Liu, P.-J. | bioRxiv Science

bioRxiv2025

A Dynamic Framework for Context Dependent Microbial Assembly: Validation of the Domain-Specific Stochastic Deterministic Integration Model (DSSDI)

Microbial community assembly is governed by the interplay of stochastic and deterministic processes. However, most existing frameworks treat microbial communities as taxonomically homogeneous entities, overlooking the phylogenetic divergence and ecological distinctiveness of major microbial domains. Here, we present a new conceptual model--Domain-Specific Stochastic-Deterministic Integration (DSSDI)--that explicitly incorporates domain-level asymmetries, cross-domain interactions, and functional buffering into the community assembly process. Using 16S rRNA sequencing data from seasonal intertidal microbial communities, we tested four hypotheses derived from the DSSDI framework. Our results revealed that bacterial and archaeal communities differ in their stochastic-deterministic assembly patterns, spatial-temporal responses, network modularity, and functional robustness. Cross-domain cooperation emerged as a stabilizing factor, promoting metabolic complementarity and buffering against taxonomic turnover. This study introduces and validates the DSSDI framework as the first domain-explicit model of microbial community assembly, establishing a clear conceptual foundation and claiming priority for future theoretical and empirical developments in this field.

microbiology↗

bioRxiv2021

Steroid-resistant nephrotic syndrome associated MYO1E mutations have differential effects on myosin 1e localization, dynamics, and activity

Myo1e is a non-muscle motor protein enriched in the podocyte foot processes. Mutations in MYO1E are associated with steroid-resistant nephrotic syndrome (SRNS). Here, we set out to differentiate between the pathogenic and neutral MYO1E variants identified in SRNS patients by exome sequencing. Based on protein sequence conservation and structural predictions, two mutations in the motor domain, T119I and D388H, were selected for this study. EGFP-tagged Myo1e constructs were delivered into the Myo1e-KO podocytes via adenoviral infection to analyze Myo1e protein stability, Myo1e localization, and clathrin-dependent endocytosis, which is known to involve Myo1e activity. Furthermore, truncated Myo1e constructs were expressed using the baculoviral expression system and used to measure Myo1e ATPase and motor activity in vitro. Both mutants were expressed as full-length proteins in the Myo1e-KO podocytes. However, unlike wild-type (WT) Myo1e, the T119I variant was not enriched at the cell junctions or clathrin-coated vesicles (CCVs) in podocytes. In contrast, the D388H variant localization was similar to the WT. Surprisingly, the dissociation of the D388H variant from cell-cell junctions and CCVs was decreased, suggesting that this mutation also affects Myo1e activity. The ATPase activity and the ability to translocate actin filaments were drastically reduced for the D388H mutant, supporting the findings from cell-based experiments. The experimental pipeline developed in this study allowed us to determine that the T119I and D388H mutations appear to be pathogenic and gain additional knowledge in the Myo1e role in podocytes. This workflow can be applied to the future characterization of novel MYO1E variants associated with SRNS.

cell biology↗