Supergenes on Steroids

At the birth of supergenes, the genomic landscape is dramatically re-organized leading to pronounced differences in phenotypes and increased intrasexual diversity. Two of the best-studied supergenes in vertebrates are arguably the inversion polymorphisms on chromosomes 2 and 11 in the white-throated sparrow (Zonotrichia albicollis) and the ruff (Calidris pugnax), respectively. In both species, regions of suppressed recombination determine plumage coloration and social behavioral phenotypes. Despite the apparent lack of gene overlap between these two supergenes, in both cases the alternative phenotypes seem to be driven largely by alterations in steroid hormone pathways. Here, we explore the interplay between genomic architecture and steroid-related genes. Due to the highly pleiotropic effects of such genes and their universal involvement in social behavior and genomic architecture, forces favouring their linkage are likely to have substantial effects on the evolution of behavioral phenotypes, individual fitness, and life history strategies. We propose that the differentiation of steroid-related genes, inside both supergenes, lies at the core of phenotypic differentiation in both of these interesting species.

Differential Proteomic Analysis of Astrocytes and Astrocytes-Derived Extracellular Vesicles from Control and Rai Knockout Mice: Insights into the Mechanisms of Neuroprotection

Reactive astrocytes are a hallmark of neurodegenerative disease including multiple sclerosis. It is widely accepted that astrocytes may adopt alternative phenotypes depending on a combination of environmental cues and intrinsic features in a highly plastic and heterogeneous manner. However, we still lack a full understanding of signals and associated signaling pathways driving astrocyte reaction and of the mechanisms by which they drive disease. We have previously shown in the experimental autoimmune encephalomyelitis mouse model that deficiency of the molecular adaptor Rai reduces disease severity and demyelination. Moreover, using primary mouse astrocytes, we showed that Rai contributes to the generation of a pro-inflammatory central nervous system (CNS) microenvironment through the production of nitric oxide and IL-6 and by impairing CD39 activity in response to soluble factors released by encephalitogenic T cells. Here, we investigated the impact of Rai expression on astrocyte function both under basal conditions and in response to IL-17 treatment using a proteomic approach. We found that astrocytes and astrocyte-derived extracellular vesicles contain a set of proteins, to which Rai contributes, that are involved in the regulation of oligodendrocyte differentiation and myelination, nitrogen metabolism, and oxidative stress. The HIF-1α pathway and cellular energetic metabolism were the most statistically relevant molecular pathways and were related to ENOA and HSP70 dysregulation.

Contribution of Epigenetic Mechanisms in the Regulation of Environmentally-Induced Polyphenism in Insects

Many insect species display a remarkable ability to produce discrete phenotypes in response to changes in environmental conditions. Such phenotypic plasticity is referred to as polyphenism. Seasonal, dispersal and caste polyphenisms correspond to the most-studied examples that are environmentally-induced in insects. Cues that induce such dramatic phenotypic changes are very diverse, ranging from seasonal cues, habitat quality changes or differential larval nutrition. Once these signals are perceived, they are transduced by the neuroendocrine system towards their target tissues where gene expression reprogramming underlying phenotypic changes occur. Epigenetic mechanisms are key regulators that allow for genome expression plasticity associated with such developmental switches. These mechanisms include DNA methylation, chromatin remodelling and histone post-transcriptional modifications (PTMs) as well as non-coding RNAs and have been studied to various extents in insect polyphenism. Differential patterns of DNA methylation between phenotypes are usually correlated with changes in gene expression and alternative splicing events, especially in the cases of dispersal and caste polyphenism. Combinatorial patterns of histone PTMs provide phenotype-specific epigenomic landscape associated with the expression of specific transcriptional programs, as revealed during caste determination in honeybees and ants. Alternative phenotypes are also usually associated with specific non-coding RNA profiles. This review will provide a summary of the current knowledge of the epigenetic changes associated with polyphenism in insects and highlights the potential for these mechanisms to be key regulators of developmental transitions triggered by environmental cues.

Comparative analysis of phenotypic plasticity sheds light on the evolution and molecular underpinnings of locust phase polyphenism

Locusts exhibit one of nature’s most spectacular examples of complex phenotypic plasticity, in which changes in density cause solitary and cryptic individuals to transform into gregarious and conspicuous locusts forming large migrating swarms. We investigated how these coordinated alternative phenotypes might have evolved by studying the Central American locust and three closely related non-swarming grasshoppers in a comparative framework. By experimentally isolating and crowding during nymphal development, we induced density-dependent phenotypic plasticity and quantified the resulting behavioural, morphological, and molecular reaction norms. All four species exhibited clear plasticity, but the individual reaction norms varied among species and showed different magnitudes. Transcriptomic responses were species-specific, but density-responsive genes were functionally similar across species. There were modules of co-expressed genes that were highly correlated with plastic reaction norms, revealing a potential molecular basis of density-dependent phenotypic plasticity. These findings collectively highlight the importance of studying multiple reaction norms from a comparative perspective.

Epigenetic Variability Among Saffron Crocus (Crocus sativus L.) Accessions Characterized by Different Phenotypes

This work represents the first epigenomic study carried out on saffron crocus. Five accessions of saffron, showing differences in tepal pigmentation, yield of saffron and flowering time, were analyzed at the epigenetic level by applying a methylation-sensitive restriction enzyme-sequencing (MRE-seq) approach. Five accession-specific hypomethylomes plus a reference hypomethylome, generated by combining the sequence data from the single accessions, were obtained. Assembled sequences were annotated against existing online databases. In the absence of the Crocus genome, the rice genome was mainly used as the reference as it is the best annotated genome among monocot plants. Comparison of the hypomethylomes revealed many differentially methylated regions, confirming the high epigenetic variability present among saffron accessions, including sequences encoding for proteins that could be good candidates to explain the accessions’ alternative phenotypes. In particular, transcription factors involved in flowering process (MADS-box and TFL) and for the production of pigments (MYB) were detected. Finally, by comparing the generated sequences of the different accessions, a high number of SNPs, likely having arisen as a consequence of the prolonged vegetative propagation, were detected, demonstrating surprisingly high genetic variability. Gene ontology (GO) was performed to map and visualize sequence polymorphisms located within the GOs and to compare their distributions among different accessions. As well as suggesting the possible existence of alternative phenotypes with a genetic basis, a clear difference in polymorphic GO is present among accessions based on their geographic origin, supporting a possible signature of selection in the Indian accession with respect to the Spanish ones.

The Plasticity and Developmental Potential of Termites

Phenotypic plasticity provides organisms with the potential to adapt to their environment and can drive evolutionary innovations. Developmental plasticity is environmentally induced variation in phenotypes during development that arise from a shared genomic background. Social insects are useful models for studying the mechanisms of developmental plasticity, due to the phenotypic diversity they display in the form of castes. However, the literature has been biased toward the study of developmental plasticity in the holometabolous social insects (i.e., bees, wasps, and ants); the hemimetabolous social insects (i.e., the termites) have received less attention. Here, we review the phenotypic complexity and diversity of termites as models for studying developmental plasticity. We argue that the current terminology used to define plastic phenotypes in social insects does not capture the diversity and complexity of these hemimetabolous social insects. We suggest that terminology used to describe levels of cellular potency could be helpful in describing the many levels of phenotypic plasticity in termites. Accordingly, we propose a conceptual framework for categorizing the changes in potential of individuals to express alternative phenotypes through the developmental life stages of termites. We compile from the literature an exemplar dataset on the phenotypic potencies expressed within and between species across the phylogeny of the termites and use this to illustrate how the potencies of different life stages of different species can be described using this framework. We highlight how this conceptual framework can help exploit the rich phenotypic diversity of termites to address fundamental questions about the evolution and mechanisms of developmental plasticity. This conceptual contribution is likely to have wider relevance to the study of other hemimetabolous insects, such as aphids and gall-forming thrips, and may even prove useful for some holometabolous social insects which have high caste polyphenism.

Extreme developmental instability associated with wing plasticity in pea aphids

A key focus of evolutionary developmental biology is on how phenotypic diversity is generated. In particular, both plasticity and developmental instability contribute to phenotypic variation among genetically identical individuals, but the interactions between the two phenomena and their general fitness impacts are unclear. We discovered a striking example of asymmetry in pea aphids: the presence of wings on one side and the complete or partial absence of wings on the opposite side. We used this asymmetric phenotype to study the connection between plasticity, developmental instability and fitness. We found that this asymmetric wing development (i) occurred equally on both sides and thus is a developmental instability; (ii) is present in some genetically unique lines but not others, and thus has a genetic basis; and (iii) has intermediate levels of fecundity, and thus does not necessarily have negative fitness consequences. We conclude that this dramatic asymmetry may arise from incomplete switching between developmental targets, linking plasticity and developmental instability. We suspect that what we have observed may be a more widespread phenomenon, occurring across species that routinely produce distinct, alternative phenotypes.

Examination of the Effect of Rare Variants in TREM2, ABI3, and PLCG2 in LOAD Through Multiple Phenotypes

Background: Rare variants in PLCG2 (p.P522R), ABI3 (p.S209F), and TREM2 (p.R47H, p.R62H) have been associated with late onset Alzheimer’s disease (LOAD) risk in Caucasians. After the initial report, several studies have found positive results in cohorts of different ethnic background and with different phenotype. Objective: In this study, we aim to evaluate the association of rare coding variants in PLCG2, ABI3, and TREM2 with LOAD risk and their effect at different time points of the disease. Methods: We used a European American cohort to assess the association of the variants prior onset (using CSF Aβ42, tau, and pTau levels, and amyloid imaging as endophenotypes) and after onset (measured as rate of memory decline). Results: We confirm the association with LOAD risk of TREM2 p.R47H, p.R62H and ABI3 p.S209F variants, and the protective effect of PLCG2 p.P522R. In addition, ABI3 and TREM2 gene-sets showed significant association with LOAD risk. TREM2 p.R47H and PLCG2 p.P522R variants were also statistically associated with increase of amyloid imaging and AD progression, respectively. We did not observe any association of ABI3 p.S209F with any of the other AD endophenotypes. Conclusion: The results of this study highlight the importance of including biomarkers and alternative phenotypes to better understand the role of novel candidate genes with the disease.