When the optimal phenotype differs among environments, adaptive phenotypic plasticity can evolve unless constraints impede such evolution. Costs and limits of plasticity have been proposed as ...important constraints on the evolution of plasticity, yet confusion exists over their distinction. We attempt to clarify these concepts by reviewing their categorization and measurement, highlighting how costs and limits are defined in different currencies (and may describe the same phenomenon). Conclusions from studies that measure the costs of plasticity have been equivocal, but we caution that these conclusions may be premature owing to a potentially common correlation between environment-specific trait values and the magnitude of trait plasticities (i.e. multi-collinearity) that results in imprecise and/or biased estimates of the costs. Meanwhile, our understanding of the limits of plasticity, and how they may be underlain by the costs of plasticity, is still in its infancy. Based on our re-evaluation of these constraints, we discuss areas for future research.
The extent of convergent molecular evolution is largely unknown, yet is critical to understanding the genetics of adaptation. Target site insensitivity to cardenolides is a prime candidate for ...studying molecular convergence because herbivores in six orders of insects have specialized on these plant poisons, which gain their toxicity by blocking an essential transmembrane carrier, the sodium pump (Na,K-ATPase). We investigated gene sequences of the Na,K-ATPase α-subunit in 18 insects feeding on cardenolide-containing plants (spanning 15 genera and four orders) to screen for amino acid substitutions that might lower sensitivity to cardenolides. The replacement N122H that was previously shown to confer resistance in the monarch butterfly (Danaus plexippus) and Chrysochus leaf beetles was found in four additional species, Oncopeltus fasciatus and Lygaeus kalmii (Heteroptera, Lygaeidae), Labidomera clivicollis (Coleoptera, Chrysomelidae), and Liriomyza asclepiadis (Diptera, Agromyzidae). Thus, across 300 Myr of insect divergence, specialization on cardenolide-containing plants resulted in molecular convergence for an adaptation likely involved in coevolution. Our screen revealed a number of other substitutions connected to cardenolide binding in mammals. We confirmed that some of the particular substitutions provide resistance to cardenolides by introducing five distinct constructs of the Drosophila melanogaster gene into susceptible eucaryotic cells under an ouabain selection regime. These functional assays demonstrate that combined substitutions of Q ¹¹¹ and N ¹²² are synergistic, with greater than twofold higher resistance than either substitution alone and >12-fold resistance over the wild type. Thus, even across deep phylogenetic branches, evolutionary degrees of freedom seem to be limited by physiological constraints, such that the same molecular substitutions confer adaptation.
The visual word form area (VWFA) is a region of human inferotemporal cortex that emerges at a fixed location in the occipitotemporal cortex during reading acquisition and systematically responds to ...written words in literate individuals. According to the neuronal recycling hypothesis, this region arises through the repurposing, for letter recognition, of a subpart of the ventral visual pathway initially involved in face and object recognition. Furthermore, according to the biased connectivity hypothesis, its reproducible localization is due to preexisting connections from this subregion to areas involved in spoken-language processing. Here, we evaluate those hypotheses in an explicit computational model. We trained a deep convolutional neural network of the ventral visual pathway, first to categorize pictures and then to recognize written words invariantly for case, font, and size. We show that the model can account for many properties of the VWFA, particularly when a subset of units possesses a biased connectivity to word output units. The network develops a sparse, invariant representation of written words, based on a restricted set of reading-selective units. Their activation mimics several properties of the VWFA, and their lesioning causes a reading-specific deficit. The model predicts that, in literate brains, written words are encoded by a compositional neural code with neurons tuned either to individual letters and their ordinal position relative to word start or word ending or to pairs of letters (bigrams).
Plant‐mediated interactions between co‐occurring herbivores play an important role in insect herbivore communities. Although induced resistance pathways associated with jasmonic acid and salicylic ...acid are often implicated in such plant‐mediated interactions, there are few examples from non‐model systems involving specialized herbivores that regularly interact in nature. Here, we tested reciprocal impacts between co‐occurring specialist herbivores from two feeding guilds, monarch caterpillars Danaus plexippus and oleander aphids Aphis nerii, on two co‐occurring and closely related, but defensively contrasting milkweeds, Asclepias syriaca and A. tuberosa. Larvae grew 38% faster on aphid‐infested A. syriaca compared to controls. Reciprocally, aphid growth was >50% lower on caterpillar‐damaged A. syriaca compared to controls. While caterpillar feeding on A. syriaca induced a jasmonate burst and higher defensive end products (cardenolides and latex), this induction was substantially attenuated in the presence of aphids. We found a negative correlation between jasmonic acid and salicylic acid only on A. syriaca infested by both caterpillars an aphids. Asclepias tuberosa displayed distinct hormonal dynamics and lacked induction of defensive end products. Accordingly, we found no evidence for plant‐mediated interactions between monarchs and aphids on A. tuberosa. Thus, A. syriaca has specific responses to each herbivore, but if challenged simultaneously, the outcome is asymmetric: monarchs benefit from defence attenuation by aphids, while aphids are impaired by monarch feeding. Our results suggest phytohormonal trade‐offs induced by two feeding guilds can differ between closely related plant species, and our notion of trade‐offs in defence based on phytohormonal pathways would improve with further comparative designs from both model and non‐model systems.
Typically, computational screens for new materials sharply constrain the compositional search space, structural search space, or both, for the sake of tractability. To lift these constraints, we ...construct a machine learning model from a database of thousands of density functional theory (DFT) calculations. The resulting model can predict the thermodynamic stability of arbitrary compositions without any other input and with six orders of magnitude less computer time than DFT. We use this model to scan roughly 1.6 million candidate compositions for novel ternary compounds (A sub(x)B sub(y)C sub(z)), and predict 4500 new stable materials. Our method can be readily applied to other descriptors of interest to accelerate domain-specific materials discovery.
Both an individual's genotype and environment govern its phenotype, and this phenotype may have extended consequences for species interactions and communities. We examined the importance of plant ...genotype and environmental factors operating at large (habitat) and small (microhabitat) spatial scales in affecting a multitrophic arthropod community on plants. We planted 926 plants from 14 genotypes of Oenothera biennis into five natural habitats that represent the range of environments in which this plant locally occurs. Genotypic differences among plants accounted for as much as 41% of the variation in arthropod diversity (Simpson's diversity index) and also affected arthropod evenness, richness, abundance, and biomass on individual plants. However, the effects of particular plant genotypes on the arthropod community varied across habitats (i.e., there were significant plant genotype-by-habitat interactions). Plant genotype explained more variation in the arthropod community than did environmental variation among microhabitats, but less variation than habitats, as predicted by the scale-dependent hypothesis. Herbivores and omnivores were more strongly affected by plant genetic variation than predators, consistent with the notion that phytophagous insects undergo stronger reciprocal interactions with plants than do predators. We detected heritable variation in arthropod community variables and the ability for the herbivore community to select on plant traits, suggesting that evolution in O. biennis can lead to changes in the arthropod community. Genetic variation in plant size, architecture, and reproductive phenology were the plant traits most strongly correlated with arthropod community variables. Our results demonstrate that genotype-by-environment interactions are a major determinant of arthropod community structure.
Cardenolides are remarkable steroidal toxins that have become model systems, critical in the development of theories for chemical ecology and coevolution. Because cardenolides inhibit the ubiquitous ...and essential animal enzyme Na+/K+-ATPase, most insects that feed on cardenolidecontaining plants are highly specialized. With a huge diversity of chemical forms, these secondary metabolites are sporadically distributed across 12 botanical families, but dominate the Apocynaceae where they are found in > 30 genera. Studies over the past decade have demonstrated patterns in the distribution of cardenolides among plant organs, including all tissue types, and across broad geographic gradients within and across species. Cardenolide production has a genetic basis and is subject to natural selection by herbivores. In addition, there is strong evidence for phenotypic plasticity, with the biotic and abiotic environment predictably impacting cardenolide production. Mounting evidence indicates a high degree of specificity in herbivore-induced cardenolides in Asclepias. While herbivores of cardenolide-containing plants often sequester the toxins, are aposematic, and possess several physiological adaptations (including target site insensitivity), there is strong evidence that these specialists are nonetheless negatively impacted by cardenolides. While reviewing both the mechanisms and evolutionary ecology of cardenolide-mediated interactions, we advance novel hypotheses and suggest directions for future work.
Genomic analyses of cancer have identified recurrent point mutations in the RNA splicing factor-encoding genes SF3B1, U2AF1, and SRSF2 that confer an alteration of function. Cancer cells bearing ...these mutations are preferentially dependent on wild-type (WT) spliceosome function, but clinically relevant means to therapeutically target the spliceosome do not currently exist. Here we describe an orally available modulator of the SF3b complex, H3B-8800, which potently and preferentially kills spliceosome-mutant epithelial and hematologic tumor cells. These killing effects of H3B-8800 are due to its direct interaction with the SF3b complex, as evidenced by loss of H3B-8800 activity in drug-resistant cells bearing mutations in genes encoding SF3b components. Although H3B-8800 modulates WT and mutant spliceosome activity, the preferential killing of spliceosome-mutant cells is due to retention of short, GC-rich introns, which are enriched for genes encoding spliceosome components. These data demonstrate the therapeutic potential of splicing modulation in spliceosome-mutant cancers.
Threats to several of the world’s great animal migrations necessitate a research agenda focused on identifying drivers of their population dynamics. The monarch butterfly is an iconic species whose ...continental migratory population in eastern North America has been declining precipitously. Recent analyses have linked the monarch decline to reduced abundance of milkweed host plants in the USA caused by increased use of genetically modified herbicide-resistant crops. To identify the most sensitive stages in the monarch’s annual multi-generational migration, and to test the milkweed limitation hypothesis, we analyzed 22 years of citizen science records from four monitoring programs across North America. We analyzed the relationships between butterfly population indices at successive stages of the annual migratory cycle to assess demographic connections and to address the roles of migrant population size versus temporal trends that reflect changes in habitat or resource quality. We find a sharp annual population decline in the first breeding generation in the southern USA, driven by the progressively smaller numbers of spring migrants from the overwintering grounds in Mexico. Monarch populations then build regionally during the summer generations. Contrary to the milkweed limitation hypothesis, we did not find statistically significant temporal trends in stage-to-stage population relationships in the mid-western or northeastern USA. In contrast, there are statistically significant negative temporal trends at the overwintering grounds in Mexico, suggesting that monarch success during the fall migration and re-establishment strongly contributes to the butterfly decline. Lack of milkweed, the only host plant for monarch butterfly caterpillars, is unlikely to be driving the monarch’s population decline. Conservation efforts therefore require additional focus on the later phases in the monarch’s annual migratory cycle. We hypothesize that lack of nectar sources, habitat fragmentation, continued degradation at the overwintering sites, or other threats to successful fall migration are critical limiting factors for declining monarchs.
The μeV axion is a well-motivated extension to the standard model. The Axion Dark Matter eXperiment (ADMX) collaboration seeks to discover this particle by looking for the resonant conversion of ...dark-matter axions to microwave photons in a strong magnetic field. In this Letter, we report results from a pathfinder experiment, the ADMX "Sidecar," which is designed to pave the way for future, higher mass, searches. This testbed experiment lives inside of and operates in tandem with the main ADMX experiment. The Sidecar experiment excludes masses in three widely spaced frequency ranges (4202-4249, 5086-5799, and 7173-7203 MHz). In addition, Sidecar demonstrates the successful use of a piezoelectric actuator for cavity tuning. Finally, this publication is the first to report data measured using both the TM_{010} and TM_{020} modes.
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