Biology subjects

Law, K.

Publications and source records attributed to Law, K..

4 recordsLinked to original sources

bioRxiv2024

Species Distribution of Cannabis sativa: Past, Present and future

Cannabis sativa L. is an annual flowering herb of Eurasian origin that has long been associated with humans. Domesticated independently at multiple locations at different times for different purposes (food, fiber, and medicine), these long-standing human associations have influenced its distribution. However, changing environmental conditions and climatic fluctuations have also contributed to the distribution of the species and define where it is optimally cultivated. Here we explore the shifts in distribution that C. sativa may have experienced in the past and explore the likely shifts in the future. Modeling under paleoclimatic scenarios shows niche expansion and contraction in Eurasia through the timepoints examined. Temperature and precipitation variables and soil variable data were combined for species distribution modeling in the present day and showed high and improved predictive ability together as opposed to when examined in isolation. The five most important variables explaining [~]65% of the total variation were soil organic carbon content (ORCDRC), pH index measured in water solution (PHIHOX), annual mean temperature (BIO-1), mean temperature of the coldest quarter (BIO-11) and soil organic carbon density (OCDENS) (AUC = 0.934). Climate model projections where efforts are made to curb emissions (RCP45/SSP245) and the business as usual (RCP85/SSP585) models were evaluated. Under projected future climate scenarios, shifts worldwide are predicted with a loss of [~]43% in suitability areas with scores above 0.4 observed by 2050 and continued but reduced rates of loss by 2070. Changes in habitat range have large implications for the conservation of wild relatives as well as for the cultivation of Cannabis as the industry moves toward outdoor cultivation practices.

plant biology↗

bioRxiv2024

Autism gene variants disrupt enteric neuron migration and cause gastrointestinal dysmotility

The comorbidity of autism spectrum disorders and severe gastrointestinal symptoms is well-established, yet the molecular underpinnings remain unknown. The identification of high-confidence large-effect autism risk genes offers the opportunity to identify convergent, underlying biology by studying these genes in the context of the gastrointestinal system. Here we show that the expression of these genes is enriched in human prenatal gut neurons as well as their migratory progenitors, suggesting that the development and/or function of these neurons may be disrupted by autism-associated pathogenic variants, leading to gastrointestinal dysfunction. Here we document the prevalence of gastrointestinal issues in patients with large-effect variants in sixteen of these genes, highlighting dysmotility, consistent with potential enteric neuron dysfunction. Using the high-throughput diploid frog Xenopus tropicalis, we individually target five of these genes (SYNGAP1, CHD8, SCN2A, CHD2, and DYRK1A) and observe disrupted enteric neuronal progenitor migration for each. More extensive analysis of DYRK1A reveals that perturbation causes gut dysmotility in vivo, which can be ameliorated by treatment with a selective serotonin reuptake inhibitor (escitalopram) or a serotonin receptor 6 agonist, identified by in vivo drug screening. This work suggests that atypical development of enteric neurons contributes to the gastrointestinal distress commonly seen in individuals with autism and that increasing serotonin signaling may be a productive therapeutic avenue.

neuroscience↗

bioRxiv2022

Pleiotropy of autism-associated chromatin regulators

Gene ontology analyses of high confidence autism spectrum disorder (hcASD) risk genes have historically highlighted chromatin regulation and synaptic function as major contributors to pathobiology. Our recent functional work in vivo has additionally implicated microtubule biology and identified disrupted cellular proliferation as a convergent ASD phenotype. As many chromatin regulators, including ASD risk genes ADNP and CHD3, are known to directly regulate both tubulins and histones, we studied the five chromatin regulators most strongly associated with ASD (ADNP, CHD8, CHD2, POGZ, and SUV420H1/KMT5B) specifically with respect to microtubule biology. We observe that all five localize to microtubules of the mitotic spindle in vitro and in vivo. Further in-depth investigation of CHD2 provides evidence that patient-derived mutations lead to a range of microtubule-related phenotypes, including disrupted localization of the protein at the mitotic spindle, spindle defects, cell cycle stalling, DNA damage, and cell death. Lastly, we observe that ASD genetic risk is significantly enriched among microtubule-associated proteins, suggesting broader relevance. Together, these results provide further evidence that the role of tubulin biology and cellular proliferation in ASD warrant further investigation and highlight the pitfalls of relying solely on annotated gene functions in the search for pathological mechanisms.

developmental biology↗

bioRxiv2022

Phylogenetic resolution of the Cannabis genus reveals extensive admixture

Population structure of Cannabis sativa L. was explored across nine independent collections that each contained a unique sampling of varieties. Hierarchical Clustering of Principal Components (HCPC) identified a range of three to seven genetic clusters across datasets with inconsistent structure based on use type indicating the importance of sampling particularly when there is limited passport data. There was broader genetic diversity in modern cultivars relative to landraces. Further, in a subset of geo-referenced landrace accessions, population structure was observed based on geography. The inconsistent structure across different collections shows the complexity within Cannabis, and the importance of understanding any particular collection which could then be leveraged in breeding programs for future crop improvement.

genomics↗