction to light and dark, photoperiodic behavior, and Suc sensitivity. Morphological pleiotropy and plasticity modifications are differentially distributed among mutants, resulting in a large diversity of multiple phenotypic changes. The pleiotropic effects observed may indicate that floral repression defects are linked to global developmental perturbations. This first, to our knowledge, extensive characterization of phenotypic variation in early flowering mutants correlates with the reports that most factors recruited in floral repression at the molecular genetic level correspond to ubiquitous regulators. We discuss the importance of functional ubiquity for floral repression with respect to robustness and flexibility of network biological systems.

Evolutionary responses of Drosophila melanogaster to selection at different larval densities: changes in genetic variation, specialization and phenotypic plasticity

Abstract We studied the evolutionary response to novel environments by applying artificial selection for total progeny biomass in populations of Drosophila melanogaster maintained at three different larval population densities. We found the relative amount of genetic variability for characters related with biomass to be lower and the correlation between them more negative at the intermediate density, and that selection resulted in changes in phenotypic plasticity and in patterns of resource allocation between traits. We found some evidence for tradeoffs between densities, which suggests that populations living at heterogeneous densities might be subject to disruptive selection. Our results show that adaptation to new environments may be a complex process, involving not only changes in trait means, but also in correlations between traits and between environments.