Reproductive functions of kisspeptin and Gpr54 across the life cycle of mice and men

The reproductive phenotypes of nearly two dozen patients with mutations in GPR54 have been reported, as have the phenotypes of four mouse lines mutant for Gpr54 and two lines mutant for Kiss1. These phenotypes demonstrate that kisspeptin/Gpr54 function is required at all phases of the life cycle when the secretion of gonadotropin-releasing hormone (GnRH) is robust. Furthermore, there is phenotypic variability ranging from severe hypogonadism to partial sexual development. Collectively, these findings suggest that kisspeptin and Gpr54 serve as an essential conduit for relaying developmental information to the GnRH neuron.     

THE EVOLUTION OF PHENOTYPIC CORRELATIONS AND “DEVELOPMENTAL MEMORY”

Development introduces structured correlations among traits that may constrain or bias the distribution of phenotypes produced. Moreover, when suitable heritable variation exists, natural selection may alter such constraints and correlations, affecting the phenotypic variation available to subsequent selection. However, exactly how the distribution of phenotypes produced by complex developmental systems can be shaped by past selective environments is poorly understood. Here we investigate the evolution of a network of recurrent nonlinear ontogenetic interactions, such as a gene regulation network, in various selective scenarios. We find that evolved networks of this type can exhibit several phenomena that are familiar in cognitive learning systems. These include formation of a distributed associative memory that can “store” and “recall” multiple phenotypes that have been selected in the past, recreate complete adult phenotypic patterns accurately from partial or corrupted embryonic phenotypes, and “generalize” (by exploiting evolved developmental modules) to produce new combinations of phenotypic features. We show that these surprising behaviors follow from an equivalence between the action of natural selection on phenotypic correlations and associative learning, well‐understood in the context of neural networks. This helps to explain how development facilitates the evolution of high‐fitness phenotypes and how this ability changes over evolutionary time.     

Iterative development and the scope for plasticity: contrasts among trait categories in an adaptive radiation

Phenotypic plasticity can influence evolutionary change in a lineage, ranging from facilitation of population persistence in a novel environment to directing the patterns of evolutionary change. As the specific nature of plasticity can impact evolutionary consequences, it is essential to consider how plasticity is manifested if we are to understand the contribution of plasticity to phenotypic evolution. Most morphological traits are developmentally plastic, irreversible, and generally considered to be costly, at least when the resultant phenotype is mis-matched to the environment. At the other extreme, behavioral phenotypes are typically activational (modifiable on very short time scales), and not immediately costly as they are produced by constitutive neural networks. Although patterns of morphological and behavioral plasticity are often compared, patterns of plasticity of life history phenotypes are rarely considered. Here we review patterns of plasticity in these trait categories within and among populations, comprising the adaptive radiation of the threespine stickleback fish Gasterosteus aculeatus. We immediately found it necessary to consider the possibility of iterated development, the concept that behavioral and life history trajectories can be repeatedly reset on activational (usually behavior) or developmental (usually life history) time frames, offering fine tuning of the response to environmental context. Morphology in stickleback is primarily reset only in that developmental trajectories can be altered as environments change over the course of development. As anticipated, the boundaries between the trait categories are not clear and are likely to be linked by shared, underlying physiological and genetic systems.     

Temperature-Dependent Expression of the APTEROUS Phenotype in DROSOPHILA MELANOGASTER

Mutations at the apterous (ap) locus in Drosophila melanogaster produce a variety of developmental defects, including several classes of wing abnormalities. We describe the wing phenotype produced by homozygotes and hemizygotes of three different temperature-sensitive apterous alleles grown at 16, 18, 20, 22, 25, and 29 degrees. We also describe the phenotype produced by each of these three alleles when heteroallelic with the non-temperature-sensitive apc allele. Constant-temperature and temperature-shift experiments show that each of the heteroallelic genotypes can produce several of the previously described apterous phenotypes and that the length of the temperature-sensitive period for a given phenotype depends on the allelic combinations used to measure it. We suggest that the stage-specific requirements of the tissue for gene product, rather than the time of gene expression per se, determine the temperature-sensitive periods for apterous and other loci. The results support the hypothesis that the various wing phenotypes produced by apterous mutations are due to quantitative reductions in the activity of gene product and that failure to meet specific threshold requirements for gene product can lead to qualitatively different phenotypes.     

Developmental Genetics of Loci at the Base of the X Chromosome of Drosophila Melanogaster

We have conducted a genetic and developmental analysis of the 26 contiguous genetic complementation groups within the 19D3-20F2 interval of the base of the X chromosome, a region of 34 polytene bands delimited by the maroon-like and suppressor of forked loci. Within this region there are four loci which cause visible phenotypes but which have little or no effect on zygotic viability (maroon-like, little fly, small optic lobes and sluggish). There are 22 loci which, when mutated, are zygotic lethals and three of these, legless/runt, folded gastrulation and 13E3, have severe effects on embryonic development. In addition, three visible phenotypes have been defined only by overlapping deficiencies (melanized-like, tumorous head, and varied outspread). We have analyzed the lethal phases and maternal requirement of 58 mutations at 22 of the zygotic lethal loci by means of germline clone analysis using the dominant female sterile technique. Additionally, all lethal complementation groups, as well as a specific subset of deficiencies, have been studied histologically for defects in the development of the central and peripheral embryonic nervous systems.     

Pathological axes of wound repair: Gastrulation revisited

Post-traumatic inflammation is formed by molecular and cellular complex mechanisms whose final goal seems to be injured tissue regeneration. In the skin -an exterior organ of the body- mechanical or thermal injury induces the expression of different inflammatory phenotypes that resemble similar phenotypes expressed during embryo development. Particularly, molecular and cellular mechanisms involved in gastrulation return. This is a developmental phase that delineates the three embryonic germ layers: ectoderm, endoderm and mesoderm. Consequently, in the post-natal wounded skin, primitive functions related with the embryonic mesoderm, i.e. amniotic and yolk sac-derived, are expressed. Neurogenesis and hematogenesis stand out among the primitive function mechanisms involved. Interestingly, in these phases of the inflammatory response, whose molecular and cellular mechanisms are considered as traces of the early phases of the embryonic development, the mast cell, a cell that is supposedly inflammatory, plays a key role. The correlation that can be established between the embryonic and the inflammatory events suggests that the results obtained from the research regarding both great fields of knowledge must be interchangeable to obtain the maximum advantage.     

Genetic variation in developmental times among four pure lines exhibiting specific wing form and body color in the brown planthopper, <Emphasis Type="Italic">Nilaparvata lugens</Emphasis> (Hemiptera: Auchenorrhyncha)

Developmental times were compared among four pure lines of wing-dimorphic Nilaparvata lugens generated by successive selections for the following designated characteristics: blackish short-winged (BS), blackish long-winged (BL), yellowish brown short-winged (YS) and yellowish brown long-winged (YL). When the nymphs were reared on rice seedlings at low density, the developmental time was in the order of BS = BL < YS = YL, while with an increase in rearing density, the time lengthened markedly in long-winged lines but only slightly in short-winged lines, rearranging the order to BS < BL = YS < YL. Among F₁ progeny of BS × YL, the developmental time in short-winged phenotypes was the same as those of BS lines at any of the densities tested, but the long-winged phenotypes emerged as adults at intermediate time between BS and YL lines at high density. This method of inheritance of developmental time and the differences in the duration observed among the four pure lines suggest that the genes regulating wing form and body color expression are also involved in the regulation of developmental time.     

Developmental palaeontology in synapsids: the fossil record of ontogeny in mammals and their closest relatives

The study of fossilized ontogenies in mammals is mostly restricted to postnatal and late stages of growth, but nevertheless can deliver great insights into life history and evolutionary mechanisms affecting all aspects of development. Fossils provide evidence of developmental plasticity determined by ecological factors, as when allometric relations are modified in species which invaded a new space with a very different selection regime. This is the case of dwarfing and gigantism evolution in islands. Skeletochronological studies are restricted to the examination of growth marks mostly in the cement and dentine of teeth and can provide absolute age estimates. These, together with dental replacement data considered in a phylogenetic context, provide life-history information such as maturation time and longevity. Palaeohistology and dental replacement data document the more or less gradual but also convergent evolution of mammalian growth features during early synapsid evolution. Adult phenotypes of extinct mammals can inform developmental processes by showing a combination of features or levels of integration unrecorded in living species. Some adult features such as vertebral number, easily recorded in fossils, provide indirect information about somitogenesis and hox-gene expression boundaries. Developmental palaeontology is relevant for the discourse of ecological developmental biology, an area of research where features of growth and variation are fundamental and accessible among fossil mammals.     

Modification of developmental instability and fitness: Malathion-resistance in the Australian sheep blowfly,Lucilia cuprina

The evolution of resistance to malathion byLucilia cuprina initially results in an increase in fluctuating asymmetry. Resistant flies are at a selective disadvantage, relative to susceptibles, in the absence of the insecticide. A fitness/asymmetry modifier of diazinon-resistant phenotypes ameliorates these effects resulting in malathion-resistant phenotypes of relative fitness and asymmetry similar to susceptibles. For the nine genotypic combinations of the modifier and malathion-resistance alleles, developmental time increases linearly with increasing asymmetry. Percentage egg hatch decreases linearly with increasing asymmetry. The initially disruptive effect of the malathion-resistant allele was partially dominant, the effect of the modifier dominant. The results are discussed in terms of developmental perturbation, asymmetry estimation and relative fitness to consider whether it is adequate to use changes in fluctuating asymmetry alone as measures of developmental instability. It is suggested that in some circumstances antisymmetry may indicate developmental instability and that the diazinon/malathion-resistance systems inL. cuprina may allow the relative importance of genetical and/or environmental developmental perturbations to be ascertained.     

Xenopus as a model organism in developmental chemical genetic screens

Chemical genetics is a potentially powerful tool for studying developmental processes in vertebrate systems. We present data showing Xenopus laevis as a model organism in which systematic chemical genetic screens can be carried out. Previous forward chemical genetic screens, including those with developing zebrafish embryos, have demonstrated the nature and value of biological information gained with this approach. We show how amenable Xenopus is to chemical genetics by investigating a series of compounds either with known biochemical effects, or previously identified to give developmental phenotypes, on a range of biological functions, including the development of pigmentation, the heart and the central nervous system in zebrafish. We have found that the compounds give comparable phenotypes when applied to developing Xenopus embryos. We have also studied the penetrance and expressivity of these chemical genetic phenotypes in relation to genetic variation and the developmental window during which the compound is present. Finally, we assess the feasibility and the potential throughput of a screen in this vertebrate species.     

Neophenogenesis: a developmental theory of phenotypic evolution

An important task for evolutionary biology is to explain how phenotypes change over evolutionary time. Neo-Darwinian theory explains phenotypic change as the outcome of genetic change brought about by natural selection. In the neo-Darwinian account, genetic change is primary; phenotypic change is a secondary outcome that is often given no explicit consideration at all. In this article, we introduce the concept of neophenogenesis: a persistent, transgenerational change in phenotypes over evolutionary time. A theory of neophenogenesis must encompass all sources of such phenotypic change, not just genetic ones. Both genetic and extra-genetic contributions to neophenogenesis have their effect through the mechanisms of development, and developmental considerations, particularly a rejection of the commonly held distinction between inherited and acquired traits, occupy a central place in neophenogenetic theory. New phenotypes arise because of a change in the patterns of organism-environment interaction that produce development in members of a population. So long as these new patterns of developmental interaction persist, the new phenotype(s) will also persist. Although the developmental mechanisms that produce the novel phenotype may change, as in the process known as "genetic assimilation", such changes are not necessary in order for neophenogenesis to occur, because neophenogenetic theory is a theory of phenotypic, not genetic, change.     

SEASONALITY MAINTAINS ALTERNATIVE LIFE‐HISTORY PHENOTYPES

Many organisms express discrete alternative phenotypes (polyphenisms) in relation to predictable environmental variation. However, the evolution of alternative life‐history phenotypes remains poorly understood. Here, we analyze the evolution of alternative life histories in seasonal environments by using temperate insects as a model system. Temperate insects express alternative developmental pathways of diapause and direct development, the induction of a certain pathway affecting fitness through its life‐history correlates. We develop a methodologically novel and holistic simulation model and optimize development time, growth rate, body size, reproductive effort, and adult life span simultaneously in both developmental pathways. The model predicts that direct development should be associated with shorter development time (duration of growth) and adult life span, higher growth rate and reproductive effort, smaller body size as well as lower fecundity compared to the diapause pathway, because the two generations divide the available time unequally. These predictions are consistent with many empirical data. Our analysis shows that seasonality alone can explain the evolution of alternative life histories.     

Photoperiod–temperature phase lag: A universal environmental context of seasonal developmental plasticity

Seasonal developmental plasticity, which consists of season-dependent alternations of developmental processes, has evolved to produce optimal phenotypes depending on specific periods in a year. For example, many phenological events in plants, such as flowering, fruiting, bud blast, bud formation, and growth cessation, are often controlled seasonally. Although temperature and photoperiod are the two major seasonal cues for such responses, the importance of phase lag between annual oscillations of the two signals has been unexplored, despite its universal nature in the context of seasonal environments. In this article, the phase-lag calendar hypothesis (New Phytologist, 210, 2016, 399), especially the one between temperature and photoperiod, is explained using meteorological data obtained from central Japan as an example. We set forth to show how, for a narrow window in time of a couple of weeks in a year, simple threshold responses to these two signals that differ in annual oscillation phases are enough to make developmental plasticity to be expressed as phenological events. The properties of the underlying mechanisms of the events in different seasons are further predicted, and the responses are compared with reported empirical examples. Because many organisms have evolved under the phase lag between photoperiod and temperature, the developmental plasticity in response to the phase lag should be evaluated for diverse organisms.     

Evolution and molecular mechanisms of adaptive developmental plasticity

Aside from its selective role in filtering inter-individual variation during evolution by natural selection, the environment also plays an instructive role in producing variation during development. External environmental cues can influence developmental rates and/or trajectories and lead to the production of distinct phenotypes from the same genotype. This can result in a better match between adult phenotype and selective environment and thus represents a potential solution to problems posed by environmental fluctuation. The phenomenon is called adaptive developmental plasticity. The study of developmental plasticity integrates different disciplines (notably ecology and developmental biology) and analyses at all levels of biological organization, from the molecular regulation of changes in organismal development to variation in phenotypes and fitness in natural populations. Here, we focus on recent advances and examples from morphological traits in animals to provide a broad overview covering (i) the evolution of developmental plasticity, as well as its relevance to adaptive evolution, (ii) the ecological significance of alternative environmentally induced phenotypes, and the way the external environment can affect development to produce them, (iii) the molecular mechanisms underlying developmental plasticity, with emphasis on the contribution of genetic, physiological and epigenetic factors, and (iv) current challenges and trends, including the relevance of the environmental sensitivity of development to studies in ecological developmental biology, biomedicine and conservation biology.     

THE EVOLUTION OF CANALIZATION AND THE BREAKING OF VON BAER'S LAWS: MODELING THE EVOLUTION OF DEVELOPMENT WITH EPISTASIS

Evolution can change the developmental processes underlying a character without changing the average expression of the character itself. This sort of change must occur in both the evolution of canalization, in which a character becomes increasingly buffered against genetic or developmental variation, and in the phenomenon of closely related species that show similar adult phenotypes but different underlying developmental patterns. To study such phenomena, I develop a model that follows evolution on a surface representing adult phenotype as a function of underlying developmental characters. A contour on such a “phenotype landscape” is a set of states of developmental characters that produce the same adult phenotype. Epistasis induces curvature of this surface, and degree of canalization is represented by the slope along a contour. I first discuss the geometric properties of phenotype landscapes, relating epistasis to canalization. I then impose a fitness function on the phenotype and model evolution of developmental characters as a function of the fitness function and the local geometry of the surface. This model shows how canalization evolves as a population approaches an optimum phenotype. It further shows that under some circumstances, “decanalization” can occur, in which the expression of adult phenotype becomes increasingly sensitive to developmental variation. This process can cause very similar populations to diverge from one another developmentally even when their adult phenotypes experience identical selection regimes.     

On the Evolutionary Developmental Biology of Speciation

The mainstream approaches to the study of speciation and clade diversification have extensively focused on genetic mechanisms and ecological contexts, while much less attention has been paid to the role of development. In this paper we provide materials to support the thesis that taking development into the picture of evolutionary processes can bring important insights on how species multiply and diversify. Evidence that developmentally entangled evolutionary factors are important in speciation comes from different lines of investigation that can be broadly grouped under three headings: evolvability, phenotypic plasticity, and phenology. Evolvability enters the scene through the complexity of the genotype-phenotype map, the developmental link between transmissible genetic information and selectable phenotypes. Phenotypic plasticity can act as a facilitator for speciation, promoting diversification at different stages of the speciation process, as well as generating novel targets and novel trade-offs for evolutionary processes. The formal inclusion of the developmental time axis in speciation models widens the scope for investigating the onset and/or reinforcement of reproductive barriers through a range of situations along an organism??s life cycle. Overall, developmental processes can contribute to speciation and diversification at different stages of the speciation process, at different levels of biological organization and along the organism??s whole life cycle.     

Pleiotropic signaling pathways orchestrate yeast development

Developmental phenotypes in Saccharomyces cerevisiae and related yeasts include responses such as filamentous growth, sporulation, and the formation of biofilms and complex colonies. These developmental phenotypes are regulated by evolutionarily conserved, nutrient-responsive signaling networks. The signaling mechanisms that control development in yeast are highly pleiotropic--all the known pathways contribute to the regulation of multiple developmental outcomes. This degree of pleiotropy implies that perturbations of these signaling pathways, whether genetic, biochemical, or environmentally induced, can manifest in multiple (and sometimes unexpected) ways. We summarize the current state of knowledge of developmental pleiotropy in yeast and discuss its implications for understanding functional relationships.     

Cryptic variation in butterfly eyespot development: the importance of sample size in gene expression studies

Previous studies have shown that development can be robust to variation in parameters such as the timing or level of gene expression. This leads to the prediction that natural populations should be able to host developmental variation that has little phenotypic effect. Cryptic variation is of particular interest because it can result in selectable phenotypes when "released" by environmental or genetic factors. Currently, however, we have little idea of how variation is distributed between genes or over time in pattern formation processes. Here we survey expression of Notch (N), Spalt (Sal), and Engrailed (En) during butterfly eyespot determination to better understand how pattern formation may vary within a population. We observed substantial heterochronic variance in the progress of spatial expression patterns for all three proteins, suggesting some degree of developmental buffering in eyespot development. Peak variance for different proteins was found at both early and late stages of development, contrasting with previous models suggesting that the distribution of variance should be more temporally focused during pattern formation. We speculate that our observations are representative of a standing reservoir of cryptic variation that may contribute to phenotypic evolution under certain circumstances. Our results also provide a strong cautionary message that gene expression studies with limited sample sizes can be positively misleading in terms of inferring expression pattern time series, as well as for making cross-species phylogenetic comparisons.