Developmental Noise Research Articles

Effects of intrinsic environmental predictability on intra-individual and intra-population variability of plant reproductive traits and eco-evolutionary consequences.

It is widely accepted that changes in the environment affect mean trait expression, but little is known about how the environment shapes intra-individual and intra-population variance. Theory suggests that intra-individual variance might be plastic and under natural selection, rather than reflecting developmental noise, but evidence for this hypothesis is scarce. Here, we experimentally tested whether differences in intrinsic environmental predictability affect intra-individual and intra-population variability of different reproductive traits, and whether intra-individual variability is under selection. Under field conditions, we subjected Onobrychis viciifolia to more and less predictable precipitation over 4 generations and 4 years. We analysed effects on the coefficient of intra-individual variation (CVi-i) and the coefficient of intra-population variation (CVi-p), assessed whether the coefficients of intra-individual variation (CsVi-i) are under natural selection and tested for transgenerational responses (ancestor environmental effects on offspring). Less predictable precipitation led to higher CsVi-i and CsVi-p, consistent with plastic responses. The CsVi-i of all studied traits were under consistent stabilizing selection, and precipitation predictability affected the strength of selection and the location of the optimal CVi-i of a single trait. All CsVi-i differed from the optimal CVi-i and the maternal and offspring CsVi-i were positively correlated, showing that there was scope for change. Nevertheless, no consistent transgenerational effects were found in any of the three descendant generations, which contrasts with recent studies that detected rapid transgenerational responses in the trait means of different plant species. This suggests that changes in intra-individual variability take longer to evolve than changes in trait means, which may explain why high intra-individual variability is maintained, despite the stabilizing selection. The results indicate that plastic changes of intra-individual variability are an important determinant of whether plants will be able to cope with changes in environmental predictability induced by the currently observed climatic change.

Integrated early warning systems in marine bivalves reveal detrimental alterations of coastal habitats

Several biological levels are considered as signals of environmental perturbations so that integrative biological responses have been proposed in environmental monitoring activities. We evaluated the use of markers in Mytilus galloprovincialis at two different levels (protein nitration and S-nitrosylation, and geometric morphometrics) to investigate the sea coastal environmental status. We studied adductor muscle, digestive gland and valves of mussels collected from 3 sampling sites (2 disturbed + 1 control) in eastern Tyrrhenian Sea, and 2 (1 + 1) in western Ionian Sea. Molecular and morphometric markers showed significant variations in relation to environmental conditions, but the most interesting result was evidenced by the analysis of covariation between both protein post-translational modifications and geometric morphometric descriptors. The main interesting finding regards the relationship between protein nitration values (an irreversible molecular marker) of both adductor muscle and digestive gland, and geometric morphometric descriptors (that are Procrustes’ distances) of valve shapes. Molecular and morphometric markers revealed useful warning systems in detecting environmental changes, even if causes and mechanisms altering both cellular metabolism and shape morphology are still unclear. Our findings suggested that pollutants affected the normal cellular metabolic pathways altering the correct functionality at higher biological levels and producing developmental detrimental noise visible on the shell.

Are acute and acclimated thermal effects on metabolic rate modulated by cell size? A comparison between diploid and triploid zebrafish larvae.

Being composed of small cells may carry energetic costs related to maintaining ionic gradients across cell membranes as well as benefits related to diffusive oxygen uptake. Here, we test the hypothesis that these costs and benefits of cell size in ectotherms are temperature dependent. To study the consequences of cell size for whole-organism metabolic rate, we compared diploid and triploid zebrafish larvae differing in cell size. A fully factorial design was applied combining three different rearing and test temperatures that allowed us to distinguish acute from acclimated thermal effects. Individual oxygen consumption rates of diploid and triploid larvae across declining levels of oxygen availability were measured. We found that both acute and acclimated thermal effects affected the metabolic response. In comparison with triploids, diploids responded more strongly to acute temperatures, especially when reared at the highest temperature. These observations support the hypothesis that animals composed of smaller cells (i.e. diploids) are less vulnerable to oxygen limitation in warm aquatic habitats. Furthermore, we found slightly improved hypoxia tolerance in diploids. By contrast, warm-reared triploids had higher metabolic rates when they were tested at acute cold temperature, suggesting that being composed of larger cells may provide metabolic advantages in the cold. We offer two mechanisms as a potential explanation of this result, related to homeoviscous adaptation of membrane function and the mitigation of developmental noise. Our results suggest that being composed of larger cells provides metabolic advantages in cold water, while being composed of smaller cells provides metabolic advantages in warm water.

Effects of developmental noise exposure on inhibitory cell densities and perineuronal nets in A1 and AAF of mice

Within the auditory cortex, there are two primary-like regions considered to be ‘core’ cortical fields, the primary auditory cortex (A1) and the anterior auditory field (AAF). Both fields have sharp frequency tuning, tonotopic organization, and inputs from the ventral division of the medial geniculate body of the thalamus. AAF seems to be more specialized for faster spectrotemporal processing than A1, but the underlying mechanisms are unclear. A1 has been studied extensively in developmental plasticity, but how AAF changes with developmental experience is less clear. To address potential cellular correlates of processing differences between the two fields, we used immunohistochemistry to quantify the density of GABA, parvalbumin (PV), and somatostatin (SOM) cells in A1 and AAF of mice. We also compared the density of perineuronal nets (PNN) between A1 and AAF. PNNs are a specialized assembly of extracellular matrix involved in network maturation and plasticity. Finally, we compared the effects of developmental noise exposure on inhibitory and PNN cell density in these two core regions. In adult mice, there were more PV cells and PNNs surrounding cell bodies in AAF than in A1. Moderate level noise exposure during early development leads to 1) increased GABA and SOM cell density in both A1 and AAF, and 2) decreased PNN cell density in A1, but not AAF. Inhibitory cells without PNN appear to be more susceptible to changes following developmental noise exposure in both fields. Deep layers (5/6) are more susceptible to change in PNN density compared to superficial layers (1–4) of A1. Results are consistent with altered cortical gain control models and impaired maturation of cortex in response to noisy environments, and suggest that PNNs may be more prone to modification in A1 than AAF.

Developmental noise and ecological opportunity across space can release constraints on the evolution of plasticity.

Phenotypic plasticity is a potentially definitive solution to environment heterogeneity, driving biologists to understand why it is not ubiquitous in nature. While costs and constraints may limit the success of plasticity, we are still far from a complete theory of when these limitations actually proscribe adaptive plasticity. Here I use a simple model of plasticity incorporating developmental noise to explore the competitive and evolutionary relationships of specialist and generalist genotypes spreading across a heterogeneous landscape. Results show that plasticity can arise in the context of specialism, preadapting genotypes to later evolve toward plastic generalism. Developmental noise helps a mutant with imperfect plasticity successfully compete against its ancestor, providing an evolutionary path by which subsequent mutations can refine plasticity toward its optimum. These results address how the complex selection pressures across a heterogeneous environment can help evolution find paths around constraints arising from developmental mechanisms.

Isolating and quantifying the role of developmental noise in generating phenotypic variation.

Genotypic variation, environmental variation, and their interaction may produce variation in the developmental process and cause phenotypic differences among individuals. Developmental noise, which arises during development from stochasticity in cellular and molecular processes when genotype and environment are fixed, also contributes to phenotypic variation. While evolutionary biology has long focused on teasing apart the relative contribution of genes and environment to phenotypic variation, our understanding of the role of developmental noise has lagged due to technical difficulties in directly measuring the contribution of developmental noise. The influence of developmental noise is likely underestimated in studies of phenotypic variation due to intrinsic mechanisms within organisms that stabilize phenotypes and decrease variation. Since we are just beginning to appreciate the extent to which phenotypic variation due to stochasticity is potentially adaptive, the contribution of developmental noise to phenotypic variation must be separated and measured to fully understand its role in evolution. Here, we show that variation in the component of the developmental process corresponding to environmental and genetic factors (here treated together as a unit called the LALI-type) versus the contribution of developmental noise, can be distinguished for leopard gecko (Eublepharis macularius) head color patterns using mathematical simulations that model the role of random variation (corresponding to developmental noise) in patterning. Specifically, we modified the parameters of simulations corresponding to variation in the LALI-type to generate the full range of phenotypic variation in color pattern seen on the heads of eight leopard geckos. We observed that over the range of these parameters, variation in color pattern due to LALI-type variation exceeds that due to developmental noise in the studied gecko cohort. However, the effect of developmental noise on patterning is also substantial. Our approach addresses one of the major goals of evolutionary biology: to quantify the role of stochasticity in shaping phenotypic variation.

Phenotypic Plasticity, Developmental Instability, and Robustness: The Concepts and How They Are Connected

Developmental systems integrate inputs of variation from different origins into the observable variation of the resulting phenotype. Different components of phenotypic variation can be distinguished that correspond to those inputs, but the response of the system to each input factor can be modulated by other factors, so that there are interactions among the factors. This study uses a simplified developmental model of a trait to illustrate these interactions for genetic variation, phenotypic plasticity in response to temperature variation, and random developmental noise. The simulations show extensive interactions among the input factors, which can be explained by the nonlinear nature of the developmental model. These results are broadly consistent with results from actual biological systems.

Systemic signalling and local effectors in developmental stability, body symmetry, and size.

Symmetric growth and the origins of fluctuating asymmetry are unresolved phenomena of biology. Small, and sometimes noticeable, deviations from perfect bilateral symmetry reflect the vulnerability of development to perturbations. The degree of asymmetry is related to the magnitude of the perturbations and the ability of an individual to cope with them. As the left and right sides of an individual were presumed to be genetically identical, deviations of symmetry were traditionally attributed to non-genetic effects such as environmental and developmental noise. In this review, we draw attention to other possible sources of variability, especially to somatic mutations and transposons. Mutations are a major source of phenotypic variability and recent genomic data have highlighted somatic mutations as ubiquitous, even in phenotypically normal individuals. We discuss the importance of factors that are responsible for buffering and stabilizing the genome and for maintaining size robustness and quality through elimination of less-fit or damaged cells. However, the important question that arises from these studies is whether this self-correcting capacity and intrinsic organ size controls are sufficient to explain how symmetric structures can reach an identical size and shape. Indeed, recent discoveries in the fruit fly have uncovered a conserved hormone of the insulin/IGF/relaxin family, Dilp8, that is responsible for stabilizing body size and symmetry in the face of growth perturbations. Dilp8 alarm signals periphery growth status to the brain, where it acts on its receptor Lgr3. Loss of Dilp8-Lgr3 signaling renders flies incapable of detecting growth perturbations and thus maintaining a stable size and symmetry. These findings help to understand how size and symmetry of somatic tissues remain undeterred in noisy environments, after injury or illnesses, and in the presence of accumulated somatic mutations.

The asymmetry of dermatoglyphic finger ridge counts and the geographic altitude of the Jujenean population in northwest Argentina

Asymmetry is omnipresent in the living world and therefore is a measure of developmental noise and instability. The main stressing agent in high-altitude ecosystems is hypobaric hypoxia. The variation in bilateral dermatoglyphic symmetry in populations from the Province of Jujuy in northwest Argentina is analyzed, and these results are compared to those for other populations with different ethnic and environmental backgrounds. Fingerprints were collected from 310 healthy students (140 males and 170 females) aged 18–20 years from three localities in Jujuy Province—Abra Pampa (3484 m above sea level), Humahuaca (2939 m above sea level), and San Salvador de Jujuy (1260 m above sea level). Asymmetry by sex was assessed based on radial and ulnar ridge counts to determine its pattern of variability (directional asymmetry [DA], fluctuating asymmetry [FA] and antisymmetry), and asymmetry and diversity indices were calculated. A bivariate plot and principal component analysis (PCA) were used to compare these indices with those for other populations. Homogeneity was found between populations and sexes when radial and ulnar ridges were counted. FA values did not show significant differences by locality or side (ulnar and radial), but significant differences were found by finger and sex, with males showing significantly greater FA values. The asymmetry and diversity indices clearly group the Andean populations and separate them from populations of different ethnic and geographic origin. Only the diversity index showed significant differences by locality in males, which suggests a substantially different genetic component in Abra Pampa male samples.

Cyclin G and the Polycomb Repressive complexes PRC1 and PR-DUB cooperate for developmental stability.

In Drosophila, ubiquitous expression of a short Cyclin G isoform generates extreme developmental noise estimated by fluctuating asymmetry (FA), providing a model to tackle developmental stability. This transcriptional cyclin interacts with chromatin regulators of the Enhancer of Trithorax and Polycomb (ETP) and Polycomb families. This led us to investigate the importance of these interactions in developmental stability. Deregulation of Cyclin G highlights an organ intrinsic control of developmental noise, linked to the ETP-interacting domain, and enhanced by mutations in genes encoding members of the Polycomb Repressive complexes PRC1 and PR-DUB. Deep-sequencing of wing imaginal discs deregulating CycG reveals that high developmental noise correlates with up-regulation of genes involved in translation and down-regulation of genes involved in energy production. Most Cyclin G direct transcriptional targets are also direct targets of PRC1 and RNAPolII in the developing wing. Altogether, our results suggest that Cyclin G, PRC1 and PR-DUB cooperate for developmental stability.

Ultrastructural Alterations of Midgut Epithelium, But Not Greater Wing Fluctuating Asymmetry, in Paper Wasps (Polistes dominula) from Urban Environments.

Polistes paper wasps can be used to monitor trace metal contaminants, but the effects of pollution on the health of these insects are still unknown. We evaluated, in a south-eastern area of Spain, whether workers of Polistes dominula collected at urban and rural sites differ in health of midgut tissue and in fluctuating asymmetry, an estimate of developmental noise. We found that wasps collected at the urban sites had abundant lead (Pb)-containing spherites, which were less visible in wasps from the rural sites. Evident ultrastructural alterations in the epithelium of the midgut of the wasps collected at the urban sites included broken and disorganized microvilli, a high amount and density of heterochromatin in the nucleus of epithelial cells, cytoplasmic vacuolization and mitochondrial disruptions. Altogether, these findings suggest a negative effect on the transmembrane transport and a less efficient transcription. On the contrary, a healthy epithelium was observed in wasps from the rural sites. These differences may be preliminarily linked with levels of lead pollution, given that wasps from urban sites had double the Pb concentrations of wasps from rural sites. Level of fluctuating asymmetry was unrelated to wasp origin, thus suggesting no link between developmental noise and Pb-driven pollution.

Developmental pathways inferred from modularity, morphological integration and fluctuating asymmetry patterns in the human face

Facial asymmetries are usually measured and interpreted as proxies to developmental noise. However, analyses focused on its developmental and genetic architecture are scarce. To advance on this topic, studies based on a comprehensive and simultaneous analysis of modularity, morphological integration and facial asymmetries including both phenotypic and genomic information are needed. Here we explore several modularity hypotheses on a sample of Latin American mestizos, in order to test if modularity and integration patterns differ across several genomic ancestry backgrounds. To do so, 4104 individuals were analyzed using 3D photogrammetry reconstructions and a set of 34 facial landmarks placed on each individual. We found a pattern of modularity and integration that is conserved across sub-samples differing in their genomic ancestry background. Specifically, a signal of modularity based on functional demands and organization of the face is regularly observed across the whole sample. Our results shed more light on previous evidence obtained from Genome Wide Association Studies performed on the same samples, indicating the action of different genomic regions contributing to the expression of the nose and mouth facial phenotypes. Our results also indicate that large samples including phenotypic and genomic metadata enable a better understanding of the developmental and genetic architecture of craniofacial phenotypes.

Life Is an N of 1

Life Is an N of 1

Fluctuating asymmetry of meristic traits: an isofemale line analysis in an invasive drosophilid, Zaprionus indianus.

Metric (e.g., body size) and meristic (e.g., bristle number) traits are of general use in quantitative genetic studies, and the phenotypic variance is subdivided into a genetic and a non-genetic environmental component. The non-genetic variance may have two origins: a common garden effect between individuals and a developmental instability within the same individual. Developmental instability may be studied by considering the fluctuating asymmetry (FA) between the two sides of the body. The isofemale line technique is a convenient method for investigating the architecture of natural populations but has been rarely implemented for investigating FA. In this paper, we use this experimental design for analyzing four meristic traits in eight populations of the cosmopolitan Zaprionus indianus. A study of the correlation between left and right side of each line revealed that almost 90% of the variability was due to a developmental noise, while a much higher correlation among the means of the lines from the same population was observed. A slight trend toward a directional asymmetry was observed: more thoracic bristles on the left side. Four kinds of indices, scaled or non-scaled to the mean were used for comparing the different traits. Unscaled values (mean absolute values or standard deviation of each line) revealed a linear increase with the means. Interestingly the results of ovariole number were included in the same regression. With the scaled indices (mean absolute divided by each individual value or stadard deviation devided by the mean), the differences among traits were considerably decreased, but still remained significant. The mean FA of the various traits were not correlated, suggesting that each trait harbors its own developmental stability. The CVs of FA were high with a magnitude similar to those of the trait themselves, slightly less than 10%. Finally, even with the isofemale line design, which is a powerful means for unravelling slight genetic variations, we did not to find any clear indication of a genetic component of FA under the optimal environmental conditions used in this study.

Asymmetry in dentition and shape of pharyngeal arches in the clonal fish Chrosomus eos-neogaeus: Phenotypic plasticity and developmental instability.

The effect of the environment may result in different developmental outcomes. Extrinsic signals can modify developmental pathways and result in alternative phenotypes (phenotypic plasticity). The environment can also be interpreted as a stressor and increase developmental instability (developmental noise). Directional and fluctuating asymmetry provide a conceptual background to discriminate between these results. This study aims at assessing whether variation in dentition and shape of pharyngeal arches of the clonal fish Chrosomus eos-neogaeus results from developmental instability or environmentally induced changes. A total of 262 specimens of the Chrosomus eos-neogaeus complex from 12 natural sites were analysed. X-ray microcomputed tomography (X-ray micro-CT) was used to visualize the pharyngeal arches in situ with high resolution. Variation in the number of pharyngeal teeth is high in hybrids in contrast to the relative stability observed in both parental species. The basal dental formula is symmetric while the most frequent alternative dental formula is asymmetric. Within one lineage, large variation in the proportion of individuals bearing basal or alternative dental formulae was observed among sites in the absence of genetic difference. Both dentition and arch shape of this hybrid lineage were explained significantly by environmental differences. Only individuals bearing asymmetric dental formula displayed fluctuating asymmetry as well as directional left-right asymmetry for the arches. The hybrids appeared sensitive to environmental signals and intraspecific variation on pharyngeal teeth was not random but reflects phenotypic plasticity. Altogether, these results support the influence of the environment as a trigger for an alternative developmental pathway resulting in left-right asymmetry in dentition and shape of pharyngeal arches.

Fluctuating Asymmetry of Human Populations: A Review

Fluctuating asymmetry, the random deviation from perfect symmetry, is a widely used population-level index of developmental instability, developmental noise, and robustness. It reflects a population’s state of adaptation and genomic coadaptation. Here, we review the literature on fluctuating asymmetry of human populations. The most widely used bilateral traits include skeletal, dental, and facial dimensions; dermatoglyphic patterns and ridge counts; and facial shape. Each trait has its advantages and disadvantages, but results are most robust when multiple traits are combined into a composite index of fluctuating asymmetry (CFA). Both environmental (diet, climate, toxins) and genetic (aneuploidy, heterozygosity, inbreeding) stressors have been linked to population-level variation in fluctuating asymmetry. In general, these stressors increase average fluctuating asymmetry. Nevertheless, there have been many conflicting results, in part because (1) fluctuating asymmetry is a weak signal in a sea of noise; and (2) studies of human fluctuating asymmetry have not always followed best practices. The most serious concerns are insensitive asymmetry indices (correlation coefficient and coefficient of indetermination), inappropriate size scaling, unrecognized mixture distributions, inappropriate corrections for directional asymmetry, failure to use composite indices, and inattention to measurement error. Consequently, it is often difficult (or impossible) to compare results across traits, and across studies.

Multivariate sexual selection on male tegmina in wild populations of sagebrush crickets, Cyphoderris strepitans (Orthoptera: Haglidae).

Although the strength and form of sexual selection on song in male crickets have been studied extensively, few studies have examined selection on the morphological structures that underlie variation in males' song, particularly in wild populations. Geometric morphometric techniques were used to measure sexual selection on the shape, size and symmetry of both top and bottom tegmina in wild populations of sagebrush crickets, a species in which nuptial feeding by females imposes an unambiguous phenotypic marker on males. The size of the tegmina negatively covaried with song dominant frequency and positively covaried with song pulse duration. Sexual selection was more intense on the bottom tegmen, conceivably because it interacts more freely with the subtegminal airspace, which may play a role in song amplification. An expanded coastal/subcostal region was one of the phenotypes strongly favoured by disruptive selection on the bottom tegmen, an adaptation that may form a more effective seal with the thorax to prevent noise cancellation. Directional selection also favoured increased symmetry in tegminal shape. Assuming more symmetrical males are better able to buffer against developmental noise, the song produced by these males may make them more attractive to females. Despite the strong stabilizing selection documented previously on the dominant frequency of the song, stabilizing selection on the resonator that regulates dominant frequency was surprisingly absent. Nonetheless, wing morphology had an important influence on song structure and appears to be subject to significant linear and nonlinear sexual selection through female mate choice.

Random sex determination: When developmental noise tips the sex balance.

Sex-determining factors are usually assumed to be either genetic or environmental. The present paper aims at drawing attention to the potential contribution of developmental noise, an important but often-neglected component of phenotypic variance. Mutual inhibitions between male and female pathways make sex a bistable equilibrium, such that random fluctuations in the expression of genes at the top of the cascade are sufficient to drive individual development toward one or the other stable state. Evolutionary modeling shows that stochastic sex determinants should resist elimination by genetic or environmental sex determinants under ecologically meaningful settings. On the empirical side, many sex-determination systems traditionally considered as environmental or polygenic actually provide evidence for large components of stochasticity. In reviewing the field, I argue that sex-determination systems should be considered within a three-ends continuum, rather than the classical two-ends continuum.

Can a Network Approach Resolve How Adaptive vs Nonadaptive Plasticity Impacts Evolutionary Trajectories?

Theoretical and empirical work has described a range of scenarios in which plasticity may shape adaptation to a novel environment. For example, recent studies have implicated a role for both adaptive and non-adaptive plasticity in facilitating adaptive evolution, yet we lack a broad mechanistic framework to predict under what conditions each scenario is likely to dominate evolutionary processes. We propose that such a framework requires understanding how transcriptional, protein, and developmental networks change in response to different rearing environments across evolutionary time scales. Our central argument is that these hierarchical networks generate and maintain phenotypic variation in populations, both by buffering organisms from developmental noise and mutational inputs and by exhibiting flexible responses to environmental cues. These network properties in turn lead to predictions about how plasticity should influence adaptive evolution. Because buffering mechanisms allow the build-up of cryptic genetic variation (i.e., genetic variation without phenotypic consequences), the initial response of individuals colonizing novel environments should be a release of genetic and phenotypic variation that selection acts upon; some of which is adaptive and some of which is not. Thus, in the early stages of adaptation, strong selection against maladaptive phenotypes should result in rapid evolution acting on standing cryptic variation. However, over longer time scales, evolutionary change should largely be compensatory, to rebuild robust developmental processes and promote integrated phenotypes. We argue that considering how hierarchical networks respond over developmental and evolutionary time encompasses a more mechanistic understanding of the genotype-phenotype map, and will result in a more predictive framework for understanding the role of plasticity in adaptive evolution.

HSP90 canonical content organizes a molecular scaffold mechanism to progress flowering.

Highly interactive signaling processes constitute a set of parameters intertwining in a continuum mode to shape body formation and development. A sophisticated gene network is required to integrate environmental and endogenous cues in order to modulate flowering. However, the molecular mechanisms that coordinate the circuitries of flowering genes remain unclear. Here using complemented experimental approaches, we uncover the decisive and essential role of HEAT SHOCK PROTEIN 90 (HSP90) in restraining developmental noise to an acceptable limit. Localized depletion of HSP90 mRNAs in the shoot apex resulted in low penetrance of vegetative-to-reproductive phase transition and completely abolished flower formation. Extreme variation in expression of flowering genes was also observed in HSP90 mRNA-depleted transformed plants. Transient heat-shock treatments moderately increased HSP90 mRNA levels and rescued flower arrest. The offspring had a low, nevertheless noticeable failure to promote transition from vegetative into the reproductive phase and showed flower morphological heterogeneity. In floral tissues a moderate variation in HSP90 transcript levels and in the expression of flowering genes was detected. Key flowering proteins comprised clientele of the molecular chaperone demonstrating that the HSP90 is essential during vegetative-to-reproductive phase transition and flower development. Our results uncover that HSP90 consolidates a molecular scaffold able to arrange and organize flowering gene network and protein circuitry, and effectively counterbalance the extent to which developmental noise perturbs phenotypic traits.