Does phenotypic plasticity initiate developmental bias?

The generation of variation is paramount for the action of natural selection. Although biologists are now moving beyond the idea that random mutation provides the sole source of variation for adaptive evolution, we still assume that variation occurs randomly. In this review, we discuss an alternative view for how phenotypic plasticity, which has become well accepted as a source of phenotypic variation within evolutionary biology, can generate nonrandom variation. Although phenotypic plasticity is often defined as a property of a genotype, we argue that it needs to be considered more explicitly as a property of developmental systems involving more than the genotype. We provide examples of where plasticity could be initiating developmental bias, either through direct active responses to similar stimuli across populations or as the result of programmed variation within developmental systems. Such biased variation can echo past adaptations that reflect the evolutionary history of a lineage but can also serve to initiate evolution when environments change. Such adaptive programs can remain latent for millions of years and allow development to harbor an array of complex adaptations that can initiate new bouts of evolution. Specifically, we address how ideas such as the flexible stem hypothesis and cryptic genetic variation overlap, how modularity among traits can direct the outcomes of plasticity, and how the structure of developmental signaling pathways is limited to a few outcomes. We highlight key questions throughout and conclude by providing suggestions for future research that can address how plasticity initiates and harbors developmental bias.     

Unravelling phenotypic plasticity -- why should we bother?

The ability of a genotype to change its phenotype was once considered rather a nuisance -- making it difficult to define a genotype. This led to the idea that there was a problem called 'instability'. But quite early it was recognized that stability was under genetic control, and was a character like other attributes of an individual. From this realization came the idea that there were two sides to the character of 'instability', and that the ability to change could be important. This ability was thus given the title of 'plasticity'. Once recognized, it became clear from surveys of different species and populations that plasticity can (i) be a complex character, and (ii) be selected to fit species to the particular demands of different environments. For plants, which cannot meet variations in environment like animals by behavioural responses, phenotypic plasticity can be very important. Plants should therefore be valuable tools for unravelling the mechanisms of plasticity whilst also demonstrating its contribution to fitness experimentally. We ought also to be able to demonstrate that appropriate genetic variability is available through which complex responses can be built up by selection. Genes must exist not only to determine character means, but also to determine character response, which adds interesting complexity to our ideas about evolution.     

How many processes are responsible for phenotypic evolution?

SUMMARY In addressing phenotypic evolution, this article reconsiders natural selection, random drift, developmental constraints, and internal selection in the new extended context of evolutionary developmental biology. The change of perspective from the "evolution of phenotypes" toward an "evolution of ontogenies" (evo-devo perspective) affects the reciprocal relationships among these different processes. Random drift and natural selection are sibling processes: two forms of post-productional sorting among alternative developmental trajectories, the former random, the latter nonrandom. Developmental constraint is a compound concept; it contains even some forms of natural ("external" and "internal") selection. A narrower definition ("reproductive constraints") is proposed. Internal selection is not a selection caused by an internal agent. It is a form of environment-independent selection depending on the level of the organism's internal developmental or functional coordination. Selection and constraints are the main deterministic processes in phenotypic evolution but they are not opposing forces. Indeed, they are continuously interacting processes of evolutionary change, but with different roles that should not be confused.     

Do plants and animals differ in phenotypic plasticity?

This paper compares the flexibility in the nexus between phenotype and genotype in plants and animals. These taxa although considered to be fundamentally different are found to be surprisingly similar in the mechanisms used to achieve plasticity. Although non-cognitive behaviour occurs in plants, its range is limited, while morphological and developmental plasticity also occur to a considerable extent in animals. Yet both plants and animals are subject to unique constraints and thus need to find unique solutions to functional problems. A true comparison between the plant and animal phenotype would be a comparison between plants and sessile photosynthesizing colonial invertebrates. Such comparisons are lacking. However, they would provide important insights into the adaptive significance of plasticity in these groups. It is also suggested that a comparison of inflexible traits in these groups would provide an understanding of the constraints, as well as the costs and benefits, of a plastic versus non-plastic phenotype in plants and animals.     

An extensive phenotypic characterization of the hTNFα transgenic mice

Background

Tumor necrosis factor alpha (TNFα) is implicated in a wide variety of pathological and physiological processes, including chronic inflammatory conditions, coronary artery disease, diabetes, obesity, and cachexia. Transgenic mice expressing human TNFα (hTNFα) have previously been described as a model for progressive rheumatoid arthritis. In this report, we describe extensive characterization of an hTNFα transgenic mouse line.

Results

In addition to arthritis, these hTNFα transgenic mice demonstrated major alterations in body composition, metabolic rate, leptin levels, response to a high-fat diet, bone mineral density and content, impaired fertility and male sexual function. Many phenotypes displayed an earlier onset and a higher degree of severity in males, pointing towards a significant degree of sexual dimorphism in response to deregulated expression of TNFα.

Conclusion

These results highlight the potential usefulness of this transgenic model as a resource for studying the progressive effects of constitutively expressed low levels of circulating TNFα, a condition mimicking that observed in a number of human pathological conditions.     

Empirically derived phenotypic subgroups – qualitative and quantitative trait analyses

Background

The Framingham Heart Study has contributed a great deal to advances in medicine. Most of the phenotypes investigated have been univariate traits (quantitative or qualitative). The aims of this study are to derive multivariate traits by identifying homogeneous groups of people and assigning both qualitative and quantitative trait scores; to assess the heritability of the derived traits; and to conduct both qualitative and quantitative linkage analysis on one of the heritable traits.

Methods

Multiple correspondence analysis, a nonparametric analogue of principal components analysis, was used for data reduction. Two-stage clustering, using both k-means and agglomerative hierarchical clustering, was used to cluster individuals based upon axes (factor) scores obtained from the data reduction. Probability of cluster membership was calculated using binary logistic regression. Heritability was calculated using SOLAR, which was also used for the quantitative trait analysis. GENEHUNTER-PLUS was used for the qualitative trait analysis.

Results

We found four phenotypically distinct groups. Membership in the smallest group was heritable (38%, p < 1 × 10^-6) and had characteristics consistent with atherogenic dyslipidemia. We found both qualitative and quantitative LOD scores above 3 on chromosomes 11 and 14 (11q13, 14q23, 14q31). There were two Kong &; Cox LOD scores above 1.0 on chromosome 6 (6p21) and chromosome 11 (11q23).

Conclusion

This approach may be useful for the identification of genetic heterogeneity in complex phenotypes by clarifying the phenotype definition prior to linkage analysis. Some of our findings are in regions linked to elements of atherogenic dyslipidemia and related diagnoses, some may be novel, or may be false positives.

     

Cadmium‐induced apoptosis and phenotypic changes in mouse thymocytes

At present cadmium (Cd)induced immunotoxicity and the mechanisms involved have not been fully elucidated. The main objective of the present study is to explore the apoptogenic property of Cd in primary cultured mouse thymocytes and its effect on cell surface marker expression and phenotypic changes. Cdinduced thymocyte apoptosis was determined by TdTmediated dUTP nick end labeling (TUNEL) assay, DNA content/cell cycle analysis and DNA gel electrophoresis. The results showed that Cd was able to cause apoptosis in mouse thymocytes in a time and dosedependent manner. Moreover, different subsets of thymocytes possessed different susceptibility to the apoptotic effect of Cd, in the order of CD8⁺ > CD4^–CD8^– (double negative cells, DN) > CD4⁺CD8⁺ (double positive cells, DP) > CD4⁺. Cd treatment also altered thymocyte surface marker expression, leading to evident phenotypic changes. Such changes were characterized by a decline in DP cells and a marked decrease in CD4⁺/CD8⁺ ratio, mainly due to a significant increase in CD8⁺ subsets. These observations help to obtain a better understanding of the immunotoxic and immunomodulatory effects of Cd.     

Which evolutionary processes influence natural genetic variation for phenotypic traits?

Although many studies provide examples of evolutionary processes such as adaptive evolution, balancing selection, deleterious variation and genetic drift, the relative importance of these selective and stochastic processes for phenotypic variation within and among populations is unclear. Theoretical and empirical studies from humans as well as natural animal and plant populations have made progress in examining the role of these evolutionary forces within species. Tentative generalizations about evolutionary processes across species are beginning to emerge, as well as contrasting patterns that characterize different groups of organisms. Furthermore, recent technical advances now allow the combination of ecological measurements of selection in natural environments with population genetic analysis of cloned QTLs, promising advances in identifying the evolutionary processes that influence natural genetic variation.     

Duplication 15q22»15qter and its phenotypic expression

Summary Two infants with dysmorphism and aortic stenosis were trisomic for the distal part of 15q. Similar to seven other published cases, the facial dysmorphism was characteristic: prominent nose, narrow palpebral fissures, slight anti-mongoloïd slant, low-set ears, long upper lip, and a pronounced philtrum. Laboratory studies failed to demonstrate a gene-dose effect for the enzymes coded by chromosome 15 (PK 3 and MPI) and chromosome 21 (SOD 1).     

Evolution of phenotypic plasticity: where are we going now?

The study of phenotypic plasticity has progressed significantly over the past few decades. We have moved from variation for plasticity being considered as a nuisance in evolutionary studies to it being the primary target of investigations that use an array of methods, including quantitative and molecular genetics, as well as of several approaches that model the evolution of plastic responses. Here, I consider some of the major aspects of research on phenotypic plasticity, assessing where progress has been made and where additional effort is required. I suggest that some areas of research, such the study of the quantitative genetic underpinning of plasticity, have been either settled in broad outline or superseded by new approaches and questions. Other issues, such as the costs of plasticity are currently at the forefront of research in this field, and are likely to be areas of major future development.     

Genetic and phenotypic targeting of β-adrenergic signaling in heart failure

Heart failure is a leading cause of hospitalization worldwide. No major significant improvements in prognosis have been achieved for heart failure over the last several decades despite advances in disease management. Heart failure itself represents a final common endpoint for several disease entities, including hypertension and coronary artery disease. On a molecular level, certain biochemical features remain common to failing myocardium. Among these are alterations in the -adrenergic receptor (-AR) signaling cascade. Recent advances in transgenic and gene therapy techniques have presented novel therapeutic strategies for management of heart failure via genetic manipulation of -AR signaling including the targeted inhibition of the -AR kinase (ARK1 or GRK2). In this review, we will discuss the -AR signaling changes that accompany heart failure as well as corresponding therapeutic strategies. We will then review the evidence from transgenic mouse work supporting the use of -AR manipulation in the failing heart and more recent in vivo applications of gene therapy directed at reversing or preventing heart failure. (Mol Cell Biochem 263: 5–9, 2004)     

What drives phenotypic divergence among coral clonemates of Acropora palmata?

Evolutionary rescue of populations depends on their ability to produce phenotypic variation that is heritable and adaptive. DNA mutations are the best understood mechanisms to create phenotypic variation, but other, less well‐studied mechanisms exist. Marine benthic foundation species provide opportunities to study these mechanisms because many are dominated by isogenic stands produced through asexual reproduction. For example, Caribbean acroporid corals are long lived and reproduce asexually via breakage of branches. Fragmentation is often the dominant mode of local population maintenance. Thus, large genets with many ramets (colonies) are common. Here, we observed phenotypic variation in stress responses within genets following the coral bleaching events in 2014 and 2015 caused by high water temperatures. This was not due to genetic variation in their symbiotic dinoflagellates (Symbiodinium “fitti”) because each genet of this coral species typically harbours a single strain of S. “fitti”. Characterization of the microbiome via 16S tag sequencing correlated the abundance of only two microbiome members (Tepidiphilus, Endozoicomonas) with a bleaching response. Epigenetic changes were significantly correlated with the host's genetic background, the location of the sampled polyps within the colonies (e.g., branch vs. base of colony), and differences in the colonies’ condition during the bleaching event. We conclude that long‐term microenvironmental differences led to changes in the way the ramets methylated their genomes, contributing to the differential bleaching response. However, most of the variation in differential bleaching response among clonemates of Acropora palmata remains unexplained. This research provides novel data and hypotheses to help understand intragenet variability in stress phenotypes of sessile marine species.     

How much do phenotypic plasticity and local genetic variation contribute to phenotypic divergences along environmental gradients in widespread invasive plants? A meta‐analysis

For introduced species that have spread across a wide distributional range, phenotypic plasticity (PLA) has often been proposed as an important contributor to invasion success, because it increases the survival rate during initial colonization. In contrast, local genetic variation (LOC) has also been proposed to be important, because it could allow invaders to evolve high performance in a new habitat. While evolutionary ecologists have long been interested in understanding genetic mechanisms that allow rapid colonization and spread of species, until recently experimental tests of these concepts have been limited. As a step towards generalization in our understanding of the importance of PLA and LOC, we review the current state of the literature on this topic using meta‐analysis. Here, we focused on three fundamental questions: 1) which strategy, PLA or LOC, better explains the phenotypic divergences during invader range expansion across different environmental gradients? 2) Which species characteristics correlate with the occurrence of these different phenomena? And 3) does the detection of PLA versus LOC depend on the trait studied? Using meta‐analysis we found that plasticity explained a higher proportion of phenotypic variation regardless of the environmental gradients studied or plant growth forms. PLA predominated in clonal, self‐compatible and perennial species, while LOC predominated in annual species. The patterns were trait‐dependent: LOC was significantly more important than PLA in phenology, while opposite patterns were found in fecundity and biomass allocation. The frequent simultaneous detection of PLA and genotypic variation in PLA among invasive populations suggested that PLA might benefit from LOC to some extent. Our results also indicate that the contribution of plasticity to the competitive advantages of invasive plants may be more informative than the level of plasticity itself. Synthesis For invasive plants that spread across a wide distributional range, understanding the mechanisms that allow rapid colonization and spread is crucial. Phenotypic plasticity (PLA) and local genetic variation (LOC) are both believed to play important roles in promoting range expansion. However, it is not clear which mechanism, PLA or LOC, contributes more to this process. According to our meta–analysis, PLA explained a higher proportion of adaptive phenotypic variation in most cases. Nevertheless, the predominance of an expansion mechanism depends on species characteristics and the trait studied. PLA may benefit from LOC to some extent. We suggest that the contribution of PLA to range expansion may better explain plant invasion success than the level of PLA itself.     

Can natural phenotypic variances be estimated reliably under homogeneous laboratory conditions?

The phenotypic variance is assumed to be greater in a more heterogeneous environment. The validity of this assumption is important for microevolutionists to extrapolate results from the laboratory to field environments. We subjected clutches of eggs from common snapping turtles (Chelydra serpentina) to a split-family design to evaluate the variability in incubation time and four size traits of neonates from eggs incubated in the laboratory and those left in situ. Mean size measurements were similar between the laboratory and the field, but incubation time was systematically longer in the field. We found no tendency among clutches for hatchlings resulting from eggs incubated in laboratory or field environments to demonstrate greater variability. Also contrary to expectation, clutches that experienced greater thermal variation in the field did not exhibit greater variation in phenotypic traits. Consequently, extrapolating results from the laboratory to the field may not always be problematic for microevolutionary analyses.     

Undermining the Baldwin expediting effect: does phenotypic plasticity accelerate evolution?

The claim that phenotypic plasticity speeds up evolution towards a target phenotype is a recent incarnation of the Baldwin effect. To differentiate this theory from earlier interpretations of Baldwin's ideas, we name it the Baldwin expediting effect. Models that demonstrate this effect assume an extreme fitness scenario which bestows high fitness upon a single optimal phenotype and treats all other phenotypes as equal. In two modeling frameworks, we demonstrate that the effects of plasticity on the rate of evolution are highly dependent on the fitness function and population starting conditions. We argue that phenotypic plasticity does not universally facilitate evolution. Furthermore, in cases where the Baldwin expediting effect occurs, it is not necessarily correlated with increased fitness and therefore is not sufficient to explain the evolutionary success of plasticity.     

When to rely on maternal effects and when on phenotypic plasticity?

Existing insight suggests that maternal effects have a substantial impact on evolution, yet these predictions assume that maternal effects themselves are evolutionarily constant. Hence, it is poorly understood how natural selection shapes maternal effects in different ecological circumstances. To overcome this, the current study derives an evolutionary model of maternal effects in a quantitative genetics context. In constant environments, we show that maternal effects evolve to slight negative values that result in a reduction of the phenotypic variance (canalization). By contrast, in populations experiencing abrupt change, maternal effects transiently evolve to positive values for many generations, facilitating the transmission of beneficial maternal phenotypes to offspring. In periodically fluctuating environments, maternal effects evolve according to the autocorrelation between maternal and offspring environments, favoring positive maternal effects when change is slow, and negative maternal effects when change is rapid. Generally, the strongest maternal effects occur for traits that experience very strong selection and for which plasticity is severely constrained. By contrast, for traits experiencing weak selection, phenotypic plasticity enhances the evolutionary scope of maternal effects, although maternal effects attain much smaller values throughout. As weak selection is common, finding substantial maternal influences on offspring phenotypes may be more challenging than anticipated.     

Convergent phenotypic evolution towards fosfomycin collateral sensitivity of Pseudomonas aeruginosa antibiotic-resistant mutants

The rise of antibiotic resistance and the reduced amount of novel antibiotics support the need of developing novel strategies to fight infections, based on improving the use of the antibiotics we already have. Collateral sensitivity is an evolutionary trade-off associated with the acquisition of antibiotic resistance that can be exploited to tackle this relevant health problem. However, different works have shown that patterns of collateral sensitivity are not always conserved, thus precluding the exploitation of this evolutionary trade-off to fight infections. In this work, we identify a robust pattern of collateral sensitivity to fosfomycin in Pseudomonas aeruginosa antibiotic-resistant mutants, selected by antibiotics belonging to different structural families. We characterize the underlying mechanism of the collateral sensitivity observed, which is a reduced expression of the genes encoding the peptidoglycan-recycling pathway, which preserves the peptidoglycan synthesis in situations where its de novo synthesis is blocked, and a reduced expression of fosA, encoding a fosfomycin-inactivating enzyme. We propose that the identification of robust collateral sensitivity patterns, as well as the understanding of the molecular mechanisms behind these phenotypes, would provide valuable information to design evolution-based strategies to treat bacterial infections.     

Will phenotypic plasticity affecting flowering phenology keep pace with climate change?

Rising temperatures have begun to shift flowering time, but it is unclear whether phenotypic plasticity can accommodate projected temperature change for this century. Evaluating clines in phenological traits and the extent and variation in plasticity can provide key information on assessing risk of maladaptation and developing strategies to mitigate climate change. In this study, flower phenology was examined in 52 populations of big sagebrush (Artemisia tridentata) growing in three common gardens. Flowering date (anthesis) varied 91 days from late July to late November among gardens. Mixed‐effects modeling explained 79% of variation in flowering date, of which 46% could be assigned to plasticity and genetic variation in plasticity and 33% to genetics (conditional R² = 0.79, marginal R² = 0.33). Two environmental variables that explained the genetic variation were photoperiod and the onset of spring, the Julian date of accumulating degree‐days >5 °C reaching 100. The genetic variation was mapped for contemporary and future climates (decades 2060 and 2090), showing flower date change varies considerably across the landscape. Plasticity was estimated to accommodate, on average, a ±13‐day change in flowering date. However, the examination of genetic variation in plasticity suggests that the magnitude of plasticity could be affected by variation in the sensitivity to photoperiod and temperature. In a warmer common garden, lower‐latitude populations have greater plasticity (+16 days) compared to higher‐latitude populations (+10 days). Mapped climatypes of flowering date for contemporary and future climates illustrate the wide breadth of plasticity and large geographic overlap. Our research highlights the importance of integrating information on genetic variation, phenotypic plasticity and climatic niche modeling to evaluate plant responses and elucidate vulnerabilities to climate change.     

Why are phenotypic mutation rates much higher than genotypic mutation rates?

The evolution of genotypic mutation rates has been investigated in numerous theoretical and experimental studies. Mutations, however, occur not only when copying DNA, but also when building the phenotype, especially when translating and transcribing DNA to RNA and protein. Here we study the effect of such phenotypic mutations. We find a maximum phenotypic mutation rate, umax, that is compatible with maintaining a certain function of the organism. This may be called a phenotypic error threshold. In particular, we find a minimum phenotypic mutation rate, umin, with the property that there is (nearly) no selection pressure to reduce the rate of phenotypic mutations below this value. If there is a cost for lowering the phenotypic mutation rate, then umin is close to the optimum phenotypic mutation rate that maximizes the fitness of the organism. In our model, there is selective pressure to decrease the rate of genotypic mutations to zero, but to decrease the rate of phenotypic mutations only to a positive value. Despite its simplicity, our model can explain part of the huge difference between genotypic and phenotypic mutation rates that is observed in nature. The relevant data are summarized.