Using Landscape Genetics To Assess Population Connectivity In A Habitat Generalist

Understanding the nature of genetic variation in natural populations is an underlying theme of population genetics. In recent years population genetics has benefited from the incorporation of landscape and environmental data into pre-existing models of isolation by distance (IBD) to elucidate features influencing spatial genetic variation. Many of these landscape genetics studies have focused on populations separated by discrete barriers (e.g., mountain ridges) or species with specific habitat requirements (i.e., habitat specialists). One difficulty in using a landscape genetics approach for taxa with less stringent habitat requirements (i.e., generalists) is the lack of obvious barriers to gene flow and preference for specific habitats. My study attempts to fill this information gap to understand mechanisms underlying population subdivision in generalists, using the squirrel treefrog (Hyla squirella) and a system for classifying ‗terrestrial ecological systems‘ (i.e. habitat types). I evaluate this dataset with microsatellite markers and a recently introduced method based on ensemble learning (Random Forest) to identify whether spatial distance, habitat types, or both have influenced genetic connectivity among 20 H. squirella populations. Next, I hierarchically subset the populations included in the analysis based on (1) genetic assignment tests and (2) Mantel correlograms to determine the relative role of spatial distance in shaping landscape genetic patterns. Assignment tests show evidence of two genetic clusters that separate populations in Florida‘s panhandle (Western cluster) from those in peninsular Florida and southern Georgia (Eastern cluster). Mantel correlograms suggest a patch size of approximately 150 km. Landscape genetic analyses at all three spatial scales yielded improved model fit relative to isolation by distance when including habitat types. A hierarchical effect was identified whereby the importance of spatial distance (km) was the strongest predictor of patterns of genetic differentiation above the scale of the genetic patch. Below the genetic patch, spatial distance was still an explanatory variable but was only iv approximately 30% as relevant as mesic flatwoods or upland oak hammocks. Thus, it appears that habitat types largely influence patterns of population genetic connectivity at local scales but the signal of IBD becomes the dominant driver of regional connectivity. My results highlight some habitats as highly relevant to increased genetic connectivity at all spatial scales (e.g., upland oak hammocks) while others show no association (e.g., silviculture) or scale specific associations (e.g., pastures only at global scales). Given these results it appears that treating habitat as a binary metric (suitable/non-suitable) may be overly simplistic for generalist species in which gene flow probably occurs in a spectrum of habitat suitability. The overall pattern of spatial genetic and landscape genetic structure identified here provides insight into the evolutionary history and patterns of population connectivity for H. squirella and improves our understanding of the role of matrix composition for habitat generalists

Systemic Tissue and Cellular Disruption from SARS-CoV-2 Infection revealed in COVID- 19 Autopsies and Spatial Omics Tissue Maps

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus has infected over 115 million people and caused over 2.5 million deaths worldwide. Yet, the molecular mechanisms underlying the clinical manifestations of COVID-19, as well as what distinguishes them from common seasonal influenza virus and other lung injury states such as Acute Respiratory Distress Syndrome (ARDS), remains poorly understood. To address these challenges, we combined transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues, matched with spatial protein and expression profiling (GeoMx) across 357 tissue sections. These results define both body-wide and tissue-specific (heart, liver, lung, kidney, and lymph nodes) damage wrought by the SARS-CoV-2 infection, evident as a function of varying viral load (high vs. low) during the course of infection and specific, transcriptional dysregulation in splicing isoforms, T cell receptor expression, and cellular expression states. In particular, cardiac and lung tissues revealed the largest degree of splicing isoform switching and cell expression state loss. Overall, these findings reveal a systemic disruption of cellular and transcriptional pathways from COVID-19 across all tissues, which can inform subsequent studies to combat the mortality of COVID-19, as well to better understand the molecular dynamics of lethal SARS-CoV-2 infection and other viruses

Goldilocks Meets Santa Rosalia: An Ephemeral Speciation Model Explains Patterns of Diversification Across Time Scales

Understanding the rate at which new species form is a key question in studying the evolution of life on earth. Here we review our current understanding of speciation rates, focusing on studies based on the fossil record, phylogenies, and mathematical models. We find that speciation rates estimated from these different studies can be dramatically different: some studies find that new species form quickly and often, while others find that new species form much less frequently. We suggest that instead of being contradictory, differences in speciation rates across different scales can be reconciled by a common model. Under the “ephemeral speciation model”, speciation is very common and very rapid but the new species produced almost never persist. Evolutionary studies should therefore focus on not only the formation but also the persistence of new species

System-wide transcriptome damage and tissue identity loss in COVID-19 patients

The molecular mechanisms underlying the clinical manifestations of coronavirus disease 2019 (COVID-19), and what distinguishes them from common seasonal influenza virus and other lung injury states such as acute respiratory distress syndrome, remain poorly understood. To address these challenges, we combine transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues to define body-wide transcriptome changes in response to COVID-19. We then match these data with spatial protein and expression profiling across 357 tissue sections from 16 representative patient lung samples and identify tissue-compartment-specific damage wrought by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, evident as a function of varying viral loads during the clinical course of infection and tissue-type-specific expression states. Overall, our findings reveal a systemic disruption of canonical cellular and transcriptional pathways across all tissues, which can inform subsequent studies to combat the mortality of COVID-19 and to better understand the molecular dynamics of lethal SARS-CoV-2 and other respiratory infections., • Across all organs, fibroblast, and immune cell populations increase in COVID-19 patients • Organ-specific cell types and functional markers are lost in all COVID-19 tissue types • Lung compartment identity loss correlates with SARS-CoV-2 viral loads • COVID-19 uniquely disrupts co-occurrence cell type clusters (different from IAV/ARDS) , Park et al. report system-wide transcriptome damage and tissue identity loss wrought by SARS-CoV-2, influenza, and bacterial infection across multiple organs (heart, liver, lung, kidney, and lymph nodes) and provide a spatiotemporal landscape of COVID-19 in the lung

SARS-CoV-2 infection produces chronic pulmonary epithelial and immune cell dysfunction with fibrosis in mice

A subset of individuals who recover from coronavirus disease 2019 (COVID-19) develop post-acute sequelae of SARS-CoV-2 (PASC), but the mechanistic basis of PASC-associated lung abnormalities suffers from a lack of longitudinal tissue samples. The mouse-adapted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain MA10 produces an acute respiratory distress syndrome (ARDS) in mice similar to humans. To investigate PASC pathogenesis, studies of MA10-infected mice were extended from acute to clinical recovery phases. At 15 to 120 days post-virus clearance, pulmonary histologic findings included subpleural lesions composed of collagen, proliferative fibroblasts, and chronic inflammation, including tertiary lymphoid structures. Longitudinal spatial transcriptional profiling identified global reparative and fibrotic pathways dysregulated in diseased regions, similar to human COVID-19. Populations of alveolar intermediate cells, coupled with focal up-regulation of pro-fibrotic markers, were identified in persistently diseased regions. Early intervention with antiviral EIDD-2801 reduced chronic disease, and early anti-fibrotic agent (nintedanib) intervention modified early disease severity. This murine model provides opportunities to identify pathways associated with persistent SARS-CoV-2 pulmonary disease and test countermeasures to ameliorate PASC., After recovery from acute SARS-CoV-2 infection, mice exhibit chronic lung disease similar to some humans, allowing for testing of therapeutics

Genetic Networks, Adaptation, and the Evolution of Genomic Islands of Divergence

Organic fertilizers, such as dairy manure and biosolids, are often applied to agricultural fields as nutrient amendments. In addition to essential nutrients, organic fertilizers regularly contain chemicals of emerging concern (CEC) including hormones, phytoestrogens, antibiotics, pharmaceuticals, and metals. In this thesis, I explore the prevalence of CECs in Idaho's dairy manure and biosolids and their environmental fate from land-application of organic fertilizers. Two dairy manure samples and one biosolid sample were extracted for 27 CECS, and antibiotics and hormones were detected in all three samples. Undisturbed soil columns were used to determine the environmental mobility of CECs through an agricultural soil. Sulfonamides, flunixin, and ibuprofen eluted from the chemical-treated columns, but no flush of hormones was detected. The continued application of organic fertilizers may pose a threat to future public and environmental health due to the frequent presence of some CECs.Thesis (Ph.D., Bioinformatics & Computational Biology) -- University of Idaho, 201

Uplift and erosion of genomic islands with standing genetic variation

AbstractDetails of the processes that generate biological diversity have long been of interest to evolutionary biologists. A common theme in nature is diversification via divergent selection with gene flow. Empirical studies on this topic find variable genetic differentiation throughout the genome, that genetic differentiation is non-randomly distributed, and that loci of adaptive significance are often found clustered together within “genomic islands of divergence”. Theoretical models based on new mutations show how these genomic islands can arise and grow as a result of a complex interaction of various evolutionary and genic processes. In the current study, I ask if such genomic islands can alternatively arise from divergent selection from standing genetic variation and I tested this using a simple two locus model of selection. There are numerous ways in which standing genetic variation can be partitioned (e.g., between alleles, between loci, and between populations) and I tested which of these scenarios can give rise to an island pattern compared to no genomic differentiation or complete genomic differentiation. I found that divergent selection, even without reciprocal gene exchange between populations, following a bout of admixture can relatively quickly produce an island pattern. Moreover, I found two pathways in which islands can form from divergence from standing variation: 1) through the build up of islands and 2) through the breakdown of larger, genome-wide differentiation. Lastly, similar to new mutation theory, I found that the frequency of recombination is an important determinant of island formation from standing genetic variation such that mating behavior of a species (e.g., facultative or obligate sexual) can impact the likelihood of island formation.</jats:p

GENETIC REGULATORY NETWORK MOTIFS CONSTRAIN ADAPTATION THROUGH CURVATURE IN THE LANDSCAPE OF MUTATIONAL (CO)VARIANCE

Systems biology is accumulating a wealth of understanding about the structure of genetic regulatory networks, leading to a more complete picture of the complex genotype-phenotype relationship. However, models of multivariate phenotypic evolution based on quantitative genetics have largely not incorporated a network-based view of genetic variation. Here we model a set of two-node, two-phenotype genetic network motifs, covering a full range of regulatory interactions. We find that network interactions result in different patterns of mutational (co)variance at the phenotypic level (the M-matrix), not only across network motifs but also across phenotypic space within single motifs. This effect is due almost entirely to mutational input of additive genetic (co)variance. Variation in M has the effect of stretching and bending phenotypic space with respect to evolvability, analogous to the curvature of space-time under general relativity, and similar mathematical tools may apply in each case. We explored the consequences of curvature in mutational variation by simulating adaptation under divergent selection with gene flow. Both standing genetic variation (the G-matrix) and rate of adaptation are constrained by M, so that G and adaptive trajectories are curved across phenotypic space. Under weak selection the phenotypic mean at migration-selection balance also depends on M

Data from: Genetic regulatory network motifs constrain adaptation through curvature in the landscape of mutational (co)variance

Systems biology is accumulating a wealth of understanding about the structure of genetic regulatory networks, leading to a more complete picture of the complex genotype-phenotype relationship. However, models of multivariate phenotypic evolution based on quantitative genetics have largely not incorporated a network-based view of genetic variation. Here we model a set of two-node, two-phenotype genetic network motifs, covering a full range of regulatory interactions. We find that network interactions result in different patterns of mutational (co)variance at the phenotypic level (the M-matrix), not only across network motifs but also across phenotypic space within single motifs. This effect is due almost entirely to mutational input of additive genetic (co)variance. Variation in M has the effect of stretching and bending phenotypic space with respect to evolvability, analogous to the curvature of space-time under general relativity, and similar mathematical tools may apply in each case. We explored the consequences of curvature in mutational variation by simulating adaptation under divergent selection with gene flow. Both standing genetic variation (the G-matrix) and rate of adaptation are constrained by M, so that G and adaptive trajectories are curved across phenotypic space. Under weak selection the phenotypic mean at migration-selection balance also depends on M

Code and simulation output

This tar.gz file contains directories with R code and simulation output for all figures and data described in the paper. See the README.pdf file for a full description of contents