Combining niche-shift and population genetic analyses predicts rapid phenotypic evolution during invasion

Rapid evolution of non-native species can facilitate invasion success, but recent reviews indicate that such microevolution rarely yields expansion of the climatic niche in the introduced habitats. However, because some invasions originate from a geographically restricted portion of the native species range and its climatic niche, it is possible that the frequency, direction and magnitude of phenotypic evolution during invasion has been underestimated. We explored the utility of niche-shift analyses in the red seaweed Gracilaria vermiculophylla, which expanded its range from the northeastern coastline of Japan to North America, Europe and northwestern Africa within the last 100 years. A genetically-informed climatic niche shift analysis indicates that native source populations occur in colder and highly seasonal habitats, while most non-native populations typically occur in warmer, less seasonal habitats. This climatic niche expansion predicts that non-native populations evolved greater tolerance for elevated heat conditions relative to native source populations. We assayed 935 field-collected and 325 common-garden thalli from 40 locations and as predicted, non-native populations had greater tolerance for ecologically-relevant extreme heat (40°C) than did Japanese source populations. Non-native populations also had greater tolerance for cold and low-salinity stresses relative to source populations. The importance of local adaptation to warm temperatures during invasion was reinforced by evolution of parallel clines: populations from warmer, lower-latitude estuaries had greater heat tolerance than did populations from colder, higher-latitude estuaries in both Japan and eastern North America. We conclude that rapid evolution plays an important role in facilitating the invasion success of this and perhaps other non-native marine species. Genetically-informed ecological niche analyses readily generate clear predictions of phenotypic shifts during invasions, and may help to resolve debate over the frequency of niche conservatism versus rapid adaptation during invasion

Constraints on the evolution of phenotypic plasticity: limits and costs of phenotype and plasticity

Phenotypic plasticity is ubiquitous and generally regarded as a key mechanism for enabling organisms to survive in the face of environmental change. Because no organism is infinitely or ideally plastic, theory suggests that there must be limits (for example, the lack of ability to produce an optimal trait) to the evolution of phenotypic plasticity, or that plasticity may have inherent significant costs. Yet numerous experimental studies have not detected widespread costs. Explicitly differentiating plasticity costs from phenotype costs, we re-evaluate fundamental questions of the limits to the evolution of plasticity and of generalists vs specialists. We advocate for the view that relaxed selection and variable selection intensities are likely more important constraints to the evolution of plasticity than the costs of plasticity. Some forms of plasticity, such as learning, may be inherently costly. In addition, we examine opportunities to offset costs of phenotypes through ontogeny, amelioration of phenotypic costs across environments, and the condition-dependent hypothesis. We propose avenues of further inquiry in the limits of plasticity using new and classic methods of ecological parameterization, phylogenetics and omics in the context of answering questions on the constraints of plasticity. Given plasticity's key role in coping with environmental change, approaches spanning the spectrum from applied to basic will greatly enrich our understanding of the evolution of plasticity and resolve our understanding of limits

New targets for therapy in breast cancer: Small molecule tyrosine kinase inhibitors

Over the past several years many advances have been made in our understanding of critical pathways involved in carcinogenesis and tumor growth. These advances have led to the investigation of small molecule inhibitors of the ErbB family of receptor tyrosine kinases across a broad spectrum of malignancies. In this article we summarize the rationale for targeting members of the ErbB family in breast cancer, and review the preclinical and clinical data for the agents that are furthest in development. In addition, we highlight directions for future research, such as exploration of the potential crosstalk between the ErbB and hormone receptor signal transduction pathways, identification of predictive markers for tumor sensitivity, and development of rational combination regimens that include the tyrosine kinase inhibitors

An Integrated Bioinformatics Approach Identifies Elevated Cyclin E2 Expression and E2F Activity as Distinct Features of Tamoxifen Resistant Breast Tumors

Approximately half of estrogen receptor (ER) positive breast tumors will fail to respond to endocrine therapy. Here we used an integrative bioinformatics approach to analyze three gene expression profiling data sets from breast tumors in an attempt to uncover underlying mechanisms contributing to the development of resistance and potential therapeutic strategies to counteract these mechanisms. Genes that are differentially expressed in tamoxifen resistant vs. sensitive breast tumors were identified from three different publically available microarray datasets. These differentially expressed (DE) genes were analyzed using gene function and gene set enrichment and examined in intrinsic subtypes of breast tumors. The Connectivity Map analysis was utilized to link gene expression profiles of tamoxifen resistant tumors to small molecules and validation studies were carried out in a tamoxifen resistant cell line. Despite little overlap in genes that are differentially expressed in tamoxifen resistant vs. sensitive tumors, a high degree of functional similarity was observed among the three datasets. Tamoxifen resistant tumors displayed enriched expression of genes related to cell cycle and proliferation, as well as elevated activity of E2F transcription factors, and were highly correlated with a Luminal intrinsic subtype. A number of small molecules, including phenothiazines, were found that induced a gene signature in breast cancer cell lines opposite to that found in tamoxifen resistant vs. sensitive tumors and the ability of phenothiazines to down-regulate cyclin E2 and inhibit proliferation of tamoxifen resistant breast cancer cells was validated. Our findings demonstrate that an integrated bioinformatics approach to analyze gene expression profiles from multiple breast tumor datasets can identify important biological pathways and potentially novel therapeutic options for tamoxifen-resistant breast cancers

Early Developmental Responses to Seedling Environment Modulate Later Plasticity to Light Spectral Quality

Correlations between developmentally plastic traits may constrain the joint evolution of traits. In plants, both seedling de-etiolation and shade avoidance elongation responses to crowding and foliage shade are mediated by partially overlapping developmental pathways, suggesting the possibility of pleiotropic constraints. To test for such constraints, we exposed inbred lines of Impatiens capensis to factorial combinations of leaf litter (which affects de-etiolation) and simulated foliage shade (which affects phytochrome-mediated shade avoidance). Increased elongation of hypocotyls caused by leaf litter phenotypically enhanced subsequent elongation of the first internode in response to low red∶far red (R∶FR). Trait expression was correlated across litter and shade conditions, suggesting that phenotypic effects of early plasticity on later plasticity may affect variation in elongation traits available to selection in different light environments

The spatial scale of density-dependent growth and implications for dispersal from nests in juvenile Atlantic salmon

By dispersing from localized aggregations of recruits, individuals may obtain energetic benefits due to reduced experienced density. However, this will depend on the spatial scale over which individuals compete. Here, we quantify this scale for juvenile Atlantic salmon (Salmo salar) following emergence and dispersal from nests. A single nest was placed in each of ten replicate streams during winter, and information on the individual positions (±1 m) and the body sizes of the resulting young-of-the-year (YOY) juveniles was obtained by sampling during the summer. In six of the ten streams, model comparisons suggested that individual body size was most closely related to the density within a mean distance of 11 m (range 2–26 m). A link between body size and density on such a restricted spatial scale suggests that dispersal from nests confers energetic benefits that can counterbalance any survival costs. For the four remaining streams, which had a high abundance of trout and older salmon cohorts, no single spatial scale could best describe the relation between YOY density and body size. Energetic benefits of dispersal associated with reduced local density therefore appear to depend on the abundance of competing cohorts or species, which have spatial distributions that are less predictable in terms of distance from nests. Thus, given a trade-off between costs and benefits associated with dispersal, and variation in benefits among environments, we predict an evolving and/or phenotypically plastic growth rate threshold which determines when an individual decides to disperse from areas of high local density

The case for the continued use of the genus name Mimulus for all monkeyflowers

The genus Mimulus is a well-studied group of plant species, which has for decades allowed researchers to address a wide array of fundamental questions in biology (Wu & al. 2008; Twyford & al. 2015). Linnaeus named the type species of Mimulus (ringens L.), while Darwin (1876) used Mimulus (luteus L.) to answer key research questions. The incredible phenotypic diversity of this group has made it the focus of ecological and evolutionary study since the mid-20th century, initiated by the influential work of Clausen, Keck, and Hiesey as well as their students and collaborators (Clausen & Hiesey 1958; Hiesey & al. 1971, Vickery 1952, 1978). Research has continued on this group of diverse taxa throughout the 20th and into the 21st century (Bradshaw & al. 1995; Schemske & Bradshaw 1999; Wu & al. 2008; Twyford & al. 2015; Yuan 2019), and Mimulus guttatus was one of the first non-model plants to be selected for full genome sequencing (Hellsten & al. 2013). Mimulus has played a key role in advancing our general understanding of the evolution of pollinator shifts (Bradshaw & Schemske 2003; Cooley & al. 2011; Byers & al. 2014), adaptation (Lowry & Willis 2010; Kooyers & al. 2015; Peterson & al. 2016; Ferris & Willis 2018; Troth & al. 2018), speciation (Ramsey & al. 2003; Wright & al. 2013; Sobel & Streisfeld 2015; Zuellig & Sweigart 2018), meiotic drive (Fishman & Saunders 2008), polyploidy (Vallejo-Marín 2012; Vallejo-Marín & al. 2015), range limits (Angert 2009; Sexton et al. 2011; Grossenbacher & al. 2014; Sheth & Angert 2014), circadian rhythms (Greenham & al. 2017), genetic recombination (Hellsten & al. 2013), mating systems (Fenster & Ritland 1994; Dudash & Carr 1998; Brandvain & al. 2014) and developmental biology (Moody & al. 1999; Baker & al. 2011, 2012; Yuan 2019). This combination of a rich history of study coupled with sustained modern research activity is unparalleled among angiosperms. Across many interested parties, the name Mimulus therefore takes on tremendous biological significance and is recognizable not only by botanists, but also by zoologists, horticulturalists, naturalists, and members of the biomedical community. Names associated with a taxonomic group of this prominence should have substantial inertia, and disruptive name changes should be avoided. As members of the Mimulus community, we advocate retaining the genus name Mimulus to describe all monkeyflowers. This is despite recent nomenclature changes that have led to a renaming of most monkeyflower species to other genera.Additional co-authors: Jannice Friedman, Dena L Grossenbacher, Liza M Holeski, Christopher T Ivey, Kathleen M Kay, Vanessa A Koelling, Nicholas J Kooyers, Courtney J Murren, Christopher D Muir, Thomas C Nelson, Megan L Peterson, Joshua R Puzey, Michael C Rotter, Jeffrey R Seemann, Jason P Sexton, Seema N Sheth, Matthew A Streisfeld, Andrea L Sweigart, Alex D Twyford, John H Willis, Kevin M Wright, Carrie A Wu, Yao-Wu Yua