Biology subjects

Edwards, C. E.

Publications and source records attributed to Edwards, C. E..

6 recordsLinked to original sources

bioRxiv2020

The evolutionary assembly of forest communities along environmental gradients: recent diversification or sorting of pre-adapted clades?

O_LIBiogeographic events occurring in the deep past can contribute to the structure of modern ecological communities. However, little is known about how the emergence of environmental gradients shape the evolution of species that underlie community assembly. In this study, we address how the creation of novel environments lead to community assembly via two non-mutually exclusive processes: 1) the immigration and ecological sorting of pre-adapted clades (ISPC), and 2) recent adaptive diversification (RAD). We study these processes in the context of the elevational gradient created by the uplift of the Central Andes. C_LIO_LIWe develop a novel approach and method based on the decomposition of species turnover into within- and among-clade components, where clades correspond to lineages that originated before mountain uplift. Effects of ISPC and RAD can be inferred from how components of turnover change with elevation. We test our approach using data from over 500 Andean forest plots. C_LIO_LIWe found that species turnover between communities at different elevations is dominated by the replacement of clades that originated before the uplift of the Central Andes. C_LIO_LIOur results suggest that immigration and sorting of clades pre-adapted to montane habitats is the primary mechanism shaping communities across elevations. C_LI

ecology↗

bioRxiv2020

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↗

bioRxiv2020

SARS-CoV-2 D614G Variant Exhibits Enhanced Replication ex vivo and Earlier Transmission in vivo

The D614G substitution in the S protein is most prevalent SARS-CoV-2 strain circulating globally, but its effects in viral pathogenesis and transmission remain unclear. We engineered SARS-CoV-2 variants harboring the D614G substitution with or without nanoluciferase. The D614G variant replicates more efficiency in primary human proximal airway epithelial cells and is more fit than wildtype (WT) virus in competition studies. With similar morphology to the WT virion, the D614G virus is also more sensitive to SARS-CoV-2 neutralizing antibodies. Infection of human ACE2 transgenic mice and Syrian hamsters with the WT or D614G viruses produced similar titers in respiratory tissue and pulmonary disease. However, the D614G variant exhibited significantly faster droplet transmission between hamsters than the WT virus, early after infection. Our study demonstrated the SARS-CoV2 D614G substitution enhances infectivity, replication fitness, and early transmission.

microbiology↗

bioRxiv2020

Epigenomic patterns reflect irrigation and grafting in the grapevine clone 'Chambourcin'

Although DNA methylation has largely been shown to be stable in plants, mounting evidence indicates methylation patterns may reflect environmental sensitivity. Perennial plants experience seasonal and inter-annual environmental variation, and clonal replicates of some long-lived plants, including many perennial crops, survive in a broad range of environments. This makes perennial crops a compelling study system to investigate links between the plant epigenome and environmental variation. In this study, we used whole genome bisulfite sequencing and small RNA sequencing to characterize the epigenome in 12 clonal replicates of the winegrape cultivar Chambourcin. We asked whether DNA methylation varied in response to a full factorial combination of irrigation and grafting treatments. We found signatures of both irrigation and grafting in the Chambourcin epigenome, as well as compelling evidence for a unique interaction effect whereby grafting appeared to override or mitigate epigenomic changes associated with irrigation in ungrafted vines. These findings indicate that the epigenome responds to environmental and agronomic manipulations, suggesting the epigenome might be a mechanism underlying how long-lived, clonal plants respond at the molecular level to their environment. Further research is needed to assess the potential relevance of variation in DNA methylation to plant form and function, and to address the implications of environmentally-inducible patterns of DNA methylation on the adaptive capacity of long-lived woody perennials in nature and under cultivation.

genomics↗

bioRxiv2020

Progenitor identification and SARS-CoV-2 infection in long-term human distal lung organoid cultures

The distal lung contains terminal bronchioles and alveoli that facilitate gas exchange and is affected by disorders including interstitial lung disease, cancer, and SARS-CoV-2-associated COVID-19 pneumonia. Investigations of these localized pathologies have been hindered by a lack of 3D in vitro human distal lung culture systems. Further, human distal lung stem cell identification has been impaired by quiescence, anatomic divergence from mouse and lack of lineage tracing and clonogenic culture. Here, we developed robust feeder-free, chemically-defined culture of distal human lung progenitors as organoids derived clonally from single adult human alveolar epithelial type II (AT2) or KRT5+ basal cells. AT2 organoids exhibited AT1 transdifferentiation potential, while basal cell organoids progressively developed lumens lined by differentiated club and ciliated cells. Organoids consisting solely of club cells were not observed. Upon single cell RNA-sequencing (scRNA-seq), alveolar organoids were composed of proliferative AT2 cells; however, basal organoid KRT5+ cells contained a distinct ITGA6+ITGB4+ mitotic population whose proliferation segregated to a TNFRSF12Ahi subfraction. Clonogenic organoid growth was markedly enriched within the TNFRSF12Ahi subset of FACS-purified ITGA6+ITGB4+ basal cells from human lung or derivative organoids. In vivo, TNFRSF12A+ cells comprised ~10% of KRT5+ basal cells and resided in clusters within terminal bronchioles. To model COVID-19 distal lung disease, we everted the polarity of basal and alveolar organoids to rapidly relocate differentiated club and ciliated cells from the organoid lumen to the exterior surface, thus displaying the SARS-CoV-2 receptor ACE2 on the outwardly-facing apical aspect. Accordingly, basal and AT2 "apical-out" organoids were infected by SARS-CoV-2, identifying club cells as a novel target population. This long-term, feeder-free organoid culture of human distal lung alveolar and basal stem cells, coupled with single cell analysis, identifies unsuspected basal cell functional heterogeneity and exemplifies progenitor identification within a slowly proliferating human tissue. Further, our studies establish a facile in vitro organoid model for human distal lung infectious diseases including COVID-19-associated pneumonia.

cell biology↗

bioRxiv2020

A mouse-adapted SARS-CoV-2 model for the evaluation of COVID-19 medical countermeasures

Coronaviruses are prone to emergence into new host species most recently evidenced by SARS-CoV-2, the causative agent of the COVID-19 pandemic. Small animal models that recapitulate SARS-CoV-2 disease are desperately needed to rapidly evaluate medical countermeasures (MCMs). SARS-CoV-2 cannot infect wildtype laboratory mice due to inefficient interactions between the viral spike (S) protein and the murine ortholog of the human receptor, ACE2. We used reverse genetics to remodel the S and mACE2 binding interface resulting in a recombinant virus (SARS-CoV-2 MA) that could utilize mACE2 for entry. SARS-CoV-2 MA replicated in both the upper and lower airways of both young adult and aged BALB/c mice. Importantly, disease was more severe in aged mice, and showed more clinically relevant phenotypes than those seen in hACE2 transgenic mice. We then demonstrated the utility of this model through vaccine challenge studies in immune competent mice with native expression of mACE2. Lastly, we show that clinical candidate interferon (IFN) lambda-1a can potently inhibit SARS-CoV-2 replication in primary human airway epithelial cells in vitro, and both prophylactic and therapeutic administration diminished replication in mice. Our mouse-adapted SARS-CoV-2 model demonstrates age-related disease pathogenesis and supports the clinical use of IFN lambda-1a treatment in human COVID-19 infections.

microbiology↗