Tales of the cryptic: unveiling more angiogenesis inhibitors

Over the past few years, there has been a dramatic increase in the identification of anti-angiogenic fragments from larger proteins with unrelated functions. These cryptic anti-angiogenic molecules are largely derived from matrix components such as collagen and fibronectin, as well as from circulating proteins and some intracellular proteins. Here, we discuss the relevance of these developments in terms of their physiological roles and possible therapeutic applications.     

Diet and hormonal manipulation reveal cryptic genetic variation: implications for the evolution of novel feeding strategies

When experiencing resource competition or abrupt environmental change, animals often must transition rapidly from an ancestral diet to a novel, derived diet. Yet, little is known about the proximate mechanisms that mediate such rapid evolutionary transitions. Here, we investigated the role of diet-induced, cryptic genetic variation in facilitating the evolution of novel resource-use traits that are associated with a new feeding strategy—carnivory—in tadpoles of spadefoot toads (genus Spea). We specifically asked whether such variation in trophic morphology and fitness is present in Scaphiopus couchii, a species that serves as a proxy for ancestral Spea. We also asked whether corticosterone, a vertebrate hormone produced in response to environmental signals, mediates the expression of this variation. Specifically, we compared broad-sense heritabilities of tadpoles fed different diets or treated with exogenous corticosterone, and found that novel diets can expose cryptic genetic variation to selection, and that diet-induced hormones may play a role in revealing this variation. Our results therefore suggest that cryptic genetic variation may have enabled the evolutionary transition to carnivory in Spea tadpoles, and that such variation might generally facilitate rapid evolutionary transitions to novel diets.     

Maintenance of genetic variation in phenotypic plasticity: the role of environmental variation

We study genetic variation in phenotypic plasticity maintained by a balance between mutation and weak stabilizing selection. We consider linear reaction norms allowing for spatial and/or temporal variation in the environments of development and selection. We show that the overall genetic variation maintained does not depend on whether the trait is plastic or not. The genetic variances in height and slope of a linear reaction norm, and their covariance, are predicted to decrease with the variation in the environment. Non-pleiotropic loci influencing either height or slope are expected to decrease the genetic variance in slope relative to that in height. Decrease in the ratio of genetic variance in slope to genetic variance in height with increasing variation in the environment presents a test for the presence of loci that only influence the slope, and not the height. We use data on Drosophila to test the theory. In seven of eight pair-wise comparisons genetic variation in reaction norm is higher in a less variable environment than in a more variable environment, which is in accord with the model's predictions.     

Developmental and genetic origins of murine long bone length variation

If we wish to understand whether development influences the rate or direction of morphological evolution, we must first understand the developmental bases of morphological variation within species. However, quantitative variation in adult morphology is the product of molecular and cellular processes unfolding from embryonic development through juvenile growth to maturity. The Atchley-Hall model provides a useful framework for dissecting complex morphologies into their component parts as a way of determining which developmental processes contribute to variation in adult form. We have examined differences in postnatal allometry and the patterns of genetic correlation between age-specific traits for ten recombinant inbred strains of mice generated from an intercross of LG/J and SM/J. Long bone length is closely tied to body size, but variation in adult morphology is more closely tied to differences in growth rate between 3 and 5 weeks of age. These analyses show that variation generated during early development is overridden by variation generated later in life. To more precisely determine the cellular processes generating this variation we then examined the cellular dynamics of long bone growth plates at the time of maximum elongation rate differences in the parent strains. Our analyses revealed that variation in long bone length is the result of faster elongation rates of the LG/J stain. The developmental bases for these differences in growth rate involve the rate of cell division and chondrocyte hypertrophy in the growth plate.     

Developmental genetic evidence for a monophyletic origin of the bilaterian brain

The widely held notion of an independent evolutionary origin of invertebrate and vertebrate brains is based on classical phylogenetic, neuroanatomical and embryological data. The interpretation of these data in favour of a polyphyletic origin of animals brains is currently being challenged by three fundamental findings that derive from comparative molecular, genetic and developmental analyses. First, modern molecular systematics indicates that none of the extant animals correspond to evolutionary intermediates between the protostomes and the deuterostomes, thus making it impossible to deduce the morphological organization of the ancestral bilaterian or its brain from living species. Second, recent molecular genetic evidence for the body axis inversion hypothesis now supports the idea that the basic body plan of vertebrates and invertebrates is similar but inverted, suggesting that the ventral nerve chord of protostome invertebrates is homologous to the dorsal nerve cord of deuterostome chordates. Third, a developmental genetic analysis of the molecular control elements involved in early embryonic brain patterning is uncovering the existence of structurally and functionally homologous genes that have comparable and interchangeable functions in key aspects of brain development in invertebrate and vertebrate model systems. All three of these findings are compatible with the hypothesis of a monophyletic origin of the bilaterian brain. Here we review these findings and consider their significance and implications for current thinking on the evolutionary origin of bilaterian brains. We also preview the impact of comparative functional genomic analyses on our understanding of brain evolution.     

A heuristic model on the role of plasticity in adaptive evolution: plasticity increases adaptation,population viability and genetic variation

An ongoing new synthesis in evolutionary theory is expanding our view of the sources of heritable variation beyond point mutations of fixed phenotypic effects to include environmentally sensitive changes in gene regulation. This expansion of the paradigm is necessary given ample evidence for a heritable ability to alter gene expression in response to environmental cues. In consequence, single genotypes are often capable of adaptively expressing different phenotypes in different environments, i.e. are adaptively plastic. We present an individual-based heuristic model to compare the adaptive dynamics of populations composed of plastic or non-plastic genotypes under a wide range of scenarios where we modify environmental variation, mutation rate and costs of plasticity. The model shows that adaptive plasticity contributes to the maintenance of genetic variation within populations, reduces bottlenecks when facing rapid environmental changes and confers an overall faster rate of adaptation. In fluctuating environments, plasticity is favoured by selection and maintained in the population. However, if the environment stabilizes and costs of plasticity are high, plasticity is reduced by selection, leading to genetic assimilation, which could result in species diversification. More broadly, our model shows that adaptive plasticity is a common consequence of selection under environmental heterogeneity, and hence a potentially common phenomenon in nature. Thus, taking adaptive plasticity into account substantially extends our view of adaptive evolution.     

Developmental plasticity, morphological variation and evolvability: a multilevel analysis of morphometric integration in the shape of compound leaves

The structure of compound leaves provides flexibility for morphological change by variation in the shapes, sizes and arrangement of leaflets. Here, we conduct a multilevel analysis of shape variation in compound leaves to explore the developmental plasticity and evolutionary potential that are the basis of diversification in leaf shape. We use the methods of geometric morphometrics to study the shapes of individual leaflets and whole leaves in 20 taxa of Potentilla (sensu lato). A newly developed test based on the bootstrap approach suggests that uncertainty in the molecular phylogeny precludes firm conclusions whether there is a phylogenetic signal in the data on leaf shape. For variation among taxa, variation within taxa, as well as fluctuating asymmetry, there is evidence of strong morphological integration. The patterns of variation are similar across all three levels, suggesting that integration within taxa may act as a constraint on evolutionary change.     

Developmental plasticity and the evolution of parental effects

One of the outstanding challenges for evolutionary biologists is to understand how developmental plasticity can influence the evolutionary process. Developmental plasticity frequently involves parental effects, which might enable adaptive and context-dependent transgenerational transmission of phenotypic strategies. However, parent-offspring conflict will frequently result in parental effects that are suboptimal for parents, offspring or both. The fitness consequences of parental effects at evolutionary equilibrium will depend on how conflicts can be resolved by modifications of developmental processes, suggesting that proximate studies of development can inform ultimate questions. Furthermore, recent studies of plants and animals show how studies of parental effects in an ecological context provide important insights into the origin and evolution of adaptation under variable environmental conditions.     

Homeostatic plasticity in the CNS: synaptic and intrinsic forms

The study of experience-dependent plasticity has been dominated by questions of how Hebbian plasticity mechanisms act during learning and development. This is unsurprising as Hebbian plasticity constitutes the most fully developed and influential model of how information is stored in neural circuits and how neural circuitry can develop without extensive genetic instructions. Yet Hebbian plasticity may not be sufficient for understanding either learning or development: the dramatic changes in synapse number and strength that can be produced by this kind of plasticity tend to threaten the stability of neural circuits. Recent work has suggested that, in addition to Hebbian plasticity, homeostatic regulatory mechanisms are active in a variety of preparations. These mechanisms alter both the synaptic connections between neurons and the intrinsic electrical properties of individual neurons, in such a way as to maintain some constancy in neuronal properties despite the changes wrought by Hebbian mechanisms. Here we review the evidence for homeostatic plasticity in the central nervous system, with special emphasis on results from cortical preparations.     

Comparison of morphological and genetic analyses reveals cryptic divergence and morphological plasticity in Stylophora (Cnidaria, Scleractinia)

A combined morphological and genetic study of the coral genus Stylophora investigated species boundaries in the Gulf of Aden, Yemen. Two mitochondrial regions, including the hypervariable IGS9 spacer and the control region, and a fragment of rDNA were used for phylogenetic analysis. Results were compared by multivariate analysis on the basis of branch morphology and corallite morphometry. Two species were clearly discriminated by both approaches. The first species was characterised by small corallites and a low morphological variability and was ascribed to a new geographical record of Stylophora madagascarensis on the basis of its phylogenetic distinction and its morphological similarity to the type material. The second species was characterised by larger corallite size and greater morphological variability and was ascribed to Stylophora pistillata. The analysis was extended to the intrageneric level for other S. pistillata populations from the Red Sea and the Pacific Ocean. Strong internal divergence was evident in the genus Stylophora. S. pistillata populations were split into two highly divergent Red Sea/Gulf of Aden and western Pacific lineages with significant morphological overlap, which suggests they represent two distinct cryptic species. The combined use of morphological and molecular approaches, so far proved to be a powerful tool for the re-delineation of species boundaries in corals, provided novel evidence of cryptic divergence in this group of marine metazoans.     

Dynamics of production of sexual forms in aphids: theoretical and experimental evidence for adaptive "coin-flipping" plasticity

The best strategy for an organism to deal with unpredictable environmental conditions is a stochastic one, but it is not easy to distinguish it from nonadaptive randomness in phenotype production, and its convincing demonstrations are lacking. Here we describe a new method for detection of adaptive stochastic polyphenism and apply it to the following problem. In fall, each female of the bird cherry-oat aphid, Rhopalosiphum padi, faces a decision either to produce sexuals, which mate and lay cold-tolerant eggs, or to continue production of cold-sensitive parthenogenetic females, which potentially yields a higher population growth rate but is risky because a cold winter can kill all of her descendants. Using a simulation model, we show that global investment in sexual reproduction should be proportional to winter severity and that variance in the peak date of production of sexual individuals should depend on climate predictability. Both predictions are validated against standardized trap data on aphid flight accompanied by meteorological data, and the predictions support adaptive phenotypic plasticity.     

The alignment between phenotypic plasticity,the major axis of genetic variation and the response to selection

Phenotypic plasticity is the ability of a genotype to produce more than one phenotype in order to match the environment. Recent theory proposes that the major axis of genetic variation in a phenotypically plastic population can align with the direction of selection. Therefore, theory predicts that plasticity directly aids adaptation by increasing genetic variation in the direction favoured by selection and reflected in plasticity. We evaluated this theory in the freshwater crustacean Daphnia pulex, facing predation risk from two contrasting size-selective predators. We estimated plasticity in several life-history traits, the G matrix of these traits, the selection gradients on reproduction and survival, and the predicted responses to selection. Using these data, we tested whether the genetic lines of least resistance and the predicted response to selection aligned with plasticity. We found predator environment-specific G matrices, but shared genetic architecture across environments resulted in more constraint in the G matrix than in the plasticity of the traits, sometimes preventing alignment of the two. However, as the importance of survival selection increased, the difference between environments in their predicted response to selection increased and resulted in closer alignment between the plasticity and the predicted selection response. Therefore, plasticity may indeed aid adaptation to new environments.     

Selection in a fluctuating environment leads to decreased genetic variation and facilitates the evolution of phenotypic plasticity

Changes in the environment are expected to induce changes in the quantitative genetic variation, which influences the ability of a population to adapt to environmental change. Furthermore, environmental changes are not constant in time, but fluctuate. Here, we investigate the effect of rapid, continuous and/or fluctuating temperature changes in the seed beetle Callosobruchus maculatus, using an evolution experiment followed by a split-brood experiment. In line with expectations, individuals responded in a plastic way and had an overall higher potential to respond to selection after a rapid change in the environment. After selection in an environment with increasing temperature, plasticity remained unchanged (or decreased) and environmental variation decreased, especially when fluctuations were added; these results were unexpected. As expected, the genetic variation decreased after fluctuating selection. Our results suggest that fluctuations in the environment have major impact on the response of a population to environmental change; in a highly variable environment with low predictability, a plastic response might not be beneficial and the response is genetically and environmentally canalized resulting in a low potential to respond to selection and low environmental sensitivity. Interestingly, we found greater variation for phenotypic plasticity after selection, suggesting that the potential for plasticity to evolve is facilitated after exposure to environmental fluctuations. Our study highlights that environmental fluctuations should be considered when investigating the response of a population to environmental change.     

Phylogenetic and population genetic analyses of Phaeosphaeria nodorum and its close relatives indicate cryptic species and an origin in the Fertile Crescent

The origin of the fungal wheat pathogen Phaeosphaeria nodorum remains unclear despite earlier intensive global population genetic and phylogeographical studies. We sequenced 1683 bp distributed across three loci in 355 globally distributed Phaeosphaeria isolates, including 74 collected in Iran near the center of origin of wheat. We identified nine phylogenetically distinct clades, including two previously unknown species tentatively named P1 and P2 collected in Iran. Coalescent analysis indicates that P1 and P2 are sister species of P. nodorum and the other Phaeosphaeria species identified in our analysis. Two species, P. nodorum and P. avenaria f. sp. tritici 1 (Pat1), comprised ～85% of the sampled isolates, making them the dominant wheat-infecting pathogens within the species complex. We designed a PCR-RFLP assay to distinguish P. nodorum from Pat1. Approximately 4% of P. nodorum and Pat1 isolates showed evidence of hybridization. Measures of private allelic richness at SSR and sequence loci suggest that the center of origin of P. nodorum coincides with its host in the Fertile Crescent. We hypothesize that the origin of this species complex is also in the Fertile Crescent, with four species out of nine found exclusively in the Iranian collections.     

Heritable genetic variation via mutation-selection balance: Lerch's zeta meets the abdominal bristle

Most quantitative traits in most populations exhibit heritable genetic variation. Lande proposed that high levels of heritable variation may be maintained by mutation in the face of stabilizing selection. Several analyses have appeared of two distinct models with n additive polygenic loci subject to mutation and stabilizing selection. Each is reviewed and a new analysis and model are presented. Lande and Fleming analyzed extensions of a model originally treated by Kimura which assumes a continuum of possible allelic effects at each locus. Latter and Bulmer analyzed a model with diallelic loci. The published analyses of these models lead to qualitatively different predictions concerning the dependence of the equilibrium genetic variance on the underlying biological parameters. A new asymptotic analysis of the Kimura model shows that the different predictions are not consequences of the number of alleles assumed but rather are attributable to assumptions concerning the relative magnitudes of per locus mutation rates, the phenotypic effects of mutation, and the intensity of selection. This conclusion is reinforced by analysis of a model with triallelic loci. None of the approximate analyses presented are mathematically rigorous. To quantify their accuracy and display the domains of validity for alternative approximations, numerically determined equilibria are presented. In addition, empirical estimates of mutation rates and selection intensity are reviewed, revealing weaknesses in both the data and its connection to the models. Although the mathematical results and underlying biological requirements of my analyses are quite different from those of Lande, the results do not refute his hypothesis that considerable additive genetic variance may be maintained by mutation-selection balance. However, I argue that the validity of this hypothesis can only be determined with additional data and mathematics.     

Genetic variation in time and space: the use of herbarium specimens to reconstruct patterns of genetic variation in the endangered orchid Anacamptis palustris

Habitat alteration, fragmentation and destruction as a consequence of human impact are a global phenomenon. Here we document changes in genetic variation in the marsh orchid Anacamptis palustris as a consequence of such habitat changes. We examined historical specimens that were collected during the nineteenth and early twentieth centuries, prior to the most recent massive habitat changes affecting this species. Sequences of a hypervariable region in the plastid DNA, located in the tRNA^LEU intron, from herbarium vouchers were compared with those from a near-exhaustive survey of the extant A. palustris populations on the Italian peninsula. It was found that private haplotypes and alleles found in small, extant populations were once widespread and more common in historic populations and that alleles, once present in historic populations, have gone extinct. In addition, genetic differentiation among populations has increased over time and haplotype frequencies significantly differ among historic and extant populations. These results document that human induced habitat changes have reduced genetic diversity and increased the importance of random genetic drift in this species. It is concluded that the analysis of herbarium specimens may provide important insights into changes of genetic diversity over time and may be critical for correct inference of the evolutionary history of rare and endangered species.     

Nuclear markers reveal unexpected genetic variation and a Congolese-Nilotic origin of the Lake Victoria cichlid species flock

Phylogenetic analyses based on mitochondrial (mt) DNA have indicated that the cichlid species flock of the Lake Victoria region is derived from a single ancestral species found in East African rivers, closely related to the ancestor of the Lake Malawi cichlid species flock. The Lake Victoria flock contains ten times less mtDNA variation than the Lake Malawi radiation, consistent with current estimates of the ages of the lakes. We present results of a phylogenetic investigation using nuclear (amplified fragment length polymorphism) markers and a wider coverage of riverine haplochromines. We demonstrate that the Lake Victoria-Edward flock is derived from the morphologically and ecologically diverse cichlid genus Thoracochromis from the Congo and Nile, rather than from the phenotypically conservative East African Astatotilapia. This implies that the ability to express much of the morphological diversity found in the species flock may by far pre-date the origin of the flock. Our data indicate that the nuclear diversity of the Lake Victoria-Edward species flock is similar to that of the Lake Malawi flock, indicating that the genetic diversity is considerably older than the 15 000 years that have passed since the lake began to refill. Most of this variation is manifested in trans-species polymorphisms, indicating very recent cladogenesis from a genetically very diverse founder stock. Our data do not confirm strict monophyly of either of the species flocks, but raise the possibility that these flocks have arisen from hybrid swarms.