Biology subjects

Sanger, A.

Publications and source records attributed to Sanger, A..

4 recordsLinked to original sources

bioRxiv2026

Tracing the evolution of microbial alkaline phosphatases and their role in phosphorus recycling through time

Phosphorus (P) recycling in seawater is critical for maintaining nutrient availability and marine primary productivity. This process is catalyzed by alkaline phosphatases enzymes, which hydrolyze dissolved organic phosphorus (DOP) compounds, releasing inorganic P for cellular assimilation. Here, we reconstructed the evolutionary history of three major alkaline phosphatase families through deep time using phylogenetic reconciliation across the tree of life. We further quantified their distribution and cellular localization across major metabolic groups using extant genomes to assess how the oceans capacity for P regeneration has changed through time. Our results demonstrate that alkaline phosphatases emerged early in the Archaean, indicating that DOP has sustained marine ecosystems for most of Earths history. A pronounced expansion and diversification of alkaline phosphatases occurred during the Neoproterozoic, coinciding with the rise and ecological diversification of algae. Across metabolic groups, extracellular alkaline phosphatases are particularly concentrated in ferric iron reducers, fermenters, and aerobic heterotrophs, but are comparatively rare in other metabolisms. This distribution suggests that the efficiency of marine P recycling has been strongly influenced by prevailing metabolic strategies and environmental redox conditions. Overall, our results provide new insights into the enzymatic drivers of marine P cycling and the mechanisms that maintained marine productivity as Earths surface became progressively oxygenated and biologically complex.

microbiology↗

bioRxiv2025

Microbial exoenzymes catalyzed the transition to an oxygenated Earth

Microbial exoenzymes--extracellular enzymes secreted to degrade complex organic polymers-- are essential for recycling carbon and nutrients, thus sustaining primary productivity in todays oceans1. Yet, their evolutionary history and role in shaping Earths early biosphere remain entirely unexplored. Here, we trace the origins of microbial exoenzymes and reveal their previously unrecognized role in driving planetary oxygenation. Our results show that exoenzymes are more common in microorganisms utilizing high-energy metabolisms, likely reflecting the energetic costs of enzyme biosynthesis and secretion. They are especially advantageous in environments rich in particulate organic matter (POM). A refined carbon cycle model indicates that early Archean oceans offered few such habitats, as low productivity and intense UV radiation rapidly photodegraded POM. However, with a Paleoproterozoic rise of atmospheric oxygen2, increased oxidative weathering boosted marine primary productivity and POM accumulation3, creating conditions favoring exoenzyme evolution. Molecular clock analyses further indicate that alkaline phosphatase, a key phosphorus-releasing exoenzyme, had likely emerged with the permanent rise of oxygen, enabling more efficient phosphorus recycling. We propose that exoenzymes initiated a positive feedback loop: by accelerating nutrient regeneration, they fueled cyanobacterial productivity and oxygen release, which in turn favored greater exoenzyme capacity, reinforcing long-term oxygenation of the planet.

microbiology↗

bioRxiv2023

The role of the AP-1 adaptor complex in outgoing and incoming membrane traffic

The AP-1 adaptor complex is found in all eukaryotes, but it has been implicated in different pathways in different organisms. To look directly at AP-1 function, we generated stably transduced HeLa cells co-expressing tagged AP-1 and various tagged membrane proteins. Live cell imaging showed that AP-1 is recruited onto tubular carriers trafficking from the Golgi apparatus to the plasma membrane, as well as onto transferrin-containing early/recycling endosomes. Analysis of single AP-1 vesicles showed that they are a heterogeneous population, which start to sequester cargo by 30 minutes after exit from the ER. Vesicle capture showed that AP-1 vesicles contain transmembrane proteins found at the TGN and early/recycling endosomes, as well as lysosomal hydrolases, but very little of the anterograde adaptor GGA2. Together, our results support a model in which AP-1 retrieves proteins from post-Golgi compartments back to the TGN, analogous to COPIs role in the early secretory pathway. We propose that this is the function of AP-1 in all eukaryotes. SummaryRobinson et al. investigate AP-1 function using complementary approaches on cells co-expressing tagged AP-1 and cargo proteins. Their results support a model in which AP-1 is recruited onto post-Golgi carriers and early/recycling endosomes, where it retrieves selected proteins back to the TGN.

cell biology↗

bioRxiv2020

Deep learning and alignment of spatially-resolved whole transcriptomes of single cells in the mouse brain with Tangram

Charting a biological atlas of an organ, such as the brain, requires us to spatially-resolve whole transcriptomes of single cells, and to relate such cellular features to the histological and anatomical scales. Single-cell and single-nucleus RNA-Seq (sc/snRNA-seq) can map cells comprehensively5,6, but relating those to their histological and anatomical positions in the context of an organs common coordinate framework remains a major challenge and barrier to the construction of a cell atlas7-10. Conversely, Spatial Transcriptomics allows for in-situ measurements11-13 at the histological level, but at lower spatial resolution and with limited sensitivity. Targeted in situ technologies1-3 solve both issues, but are limited in gene throughput which impedes profiling of the entire transcriptome. Finally, as samples are collected for profiling, their registration to anatomical atlases often require human supervision, which is a major obstacle to build pipelines at scale. Here, we demonstrate spatial mapping of cells, histology, and anatomy in the somatomotor area and the visual area of the healthy adult mouse brain. We devise Tangram, a method that aligns snRNA-seq data to various forms of spatial data collected from the same brain region, including MERFISH1, STARmap2, smFISH3, and Spatial Transcriptomics4 (Visium), as well as histological images and public atlases. Tangram can map any type of sc/snRNA-seq data, including multi-modal data such as SHARE-seq data5, which we used to reveal spatial patterns of chromatin accessibility. We equipped Tangram with a deep learning computer vision pipeline, which allows for automatic identification of anatomical annotations on histological images of mouse brain. By doing so, Tangram reconstructs a genome-wide, anatomically-integrated, spatial map of the visual and somatomotor area with [~]30,000 genes at single-cell resolution, revealing spatial gene expression and chromatin accessibility patterning beyond current limitation of in-situ technologies.

genomics↗