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Meyer, E. M.

Publications and source records attributed to Meyer, E. M..

4 recordsLinked to original sources

Traits and hidden states: is self-fertilization associated with rates of diversification across mating and sexual systems?

Reproductive biology is a key determinant of fitness. State-dependent speciation-extinction methods (SSEs) are often used to associate traits with patterns of diversification. Previously, SSEs have been used within families to investigate the hypothesis that selfing is an evolutionary "dead end." To the best of the authors knowledge, no study has looked across families, which would increase power to more generally test this hypothesis. Here, we examine the impact of 1) mating system and 2) sexual system on diversification across 18 phylogenetically diverse families. We also discuss how more recent advances in SSE models (i.e., "hidden state" and tree-only models) influence our interpretation of these patterns and evaluate how the relationship between mating and sexual systems can be leveraged to gain insight into the impact of reproductive biology on evolutionary outcomes. In this study, we find that the mating system as a trait does not better explain patterns of diversification when compared to null models, but the sexual system often does. We also find family-level heterogeneity in our results, which suggests conclusions drawn from studies on individual families may not be consistent with any broader trend.

evolutionary biology↗

SARC028 samples reveal an interplay between TGF-beta, interferon signaling and low HLA class I expression as contributors to Ewing sarcoma checkpoint blockade resistance

PurposeEwing sarcoma, in contrast to some adult sarcoma subtypes, generally does not respond to single agent immunotherapy targeting PD1. The features of Ewing sarcoma that preclude the effectiveness of immunotherapy remain largely unknown. To address this question, we utilized biopsies from patients with Ewing sarcoma obtained pre- and post-pembrolizumab (anti-PD1) therapy from the phase 2 clinical trial SARC028 to interrogate the Ewing tumor microenvironment and features associated with resistance to checkpoint inhibition. Experimental DesignWe utilize multiplexed immunofluorescence, spatial proteomics and spatial transcriptomics to analyze paired pre- and 8 weeks post-treatment biopsy specimens from patients with Ewing sarcoma enrolled on SARC028. ResultsPembrolizumab therapy did not alter the quantity of immune cell infiltration in Ewing tumor biopsies. Analysis of tumor-associated protein markers revealed increased immunoregulatory markers after pembrolizumab. Spatial transcriptomics identified ten cellular neighborhoods (CN) across patients consisting of specific cell subsets. CN10 was consistently observed across patients with poor response. This cellular neighborhood was enriched for a tumor subpopulation with high TGF-{beta} response, low interferon (IFN) response, and low HLA class I expression. IFN response, HLA class I expression, and overall immune infiltration were correlated. ConclusionsAnalyses of the tumor microenvironment from Ewing sarcoma biopsies reveals an immunosuppressive triad, the disruption of which should be pursued to improve antitumor immunity. This work highlights the unique insight that can be gained from the analysis of paired patient Ewing sarcoma tumor biopsy samples from clinical trials. Statement of translational relevanceSingle agent checkpoint inhibitors have demonstrated limited clinical benefit in bone sarcomas, including Ewing sarcoma (EwS). While in vitro and limited patient tumor analyses have suggested mechanisms of immunotherapy resistance in EwS, tumor biopsies following checkpoint inhibitor administration have not been examined. SARC028 was a phase II study investigating blockade of programmed cell death-1 (PD-1) in patients with relapsed/refractory sarcomas, including EwS. Tumor biopsies were collected prior to and 8 weeks after anti-PD1 therapy. Here, we leverage a unique opportunity to understand EwS immunotherapy resistance through analysis of paired tumor samples from SARC028. Using a multi-omics approach, we identify features of EwS that contribute to primary resistance to anti-PD1 including TGF-{beta}, reduced interferon signaling and low HLA class I expression. This study provides an improved understanding of tumor characteristics driving poor response to immunotherapy in relapsed EwS and will guide the development of future trials to modulate this immunosuppressive axis.

cancer biology↗

The evolutionary dynamics of plant mating systems: how bias for studying 'interesting' plant reproductive systems could backfire

Background and AimsAn "abominable mystery": angiosperm sexual systems have been a source of both interest and frustration for the botanical community since Darwin. The evolutionary stability, overall frequency, and distribution of self-fertilization and mixed-mating systems have been explored in a variety of studies. However, there has been no recent study which directly addresses our knowledge of mating systems across families, the adequacy of existing data, or the potential for biases. ScopeHere we present an updated dataset of mating systems across flowering plants covering 6,781 species and 212 families based on a synthesis of existing reviews and an original literature review using Web of Science. We assess the adequacy of this data by evaluating for bias indicating enrichment of certain families or sexual systems. Key ResultsWe find that the vast majority of our data on mating systems comes from a small number of disproportionally sampled families, and that families with significant proportions of dioecious or monoecious species are much more likely to be undersampled. ConclusionsOur results show that the frequency of selfing in angiosperms is overestimated, possibly due to increased research interest in selfing and mixed-mating systems. This suggests that systematic study bias may mean we know less about this vital facet of plant life than we think.

evolutionary biology↗

Understanding how an amphicarpic species with a mixed mating system responds to fire: a population genetic approach

Amphicarphic species produce both aboveground and belowground seeds; the belowground seeds have been proposed to be an adaptation to disturbed sites because they are protected belowground, enabling them to persist and recolonize a site after disturbance. However, it is unknown whether such seeds indeed serve as the main colonizers after a disturbance. The amphicarpic species Polygala lewtonii is endemic to fire-prone Florida sandhill and scrub and is among only a few species with three flower types (aboveground chasmogamous flowers and both above and belowground cleistogamous flowers). The goal of this study was to understand whether recolonization of sites by P. lewtonii was accomplished primarily through germination of belowground seed. First, we quantified the outcrossing rate in seeds produced by aboveground chasmogamous flowers to determine whether we could detect differences in colonization of between seeds produced aboveground vs. belowground. Approximately 25% of seeds from aboveground chasmogamous flowers showed evidence of cross pollination and the seeds showed greater heterozygosity and lower inbreeding coefficients than pure selfing, indicating that it is possible to differentiate between selfed and non-selfed seed types in postfire colonization. Second, we analyzed genetic diversity, inbreeding, and genetic structure of the populations before and after a prescribed fire. If heterozygosity and admixture increased, and spatial population genetic structure and inbreeding decreased, this would indicate that fire promoted germination of outcrossed seed from aboveground flowers. However, inbreeding increased and spatial genetic structure and admixture decreased after fire, suggesting that selfed seed produced by belowground flowers predominantly recolonized the site after fire. Thus, amphicarpy is a powerful adaptation to fire-maintained environments by producing seeds that are well suited to the range of conditions presented by a highly variable, disturbance prone habitat.

plant biology↗