Search bioRxiv⌕ Search

bioRxiv · 10.1101/2024.09.02.610915

A paleogenomic approach to reconstruct historical responses of coral reefs to anthropogenic change

Abstract

Coral reefs are declining worldwide due to anthropogenic environmental change. The foundation and health of these ecosystems rely on the harmonious functioning of all members of coral holobionts, i.e., cnidarian host, symbiotic microalgae, and associated microbiome. Coral stress responses often involve shifts in the taxonomic identity of their symbionts and microbiomes. Tracing back changes in coral holobiont composition over prolonged time periods can help us reconstruct health history of reefs and gain a better understanding of coral response to current stressors. Here, we focused on a major Caribbean reef-builder coral, Orbicella faveolata, from Varadero Reef, Colombia. This reef has undergone extensive freshwater sediment discharge and pollution for decades as result of urbanization. We show, for the first time, that paleogenomic and paleoclimatic approaches can be combined to reconstruct historical coral holobiont dynamics potentially associated with anthropogenic disturbances.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Gonzalez-Pech, R. A., Howe, C., Lizcano-Sandoval, L. D., Eisenhofer-Philipona, R. A., Marciniak, S., Roitman, S., Marulanda-Gomez, A. M., Rodriguez-Ramirez, A., Perry, G., Weyrich, L., Lopez-Victoria, M., Cole, J. E., Medina, M.. 2024-09-03. A paleogenomic approach to reconstruct historical responses of coral reefs to anthropogenic change. https://doi.org/10.1101/2024.09.02.610915

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Single-AAV-mediated cardiomyocyte-specific adenine base editing ameliorates cardiac hypertrophy in vivo

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disorder, frequently accompanied by cardiac hypercontractility, diastolic dysfunction, heart failure and sudden cardiac death. The disease is predominantly caused by pathogenic variants in genes encoding sarcomeric proteins and current therapeutic strategies largely focus on symptom management. Adeno-associated virus-based (AAV) delivery of base editing tools has emerged as an alternative strategy that acts directly on the genetic cause of disease. However, canonical SpCas9-based editors are too large to package into a single-AAV vector which mandates dual-AAV approaches that require higher overall vector doses with elevated toxicity risk and increased manufacturing costs. Here, we report the development and application of a single vector approach for cardiomyocyte-specific adenine base editing to correct a Dutch founder mutation in MYBPC3 (c.2827C>T, p.Arg943Ter) that causes HCM. We systematically compared compact base editors in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and selected the most efficient configuration, which reversed disease-associated hypercontractility in engineered human myocardium (EHM). To fit the editor/guide construct in a single-AAV vector, we screened a library of rationally designed small chimeric promoters and identified 6C2 to effectively drive expression in hiPSC-CMs and cardiac tissue of both mice and non-human primates (NHP) with exceptional specificity. Delivered in a single next-generation cardiotropic AAV capsid, we achieved therapeutic correction in an HCM mouse model at doses 20-fold below published dual-AAV cardiomyopathy base editing approaches. These results establish cardiomyocyte-specific, single vector-mediated base editing as a viable therapeutic strategy for inherited cardiomyopathies.

molecular biology↗

Engineered Miniature ParTasR Enables Efficient PAMless Genome Editing

TIGR-Tas system holds great promise for genome-engineering applications owing to its compact size and PAMless targeting capability. However, its low editing efficiency in mammalian cells severely limits its broader utility. Here, we engineered a highly active variant of ParTasR, termed eTasR, through structure-guided rational design of ParTasR combined with fusion to the exonuclease TREX2. eTasR increased mammalian editing efficiency from the original 4.29% to 48.94% with an average 26.52-fold increase, significantly surpassing the efficiency of SpRY, a reported version of PAM-free nuclease. More importantly, single-AAV delivery enabled efficient Hpd disruption in vivo, resulting in robust phenotypic rescue. Thus, eTasR provides a compact, PAMless and highly efficient platform for genome editing and therapeutic applications.

molecular biology↗

Enhancing pancreatic islet cell survival via NMDAR antagonist-driven ROR1 activation as revealed by phosphoproteomics

NMDA receptors (NMDARs) control function and survival not only of neurons, but also of insulin-producing pancreatic beta cells. Since insufficient insulin secretion and beta cell death are key events during diabetes development, targeting NMDARs offers a therapeutic approach. Specifically, the NMDAR antagonist dextrorphan (DXO) increases glucose-stimulated insulin secretion in clinical trials. Furthermore, treatment with DXO or optimized DXO derivatives prevents pancreatic islet cell death upon diabetogenic insults. Nonetheless, the signaling pathways induced by NMDAR inhibition are poorly understood. Here, we use complementary approaches, phosphoproteomics and tyrosine kinase profiling, to demonstrate that DXO and its derivatives rapidly regulate multiple intracellular signaling clusters, including mTOR and ERK signaling, in pancreatic islets. Notably, mTOR inhibition, but not ERK inhibition, is sufficient to negate DXO's protective effects. Further, we show that activation of Receptor Tyrosine Kinase-like Orphan Receptor 1 (ROR1) is a universal event upon NMDAR inhibition in islets. Simultaneous knockdown of Ror1/ROR1 and its paralogue Ror2/ROR2 compromises the viability of both mouse and human islets, highlighting the ROR1/2 signaling axis as a promising avenue for enhancing beta cell survival.

molecular biology↗