Evolution and diversity of axon guidance Robo receptor family genes

The diversity of axon guidance (AG) receptors reflects gains in complexity of the animal nervous system during evolution. Members of the Roundabout (Robo) family of receptors interact with Slit proteins and play important roles in many developmental processes, including AG and neural crest cell migration. There are four members of the Robo gene family. However, the evolutionary history of Robo family genes remain obscure. We analyzed the distribution of Robo family members in metazoan species ranging in complexity from hydras to humans. We undertook a phylogenetic analysis in metazoans, synteny analysis, and ancestral chromosome mapping in vertebrates, and detected selection pressure and functional divergence among four mammalian Robo paralogs. Based on our analysis, we proposed that the ancestral Robo gene could have undergone a tandem duplication in the vertebrate ancestor; then one round of whole genome duplication events occurred before the divergence of ancestral lamprey and gnathostome, generating four paralogs in early vertebrates. Robo4 paralog underwent segmental loss in the following evolutionary process. Our results showed that Robo3 paralog is under more powerful purifying selection pressure compared with other three paralogs, which could correlate with its unique expression pattern and function. Furthermore, we found four sites under positive selection pressure on the Ig1‐2 domains of Robo4 that might interfere with its binding to Slits ligand. Diverge analysis at the amino acid level showed that Robo4 paralog have relatively greater functional diversifications than other Robo paralogs. This coincides with the fact that Robo4 predominantly functions in vascular endothelial cells but not the nervous system.     

A comprehensive landscape genomics approach for seed sourcing strategies in landscapes under varying degrees of habitat disturbance

As most ecosystems around the world are threatened by anthropogenic degradation and climate change, there is an increasing urgency to implement restoration strategies aiming at ensuring ecosystem self‐sustainability and resilience. An initial step towards that goal relies on selecting the most suitable seed sources for a successful revegetation, which can be extremely challenging in highly degraded landscapes. The most common seed sourcing strategy is to select local seeds because it is assumed that plants experience strong adaptations to their natal sites. An alternative strategy is the selection of climate‐adapted genotypes to future conditions. While considering future climatic projections is important to account for spatial shifts in climate to inform assisted gene flow and translocations, to restore highly degraded landscapes we need a comprehensive approach that first accounts for species adaptations to current at‐site environmental conditions. In this issue of Molecular Ecology Resources, Carvalho et al. present a novel landscape genomics framework to identify the most appropriate seed sourcing strategy for moderately and highly degraded sites by integrating genotype, phenotype and environmental data in a spatially explicit context for two native plant species with potential to help restore iron‐rich Amazonian savannas. This framework is amenable to be applicable and adapted to a broad range of restoration initiatives, as the dichotomy between focusing on the current or future climatic conditions should depend on the goals and environmental circumstances of each restoration site.     

Testing the effect of restoration‐focused silviculture on oak regeneration and groundlayer plant communities in urban–exurban oak woodlands

Throughout their global range, oak‐dominated ecosystems have undergone state changes in stand structure and composition. Land managers face an especially acute challenge in restoring oak ecosystems and promoting oak regeneration in urban–exurban areas, where high‐intensity silvicultural treatments are often not feasible. To investigate low‐intensity management alternatives which could be widely applied in urban–exurban forests, a large‐scale adaptive management experiment was implemented in Lake County, IL, in 2012. Five canopy manipulation treatments of varying intensity, timing, and spatial aggregation were replicated across three study areas and oak seedlings were under‐planted into treatment units following management. Responses of understory light environment, shrub and groundlayer plant communities, and survival and growth of underplanted oak seedlings were evaluated. Understory light availability, canopy openness, total groundlayer plant cover, and groundlayer species diversity all differed among treatments. However, although understory light availability was significantly increased by canopy manipulation, groundlayer communities and oak seedling survival and growth did not differ among treatments. High overall seedling survival rates suggest current conditions are amenable to oak regeneration, but long‐term monitoring will be needed to assess the potential for seedlings to transition to the sapling and canopy layers. Early results demonstrate that canopy‐focused silvicultural treatments can affect the understory light environment and, to some degree, groundlayer plant communities. However, underplanting of oak seedlings paired with subcanopy thinning may be sufficient to restore an oak seedling layer, and (when necessary or preferred) canopy manipulation could potentially be deferred until later in the restoration timeline to promote oak recruitment.     

Science,Uncertainty, and Values in Ecological Restoration: A Case Study in Structured Decision‐Making and Adaptive Management

This article demonstrates a structured and collaborative approach to decision‐making in the context of adaptive management experiments, using a case study involving the restoration of a hydrological regime in a regulated river in western Canada. It provides a framework based on principles of decision analysis for structuring difficult multi‐attribute decisions and building the trust and technical capacity needed to implement them. Participants included ecologists and fisheries biologists, government regulators, electric utility employees, and representatives of aboriginal communities. The case study demonstrates a values‐based approach to implementing adaptive management that addresses some of the long‐standing difficulties associated with integrating adaptive management into restoration decisions. It highlights practical methods for incorporating participants' values concerned with learning, cultural quality, and stewardship as part of developing a decision‐making and monitoring framework for restoration initiatives. It also provides an example of how to implement principles of meaningful consultation in a restoration context, with emphasis on ensuring that all voices and concerns are heard and meaningfully incorporated. Participants have adopted the framework as a model to guide future collaborative decision‐making processes involving Aboriginal communities, regulatory agencies, and other parties.     

Do habitat shifts drive diversification in teleost fishes? An example from the pufferfishes (Tetraodontidae)

Habitat shifts are implicated as the cause of many vertebrate radiations, yet relatively few empirical studies quantify patterns of diversification following colonization of new habitats in fishes. The pufferfishes (family Tetraodon‐tidae) occur in several habitats, including coral reefs and freshwater, which are thought to provide ecological opportunity for adaptive radiation, and thus provide a unique system for testing the hypothesis that shifts to new habitats alter diversification rates. To test this hypothesis, we sequenced eight genes for 96 species of pufferfishes and closely related porcupine fishes, and added 19 species from sequences available in GenBank. We time‐calibrated the molecular phylogeny using three fossils, and performed several comparative analyses to test whether colonization of novel habitats led to shifts in the rate of speciation and body size evolution, central predictions of clades experiencing ecological adaptive radiation. Colonization of freshwater is associated with lower rates of cladogenesis in pufferfishes, although these lineages also exhibit accelerated rates of body size evolution. Increased rates of cladogenesis are associated with transitions to coral reefs, but reef lineages surprisingly exhibit significantly lower rates of body size evolution. These results suggest that ecological opportunity afforded by novel habitats may be limited for pufferfishes due to competition with other species, constraints relating to pufferfish life history and trophic ecology, and other factors.     

Quantifying the effects of migration and mutation on adaptation and demography in spatially heterogeneous environments

How do mutation and gene flow influence population persistence, niche expansion and local adaptation in spatially heterogeneous environments? In this article, we analyse a demographic and evolutionary model of adaptation to an environment containing two habitats in equal frequencies, and we bridge the gap between different theoretical frameworks. Qualitatively, our model yields four qualitative types of outcomes: (i) global extinction of the population, (ii) adaptation to one habitat only, but also adaptation to both habitats with, (iii) specialized phenotypes or (iv) with generalized phenotypes, and we determine the conditions under which each equilibrium is reached. We derive new analytical approximations for the local densities and the distributions of traits in each habitat under a migration–selection–mutation balance, compute the equilibrium values of the means, variances and asymmetries of the local distributions of phenotypes, and contrast the effects of migration and mutation on the evolutionary outcome. We then check our analytical results by solving our model numerically, and also assess their robustness in the presence of demographic stochasticity. Although increased migration results in a decrease in local adaptation, mutation in our model does not influence the values of the local mean traits. Yet, both migration and mutation can have dramatic effects on population size and even lead to metapopulation extinction when selection is strong. Niche expansion, the ability for the population to adapt to both habitats, can also be prevented by small migration rates and a reduced evolutionary potential characterized by rare mutation events of small effects; however, niche expansion is otherwise the most likely outcome. Although our results are derived under the assumption of clonal reproduction, we finally show and discuss the links between our model and previous quantitative genetics models.     

Anisotropic adaptive finite element method for modelling blood flow

In this study, we present an adaptive anisotropic finite element method (FEM) and demonstrate how computational efficiency can be increased when applying the method to the simulation of blood flow in the cardiovascular system. We use the SUPG formulation for the transient 3D incompressible Navier–Stokes equations which are discretised by linear finite elements for both the pressure and the velocity field.

Given the pulsatile nature of the flow in blood vessels we have pursued adaptivity based on the average flow over a cardiac cycle. Error indicators are derived to define an anisotropic mesh metric field. Mesh modification algorithms are used to anisotropically adapt the mesh according to the desired size field. We demonstrate the efficiency of the method by first applying it to pulsatile flow in a straight cylindrical vessel and then to a porcine aorta with a stenosis bypassed by a graft. We demonstrate that the use of an anisotropic adaptive FEM can result in an order of magnitude reduction in computing time with no loss of accuracy compared to analyses obtained with uniform meshes.     

Stress-Induced Mutagenesis in Bacteria

ABSTRACT

Bacteria spend their lives buffeted by changing environmental conditions. To adapt to and survive these stresses, bacteria have global response systems that result in sweeping changes in gene expression and cellular metabolism. These responses are controlled by master regulators, which include: alternative sigma factors, such as RpoS and RpoH; small molecule effectors, such as ppGpp; gene repressors such as LexA; and, inorganic molecules, such as polyphosphate. The response pathways extensively overlap and are induced to various extents by the same environmental stresses. These stresses include nutritional deprivation, DNA damage, temperature shift, and exposure to antibiotics. All of these global stress responses include functions that can increase genetic variability. In particular, up-regulation and activation of error-prone DNA polymerases, down-regulation of error-correcting enzymes, and movement of mobile genetic elements are common features of several stress responses. The result is that under a variety of stressful conditions, bacteria are induced for genetic change. This transient mutator state may be important for adaptive evolution.     

Hierarchies of evolutionary radiation in the world’s most species rich vertebrate group,the Neotropical Pristimantis leaf litter frogs

The Neotropical leaf litter frog genus Pristimantis is very species-rich, with 526 species described to date, but the full extent of its diversity is much higher and remains unknown. This study explores the phylogenetic processes and resulting evolutionary patterns of diversification in Pristimantis. Given the well-recognised failure of morphology- and community-based species groups to describe diversity within the genus, we apply a new test for the presence and phylogenetic distribution of higher evolutionary units. We developed a phylogeny based on 260 individuals encompassing 149 Pristimantis presumed species, sampled at mitochondrial and nuclear genes (3718 base pair alignment), combining new and available sequence data. Our phylogeny broadly agrees with previous studies, both in topology and age estimates, with the origin of Pristimantis at 28.97 (95% HDP =21.59 – 37.33) million years ago (MYA). New taxa that we add to the genus, which had not previously been included in Pristimantis phylogenies, suggest considerable diversity remains to be described. We assessed patterns of lineage origin and recovered 14 most likely (95% CI: 13–19) phylogenetic clusters or higher evolutionary significant units (hESUs) within Pristimantis. Diversification rates decrease towards the present following a density-dependent pattern for Pristimantis overall and for most hESU clusters, reflecting historical evolutionary radiation. The timing of diversification suggests that geological events in the Miocene, such as Andes orogenesis and Pebas system formation and drainage, may have had a direct or indirect impact on the evolution of Pristimantis and thus contributed to the origins of evolutionary independent phylogenetic clusters.     

Proteomics advances for precision therapy in ovarian cancer

ABSTRACT

Introduction: Due to the relatively low mutation rate and high frequency of copy number variation, finding actionable genetic drivers of high-grade serous carcinoma (HGSC) is a challenging task. Furthermore, emerging studies show that genetic alterations are frequently poorly represented at the protein level adding a layer of complexity. With improvements in large-scale proteomic technologies, proteomics studies have the potential to provide robust analysis of the pathways driving high HGSC behavior.

Areas covered: This review summarizes recent large-scale proteomics findings across adequately sized ovarian cancer sample sets. Key words combined with ‘ovarian cancer’ including ‘proteomics’, ‘proteogenomic’, ‘reverse-phase protein array’, ‘mass spectrometry’, and ‘adaptive response’, were used to search PubMed.

Expert opinion: Proteomics analysis of HGSC as well as their adaptive responses to therapy can uncover new therapeutic liabilities, which can reduce the emergence of drug resistance and potentially improve patient outcomes. There is a pressing need to better understand how the genomic and epigenomic heterogeneity intrinsic to ovarian cancer is reflected at the protein level and how this information could be used to improve patient outcomes.