Illuminating Genetic Mysteries of the Dead Sea Scrolls.

The discovery of the 2,000-year-old Dead Sea Scrolls had an incomparable impact on the historical understanding of Judaism and Christianity. "Piecing together" scroll fragments is like solving jigsaw puzzles with an unknown number of missing parts. We used the fact that most scrolls are made from animal skins to "fingerprint" pieces based on DNA sequences. Genetic sorting of the scrolls illuminates their textual relationship and historical significance. Disambiguating the contested relationship between Jeremiah fragments supplies evidence that some scrolls were brought to the Qumran caves from elsewhere; significantly, they demonstrate that divergent versions of Jeremiah circulated in parallel throughout Israel (ancient Judea). Similarly, patterns discovered in non-biblical scrolls, particularly the Songs of the Sabbath Sacrifice, suggest that the Qumran scrolls represent the broader cultural milieu of the period. Finally, genetic analysis divorces debated fragments from the Qumran scrolls. Our study demonstrates that interdisciplinary approaches enrich the scholar's toolkit.

Physiological and Genetic Adaptations to Diving in Sea Nomads.

Understanding the physiology and genetics of human hypoxia tolerance has important medical implications, but this phenomenon has thus far only been investigated in high-altitude human populations. Another system, yet to be explored, is humans who engage in breath-hold diving. The indigenous Bajau people ("Sea Nomads") of Southeast Asia live a subsistence lifestyle based on breath-hold diving and are renowned for their extraordinary breath-holding abilities. However, it is unknown whether this has a genetic basis. Using a comparative genomic study, we show that natural selection on genetic variants in the PDE10A gene have increased spleen size in the Bajau, providing them with a larger reservoir of oxygenated red blood cells. We also find evidence of strong selection specific to the Bajau on BDKRB2, a gene affecting the human diving reflex. Thus, the Bajau, and possibly other diving populations, provide a new opportunity to study human adaptation to hypoxia tolerance. VIDEO ABSTRACT.

Structural insight into the allosteric inhibition of human sodium-calcium exchanger NCX1 by XIP and SEA0400.

Sodium-calcium exchanger proteins influence calcium homeostasis in many cell types and participate in a wide range of physiological and pathological processes. Here, we elucidate the cryo-EM structure of the human Na+/Ca2+ exchanger NCX1.3 in the presence of a specific inhibitor, SEA0400. Conserved ion-coordinating residues are exposed on the cytoplasmic face of NCX1.3, indicating that the observed structure is stabilized in an inward-facing conformation. We show how regulatory calcium-binding domains (CBDs) assemble with the ion-translocation transmembrane domain (TMD). The exchanger-inhibitory peptide (XIP) is trapped within a groove between the TMD and CBD2 and predicted to clash with gating helices TMs1/6 at the outward-facing state, thus hindering conformational transition and promoting inactivation of the transporter. A bound SEA0400 molecule stiffens helix TM2ab and affects conformational rearrangements of TM2ab that are associated with the ion-exchange reaction, thus allosterically attenuating Ca2+-uptake activity of NCX1.3.

Blue light promotes zero-valent sulfur production in a deep-sea bacterium.

Increasing evidence has shown that light exists in a diverse range of deep-sea environments. We unexpectedly found that blue light is necessary to produce excess zero-valent sulfur (ZVS) in Erythrobacter flavus 21-3, a bacterium that has been recently isolated from a deep-sea cold seep. E. flavus 21-3 is able to convert thiosulfate to ZVS using a novel thiosulfate oxidation pathway comprising a thiosulfate dehydrogenase (TsdA) and a thiosulfohydrolase (SoxB). Using proteomic, bacterial two-hybrid and heterologous expression assays, we found that the light-oxygen-voltage histidine kinase LOV-1477 responds to blue light and activates the diguanylate cyclase DGC-2902 to produce c-di-GMP. Subsequently, the PilZ domain-containing protein mPilZ-1753 binds to c-di-GMP and activates TsdA through direct interaction. Finally, Raman spectroscopy and gene knockout results verified that TsdA and two SoxB homologs cooperate to regulate ZVS production. As ZVS is an energy source for E. flavus 21-3, we propose that deep-sea blue light provides E. flavus 21-3 with a selective advantage in the cold seep, suggesting a previously unappreciated relationship between light-sensing pathways and sulfur metabolism in a deep-sea microorganism.

Stable germline transgenesis using the Minos Tc1/mariner element in the sea urchin Lytechinus pictus.

Stable transgenesis is a transformative tool in model organism biology. Although the sea urchin is one of the oldest animal models in cell and developmental biology, studies in this animal have largely relied on transient manipulation of wild animals, without a strategy for stable transgenesis. Here, we build on recent progress to develop a more genetically tractable sea urchin species, Lytechinus pictus, and establish a robust transgene integration method. Three commonly used transposons (Minos, Tol2 and piggyBac) were tested for non-autonomous transposition, using plasmids containing a polyubiquitin promoter upstream of a H2B-mCerulean nuclear marker. Minos was the only transposable element that resulted in significant expression beyond metamorphosis. F0 animals were raised to sexual maturity, and spawned to determine germline integration and transgene inheritance frequency, and to characterize expression patterns of the transgene in F1 progeny. The results demonstrate transgene transmission through the germline, the first example of a germline transgenic sea urchin and, indeed, of any echinoderm. This milestone paves the way for the generation of diverse transgenic resources that will dramatically enhance the utility, reproducibility and efficiency of sea urchin research.

Integrative multi-omics increase resolution of the sea urchin posterior gut gene regulatory network at single cell level.

Drafting gene regulatory networks (GRNs) requires embryological knowledge pertaining to the cell type families, information on the regulatory genes, causal data from gene knockdown experiments and validations of the identified interactions by cis-regulatory analysis. We use multi-omics involving next-generation sequencing (-seq) to obtain the necessary information for drafting Strongylocentrotus purpuratus posterior gut GRN. Here we present an update to the GRN using i) a single cell RNA-seq derived cell atlas highlighting the 2 day post fertilization (dpf) sea urchin gastrula cell type families, as well as the genes expressed at single cell level, ii) a set of putative cis-regulatory modules and transcription factor (TF) binding sites obtained from chromatin accessibility ATAC-seq data, and iii) interactions directionality obtained from differential bulk RNA-seq following knockdown of the TF Sp-Pdx1, a key regulator of gut patterning in sea urchins. Combining these datasets, we draft the GRN for the hindgut Sp-Pdx1 positive cells in the 2 dpf gastrula embryo. Overall, our data suggests the complex connectivity of the posterior gut GRN and increases the resolution of gene regulatory cascades operating within it.

The cellular basis of feeding-dependent body size plasticity in sea anemones.

Many animals share a lifelong capacity to adapt their growth rates and body sizes to changing environmental food supplies. However, the cellular and molecular basis underlying this plasticity remains only poorly understood. We therefore studied how the sea anemones Nematostella vectensis and Aiptasia (Exaiptasia pallida) respond to feeding and starvation. Combining quantifications of body size and cell numbers with mathematical modelling, we observed that growth and shrinkage rates in Nematostella are exponential, stereotypic and accompanied by dramatic changes in cell numbers. Notably, shrinkage rates, but not growth rates, are independent of body size. In the facultatively symbiotic Aiptasia, we show that growth and cell proliferation rates are dependent on the symbiotic state. On a cellular level, we found that >7% of all cells in Nematostella juveniles reversibly shift between S/G2/M and G1/G0 cell cycle phases when fed or starved, respectively. Furthermore, we demonstrate that polyp growth and cell proliferation are dependent on TOR signalling during feeding. Altogether, we provide a benchmark and resource for further investigating the nutritional regulation of body plasticity on multiple scales using the genetic toolkit available for Nematostella.

Local and global changes in cell density induce reorganisation of 3D packing in a proliferating epithelium.

Tissue morphogenesis is intimately linked to the changes in shape and organisation of individual cells. In curved epithelia, cells can intercalate along their own apicobasal axes, adopting a shape named 'scutoid' that allows energy minimization in the tissue. Although several geometric and biophysical factors have been associated with this 3D reorganisation, the dynamic changes underlying scutoid formation in 3D epithelial packing remain poorly understood. Here, we use live imaging of the sea star embryo coupled with deep learning-based segmentation to dissect the relative contributions of cell density, tissue compaction and cell proliferation on epithelial architecture. We find that tissue compaction, which naturally occurs in the embryo, is necessary for the appearance of scutoids. Physical compression experiments identify cell density as the factor promoting scutoid formation at a global level. Finally, the comparison of the developing embryo with computational models indicates that the increase in the proportion of scutoids is directly associated with cell divisions. Our results suggest that apico-basal intercalations appearing immediately after mitosis may help accommodate the new cells within the tissue. We propose that proliferation in a compact epithelium induces 3D cell rearrangements during development.

Emerging long-term trends and interdecadal cycles in Antarctic polynyas.

Polynyas, areas of open water embedded within sea ice, are a key component of ocean-atmosphere interactions that act as hotspots of sea-ice production, bottom-water formation, and primary productivity. The specific drivers of polynya dynamics remain, however, elusive and coupled climate models struggle to replicate Antarctic polynya activity. Here, we leverage a 44-y time series of Antarctic sea ice to elucidate long-term trends. We identify Antarctic-wide linear increases and a hitherto undescribed cyclical pattern of polynya activity across the Ross Sea region that potentially arises from interactions between the Amundsen Sea Low and Southern Annular Mode. While their specific drivers remain unknown, identifying these emerging patterns augments our capacity to understand the processes that influence sea ice. As we enter a potentially new age of Antarctic sea ice, this advance in understanding will, in turn, lead to more accurate predictions of environmental change, and its implications for Antarctic ecosystems.

Synchronous retreat of Thwaites and Pine Island glaciers in response to external forcings in the presatellite era.

Today, relatively warm Circumpolar Deep Water is melting Thwaites Glacier at the base of its ice shelf and at the grounding zone, contributing to significant ice retreat. Accelerating ice loss has been observed since the 1970s; however, it is unclear when this phase of significant melting initiated. We analyzed the marine sedimentary record to reconstruct Thwaites Glacier's history from the early Holocene to present. Marine geophysical surveys were carried out along the floating ice-shelf margin to identify core locations from various geomorphic settings. We use sedimentological data and physical properties to define sedimentary facies at seven core sites. Glaciomarine sediment deposits reveal that the grounded ice in the Amundsen Sea Embayment had already retreated to within ~45 km of the modern grounding zone prior to ca. 9,400 y ago. Sediments deposited within the past 100+ y record abrupt changes in environmental conditions. On seafloor highs, these shifts document ice-shelf thinning initiating at least as early as the 1940s. Sediments recovered from deep basins reflect a transition from ice proximal to slightly more distal conditions, suggesting ongoing grounding-zone retreat since the 1950s. The timing of ice-shelf unpinning from the seafloor for Thwaites Glacier coincides with similar records from neighboring Pine Island Glacier. Our work provides robust new evidence that glacier retreat in the Amundsen Sea was initiated in the mid-twentieth century, likely associated with climate variability.

Widespread seawater intrusions beneath the grounded ice of Thwaites Glacier, West Antarctica.

Warm water from the Southern Ocean has a dominant impact on the evolution of Antarctic glaciers and in turn on their contribution to sea level rise. Using a continuous time series of daily-repeat satellite synthetic-aperture radar interferometry data from the ICEYE constellation collected in March-June 2023, we document an ice grounding zone, or region of tidally controlled migration of the transition boundary between grounded ice and ice afloat in the ocean, at the main trunk of Thwaites Glacier, West Antarctica, a strong contributor to sea level rise with an ice volume equivalent to a 0.6-m global sea level rise. The ice grounding zone is 6 km wide in the central part of Thwaites with shallow bed slopes, and 2 km wide along its flanks with steep basal slopes. We additionally detect irregular seawater intrusions, 5 to 10 cm in thickness, extending another 6 km upstream, at high tide, in a bed depression located beyond a bedrock ridge that impedes the glacier retreat. Seawater intrusions align well with regions predicted by the GlaDS subglacial water model to host a high-pressure distributed subglacial hydrology system in between lower-pressure subglacial channels. Pressurized seawater intrusions will induce vigorous melt of grounded ice over kilometers, making the glacier more vulnerable to ocean warming, and increasing the projections of ice mass loss. Kilometer-wide, widespread seawater intrusion beneath grounded ice may be the missing link between the rapid, past, and present changes in ice sheet mass and the slower changes replicated by ice sheet models.

Significant challenges to the sustainability of the California coast considering climate change.

Climate change is an existential threat to the environmental and socioeconomic sustainability of the coastal zone and impacts will be complex and widespread. Evidence from California and across the United States shows that climate change is impacting coastal communities and challenging managers with a plethora of stressors already present. Widespread action could be taken that would sustain California's coastal ecosystems and communities. In this perspective, we highlight the main threat to coastal sustainability: the compound effects of episodic events amplified with ongoing climate change, which will present unprecedented challenges to the state. We present two key challenges for California's sustainability in the coastal zone: 1) accelerating sea-level rise combined with storm impacts, and 2) continued warming of the oceans and marine heatwaves. Cascading effects from these types of compounding events will occur within the context of an already stressed system that has experienced extensive alterations due to intensive development, resource extraction and harvesting, spatial containment, and other human use pressures. There are critical components that could be used to address these immediate concerns, including comanagement strategies that include diverse groups and organizations, strategic planning integrated across large areas, rapid implementation of solutions, and a cohesive and policy relevant research agenda for the California coast. Much of this has been started in the state, but the scale could be increased, and timelines accelerated. The ideas and information presented here are intended to help expand discussions to sharpen the focus on how to encourage sustainability of California's iconic coastal region.

Evolving Arctic maritime hazards: Declining sea ice and rising waves in the Northwest Passage.

The ongoing and projected retreat of Arctic sea ice has garnered international interest toward the utilization of Arctic maritime corridors for shipping, tourism, and development. Yet, with potential for increasing traffic in Arctic regions, it's important to consider additional environmental variables affected by climate change which may threaten maritime operations. Here, we use four climate model projections to produce ocean wave simulations and investigate the future magnitude and seasonality of sea ice risk coupled with wave hazards. Analyzing the potential 5 mo shipping season spanning July to November along the Northwest Passage maritime route between 2020 and 2070, our results show a substantial decline in sea ice risk over the analysis time period, resulting in near open-water conditions along the route for a 5 mo period by 2070. However, as seasonal ice coverage retreats, there is a significant upward trend in wave heights along the route during July and November, with the timing of the greatest wave height shifting away from September toward later in the season. This result is pertinent as the possibility of seasonally unprecedented extreme waves coupled with subfreezing late fall temperatures makes for an especially hazardous environment, thus emphasizing the importance of considering the interaction between evolving sea ice and interdependent hazards when predicting the risks and challenges faced by Arctic maritime operations.

A submerged Stone Age hunting architecture from the Western Baltic Sea.

The Baltic Sea basins, some of which only submerged in the mid-Holocene, preserve Stone Age structures that did not survive on land. Yet, the discovery of these features is challenging and requires cross-disciplinary approaches between archeology and marine geosciences. Here, we combine shipborne and autonomousunderwater vehicle hydroacoustic data with up to a centimeter range resolution, sedimentological samples, and optical images to explore a Stone Age megastructure located in 21 m water depth in the Bay of Mecklenburg, Germany. The structure is made of 1,673 individual stones which are usually less than 1 m in height, placed side by side over a distance of 971 m in a way that argues against a natural origin by glacial transport or ice push ridges. Running adjacent to the sunken shoreline of a paleolake (or bog), whose youngest phase was dated to 9,143 ±36 ka B.P., the stonewall was likely used for hunting the Eurasian reindeer (Rangifer tarandus) during the Younger Dryas or early Pre-Boreal. It was built by hunter-gatherer groups that roamed the region after the retreat of the Weichselian Ice Sheet. Comparable Stone Age megastructures have become known worldwide in recent times but are almost unknown in Europe. The site represents one of the oldest documented man-made hunting structures on Earth, and ranges among the largest known Stone Age structure in Europe. It will become important for understanding subsistence strategies, mobility patterns, and inspire discussions concerning the territorial development in the Western Baltic Sea region.

Climate migration amplifies demographic change and population aging.

The warnings of potential climate migration first appeared in the scientific literature in the late 1970s when increased recognition that disintegrating ice sheets could drive people to migrate from coastal cities. Since that time, scientists have modeled potential climate migration without integrating other population processes, potentially obscuring the demographic amplification of this migration. Climate migration could amplify demographic change-enhancing migration to destinations and suppressing migration to origins. Additionally, older populations are the least likely to migrate, and climate migration could accelerate population aging in origin areas. Here, we investigate climate migration under sea-level rise (SLR), a single climatic hazard, and examine both the potential demographic amplification effect and population aging by combining matrix population models, flood hazard models, and a migration model built on 40 y of environmental migration in the United States to project the US population distribution of US counties. We find that the demographic amplification of SLR for all feasible Representative Concentration Pathway-Shared Socioeconomic Pathway (RCP-SSP) scenarios in 2100 ranges between 8.6-28 M [5.7-53 M]-5.3 and 18 times the number of migrants (0.4-10 M). We also project significant aging of coastal areas as youthful populations migrate but older populations remain, accelerating population aging in origin areas. As the percentage of the population lost due to climate migration increases, the median age also increases-up to 10+ y older in some highly impacted coastal counties. Additionally, our population projection approach can be easily adapted to investigate additional or multiple climate hazards.

Contribution of anthropogenic aerosols to persistent La Niña-like conditions in the early 21st century.

The discrepancy between the observed lack of surface warming in the eastern equatorial Pacific and climate model projections of an El Niño-like warming pattern confronts the climate research community. While anthropogenic aerosols have been suggested as a cause, the prolonged cooling trend over the equatorial Pacific appears in conflict with Northern Hemisphere aerosol emission reduction since the 1980s. Here, using CESM, we show that the superposition of fast and slow responses to aerosol emission change-an increase followed by a decrease-can sustain the La Niña-like condition for a longer time than expected. The rapid adjustment of Hadley Cell to aerosol reduction triggers joint feedback between low clouds, wind, evaporation, and sea surface temperature in the Southeast Pacific, leading to a wedge-shaped cooling that extends to the central equatorial Pacific. Meanwhile, the northern subtropical cell gradually intensifies, resulting in equatorial subsurface cooling that lasts for decades.

How larvae and life cycles evolve.

Marine larvae have factored heavily in pursuits to understand the origin and evolution of animal life cycles. Recent comparisons of gene expression and chromatin state in different species of sea urchin and annelid show how evolutionary changes in embryonic gene regulation can lead to markedly different larval forms.

Voltage-gated sodium channel activity mediates sea urchin larval skeletal patterning through spatial regulation of Wnt5 expression.

Defining pattern formation mechanisms during embryonic development is important for understanding the etiology of birth defects and to inform tissue engineering approaches. In this study, we used tricaine, a voltage-gated sodium channel (VGSC) inhibitor, to show that VGSC activity is required for normal skeletal patterning in Lytechinus variegatus sea urchin larvae. We demonstrate that tricaine-mediated patterning defects are rescued by an anesthetic-insensitive version of the VGSC LvScn5a. Expression of this channel is enriched in the ventrolateral ectoderm, where it spatially overlaps with posterolaterally expressed Wnt5. We show that VGSC activity is required to spatially restrict Wnt5 expression to this ectodermal region that is adjacent and instructive to clusters of primary mesenchymal cells that initiate secretion of the larval skeleton as triradiates. Tricaine-mediated Wnt5 spatial expansion correlates with the formation of ectopic PMC clusters and triradiates. These defects are rescued by Wnt5 knockdown, indicating that the spatial expansion of Wnt5 is responsible for the patterning defects induced by VGSC inhibition. These results demonstrate a previously unreported connection between bioelectrical status and the spatial control of patterning cue expression during embryonic pattern formation.

An optimized Tet-On system for conditional control of gene expression in sea urchins.

Sea urchins and other echinoderms are important experimental models for studying developmental processes. The lack of approaches for conditional gene perturbation, however, has made it challenging to investigate the late developmental functions of genes that have essential roles during early embryogenesis and genes that have diverse functions in multiple tissues. The doxycycline-controlled Tet-On system is a widely used molecular tool for temporally and spatially regulated transgene expression. Here, we optimized the Tet-On system to conditionally induce gene expression in sea urchin embryos. Using this approach, we explored the roles the MAPK signaling plays in skeletogenesis by expressing genes that perturb the pathway specifically in primary mesenchyme cells during later stages of development. We demonstrated the wide utility of the Tet-On system by applying it to a second sea urchin species and in cell types other than the primary mesenchyme cells. Our work provides a robust and flexible platform for the spatiotemporal regulation of gene expression in sea urchins, which will considerably enhance the utility of this prominent model system.

Molecular compartmentalization in a syncytium: restricted mobility of proteins within the sea urchin skeletogenic mesenchyme.

Multinucleated cells, or syncytia, are found in diverse taxa. Their biological function is often associated with the compartmentalization of biochemical or cellular activities within the syncytium. How such compartments are generated and maintained is poorly understood. The sea urchin embryonic skeleton is secreted by a syncytium, and local patterns of skeletal growth are associated with distinct sub-domains of gene expression within the syncytium. For such molecular compartments to be maintained and to control local patterns of skeletal growth: (1) the mobility of TFs must be restricted to produce stable differences in the transcriptional states of nuclei within the syncytium; and (2) the mobility of biomineralization proteins must also be restricted to produce regional differences in skeletal growth. To test these predictions, we expressed fluorescently tagged forms of transcription factors and biomineralization proteins in sub-domains of the skeletogenic syncytium. We found that both classes of proteins have restricted mobility within the syncytium and identified motifs that limit their mobility. Our findings have general implications for understanding the functional and molecular compartmentalization of syncytia.