Evolutionary Insights into Cnidarian-Dinoflagellate Symbiosis from Natural Variation in Aiptasia Sea Anemones

Mutualistic associations between corals and symbiotic microalgae of the genus Symbiodium power tropical reef ecosystems, hotspots of marine biodiversity that buffer coastlines, support tourism- and fisheries-based economies, and offer untapped potential for discovery of novel pharmaceutical compounds. However, reef ecosystems are declining at an alarming rate, in large part due to severe episodes of coral bleaching, or breakdown of the coral-Symbiodinium symbiosis. The sea anemone Aiptasia has emerged as a laboratory model system for understanding coral-Symbiodinium interactions at multiple biological levels. To further develop Aiptasia as an evolutionary model system, the goal of my dissertation work was to characterize natural variation in Aiptasia-Symbiodinium symbioses by (1) examining genome-wide polymorphism among global anemone lineages, (2) experimentally evaluating natural variation in bleaching response, and (3) investigating patterns of genetic variation in natural populations across diverse abiotic environments. In Chapter 2, I use low-coverage genome skimming to investigate polymorphism in well-studied laboratory strains hosting diverse Symbiodinium, revealing that higher genetic diversity exists in Aiptasia from the Western Atlantic compared to a more globally distributed lineage. I further compare polymorphisms in sliding windows across the genome to identify candidate genes under balancing and positive selection based on patterns of heterozygosity, nucleotide diversity, and Tajima’s D. In Chapter 3, I characterize bleaching of Aiptasia lab strains to different stressors and discover significant variation in responses to acute heat stress but not to cold-shock. In Chapter 4, I examine potential relationships between abiotic environmental variation and genetic variation of anemone-Symbiodinium assemblages in the wild, at four locations in Caribbean Panama where long-term environmental datasets are available. High-throughput genotyping of anemone populations revealed the presence of a closely related cryptic species, Exaiptasia brasiliensis, and striking differences in anemone abundance, distribution, and patterns of symbiont association across environments. An Aiptasia sub-population specific to the Bocas del Toro Archipelago is described, with strong differentiation compared to the global population at several loci predicted to be important for mediating interactions with Symbiodinium. Analyses further suggest that the spatial extent of clonal reproduction in natural populations could be somewhat limited. Overall, Chapters 2-4 support a widespread global Aiptasia population distributed throughout tropical and subtropical latitudes with one or more diverged lineages, diversity of both host lineages and holobiont assemblages centered in the tropical Western Atlantic, and holobiont distribution patterns that may be strongly influenced by abiotic environment. Future studies leveraging natural variation in the Aiptasia model system described here hold great promise for advancing our fundamental knowledge of the evolution of symbiotic interactions in the sea.Keywords: genetics, cnidarian, genomics, bleaching, symbiosis, evolutio

Massard Prairie Restoration and Soil Microbiome Succession

We have initially sequenced soil microbial DNA from 4 restored and 4 virgin tallgrass prairie soil samples from Ben Geren Park and Massard Prairie (Fort Smith, AR), respectively. As expected, the soil microbiomes are distinct, with several lineages of nitrogen-fixing bacteria more common in virgin tall grass prairie. However, we predict that as restoration of tallgrass prairie in Ben Geren Park progresses, the soil microbiome of restored prairie will more closely mirror those of the virgin prairie

Genome-wide polymorphism and signatures of selection in the symbiotic sea anemone Aiptasia

Background: Coral reef ecosystems are declining in response to global climate change and anthropogenic impacts. Yet patterns of standing genetic variation within cnidarian species, a major determinant of adaptive potential, are virtually unknown at genome-scale resolution. We explore patterns of genome-wide polymorphism and identify candidate loci under selection in the sea anemone Aiptasia, an important laboratory model system for studying the symbiosis between corals and dinoflagellate algae of the genus Symbiodinium. Results: Low coverage genome sequencing revealed large genetic distances among globally widespread lineages, novel candidate targets of selection, and considerably higher heterozygosity than previously reported for Aiptasia. More than 670,000 single nucleotide polymorphisms were identified among 10 Aiptasia individuals including two pairs of genetic clones. Evolutionary relationships based on genome-wide polymorphism supported the current paradigm of a genetically distinct population from the US South Atlantic that harbors diverse Symbiodinium clades. However, anemones from the US South Atlantic demonstrated a striking lack of shared derived polymorphism. Heterozygosity was an important feature shaping nucleotide diversity patterns: at any given SNP site, more than a third of individuals genotyped were heterozygotes, and heterozygosity within individual genomes ranged from 0.37–0.58 %. Analysis of nonsynonymous and synonymous sites suggested that highly heterozygous regions are evolving under relaxed purifying selection compared to the rest of the Aiptasia genome. Genes previously identified as having elevated evolutionary rates in Aiptasia compared to other cnidarians were found in our study to be under strong purifying selection within Aiptasia. Candidate targets of selection, including lectins and genes involved in Rho GTPase signalling, were identified based on unusual signatures of nucleotide diversity, Tajima’s D, and heterozygosity compared to genome-wide averages. Conclusions: This study represents the first genome-wide analysis of Tajima’s D in a cnidarian. Our results shed light on patterns of intraspecific genome-wide polymorphism in a model for studies of coral-algae symbiosis and present genetic targets for future research on evolutionary and cellular processes in early-diverging metazoans.Keywords: heterozygosity, Cnidarian symbiosis, genome skimming, Symbiodinium, Tajima's

Mother-infant interactions and regional brain volumes in infancy: an MRI study

Background: It is generally agreed that the human brain is responsive to environmental influences, and that the male brain may be particularly sensitive to early adversity. However, this is largely based on retrospective studies of older children and adolescents exposed to extreme environments in childhood. Less is understood about how normative variations in parent-child interactions are associated with the development of the infant brain in typical settings. Method: To address this, we used magnetic resonance imaging to investigate the relationship between observational measures of mother-infant interactions and regional brain volumes in a community sample of 3-6 month old infants (N=39). In addition, we examined whether this relationship differed in male and female infants. Results: We found that lower maternal sensitivity was correlated with smaller subcortical grey matter volumes in the whole sample, and that this was similar in both sexes. However, male infants who showed greater levels of positive communication and engagement during early interactions had smaller cerebellar volumes. Conclusion These preliminary findings suggest that variations in mother-infant interaction dimensions are associated with differences in infant brain development. Although the study is cross-sectional and causation cannot be inferred, the findings reveal a dynamic interaction between brain and environment that may be important when considering interventions to optimize infant outcomes

Remodeling of the Cortical Structural Connectome in Posttraumatic Stress Disorder:Results from the ENIGMA-PGC PTSD Consortium

BACKGROUND: Posttraumatic stress disorder (PTSD) is accompanied by disrupted cortical neuroanatomy. We investigated alteration in covariance of structural networks associated with PTSD in regions that demonstrate the case-control differences in cortical thickness (CT) and surface area (SA). METHODS: Neuroimaging and clinical data were aggregated from 29 research sites in >1,300 PTSD cases and >2,000 trauma-exposed controls (age 6.2-85.2 years) by the ENIGMA-PGC PTSD working group. Cortical regions in the network were rank-ordered by effect size of PTSD-related cortical differences in CT and SA. The top-n (n = 2 to 148) regions with the largest effect size for PTSD > non-PTSD formed hypertrophic networks, the largest effect size for PTSD < non-PTSD formed atrophic networks, and the smallest effect size of between-group differences formed stable networks. The mean structural covariance (SC) of a given n-region network was the average of all positive pairwise correlations and was compared to the mean SC of 5,000 randomly generated n-region networks. RESULTS: Patients with PTSD, relative to non-PTSD controls, exhibited lower mean SC in CT-based and SA-based atrophic networks. Comorbid depression, sex and age modulated covariance differences of PTSD-related structural networks. CONCLUSIONS: Covariance of structural networks based on CT and cortical SA are affected by PTSD and further modulated by comorbid depression, sex, and age. The structural covariance networks that are perturbed in PTSD comport with converging evidence from resting state functional connectivity networks and networks impacted by inflammatory processes, and stress hormones in PTSD

A Comparison of Methods to Harmonize Cortical Thickness Measurements Across Scanners and Sites

Results of neuroimaging datasets aggregated from multiple sites may be biased by site-specific profiles in participants’ demographic and clinical characteristics, as well as MRI acquisition protocols and scanning platforms. We compared the impact of four different harmonization methods on results obtained from analyses of cortical thickness data: (1) linear mixed-effects model (LME) that models site-specific random intercepts (LME INT), (2) LME that models both site-specific random intercepts and age-related random slopes (LME INT+SLP), (3) ComBat, and (4) ComBat with a generalized additive model (ComBat-GAM). Our test case for comparing harmonization methods was cortical thickness data aggregated from 29 sites, which included 1,340 cases with posttraumatic stress disorder (PTSD) (6.2–81.8 years old) and 2,057 trauma-exposed controls without PTSD (6.3–85.2 years old). We found that, compared to the other data harmonization methods, data processed with ComBat-GAM was more sensitive to the detection of significant case-control differences (Χ 2(3) = 63.704, p < 0.001) as well as case-control differences in age-related cortical thinning (Χ 2(3) = 12.082, p = 0.007). Both ComBat and ComBat-GAM outperformed LME methods in detecting sex differences (Χ 2(3) = 9.114, p = 0.028) in regional cortical thickness. ComBat-GAM also led to stronger estimates of age-related declines in cortical thickness (corrected p-values < 0.001), stronger estimates of case-related cortical thickness reduction (corrected p-values < 0.001), weaker estimates of age-related declines in cortical thickness in cases than controls (corrected p-values < 0.001), stronger estimates of cortical thickness reduction in females than males (corrected p-values < 0.001), and stronger estimates of cortical thickness reduction in females relative to males in cases than controls (corrected p-values < 0.001). Our results support the use of ComBat-GAM to minimize confounds and increase statistical power when harmonizing data with non-linear effects, and the use of either ComBat or ComBat-GAM for harmonizing data with linear effects

Ten people‐centered rules for socially sustainable ecosystem restoration

As the UN Decade on Ecosystem Restoration begins, there remains insufficient emphasis on the human and social dimensions of restoration. The potential that restoration holds for achieving both ecological and social goals can only be met through a shift toward people-centered restoration strategies. Toward this end, this paper synthesizes critical insights from a special issue on “Restoration for whom, by whom” to propose actionable ways to center humans and social dimensions in ecosystem restoration, with the aim of generating fair and sustainable initiatives. These rules respond to a relative silence on socio-political issues in di Sacco et al.'s “Ten golden rules for reforestation to optimize carbon sequestration, biodiversity recovery and livelihood benefits” on socio-political issues and offer complementary guidance to their piece. Arranged roughly in order from pre-intervention, design/initiation, implementation, through the monitoring, evaluation and learning phases, the 10 people-centered rules are: (1) Recognize diversity and interrelations among stakeholders and rightsholders'; (2) Actively engage communities as agents of change; (3) Address socio-historical contexts; (4) Unpack and strengthen resource tenure for marginalized groups; (5) Advance equity across its multiple dimensions and scales; (6) Generate multiple benefits; (7) Promote an equitable distribution of costs, risks, and benefits; (8) Draw on different types of evidence and knowledge; (9) Question dominant discourses; and (10) Practice inclusive and holistic monitoring, evaluation, and learning. We contend that restoration initiatives are only tenable when the issues raised in these rules are respectfully addressed

The effects of CRF antagonists, antalarmin, CP154,526, LWH234, and R121919, in the forced swim test and on swim-induced increases in adrenocorticotropin in rats

Exposure to extreme stress has been suggested to produce long-term, detrimental alterations in the hypothalamic–pituitary–adrenal (HPA) axis leading to the development of mental disorders such as depression. Therefore, compounds that block the effects of stress hormones were investigated as potential therapeutics for depression.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46365/1/213_2005_Article_2164.pd

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant