Search for: All records

Abstract The evolutionary transition to multicellularity requires shifting the primary unit of selection from cells to multicellular collectives. How this occurs in aggregative organisms remains poorly understood. Clonal development provides a direct path to multicellular adaptation through genetic identity between cells, but aggregative organisms face a constraint: selection on collective-level traits cannot drive adaptation without positive genetic assortment. We leveraged experimental evolution of flocculatingSaccharomyces cerevisiaeto examine the evolution and role of genetic assortment in multicellular adaptation. After 840 generations of selection for rapid settling, 13 of 19 lineages evolved increased positive assortment relative to their ancestor. However, assortment provided no competitive advantage during settling selection, suggesting it arose as an indirect effect of selection on cell-level traits rather than through direct selection on collective-level properties. Genetic reconstruction experiments and protein structure modeling revealed two distinct pathways to assortment: kin recognition mediated by mutations in theFLO1adhesion gene and generally enhanced cellular adhesion that improved flocculation efficiency independent of partner genotype. The evolution of assortment without immediate adaptive benefit suggests that key innovations enabling multicellular adaptation may arise indirectly through cell-level selection. Our results demonstrate fundamental constraints on aggregative multicellularity and help explain why aggregative lineages have remained simple. 

Oxygen availability is a key factor in the evolution of multicellularity, as larger and more sophisticated organisms often require mechanisms allowing efficient oxygen delivery to their tissues. One such mechanism is the presence of oxygen-binding proteins, such as globins and hemerythrins, which arose in the ancestor of bilaterian animals. Despite their importance, the precise mechanisms by which oxygen-binding proteins influenced the early stages of multicellular evolution under varying environmental oxygen levels are not yet clear. We address this knowledge gap by heterologously expressing the oxygen-binding proteins myoglobin and myohemerythrin in snowflake yeast, a model system of simple, undifferentiated multicellularity. These proteins increased the depth and rate of oxygen diffusion, increasing the fitness of snowflake yeast growing aerobically. Experiments show that, paradoxically, oxygen-binding proteins confer a greater fitness benefit for larger organisms when O₂is least limiting. We show via biophysical modeling that this is because facilitated diffusion is more efficient when oxygen is abundant, transporting a greater quantity of O₂which can be used for metabolism. By alleviating anatomical diffusion limitations to oxygen consumption, the evolution of oxygen-binding proteins in the oxygen-rich Neoproterozoic may have been a key breakthrough enabling the evolution of increasingly large, complex multicellular metazoan lineages. 

Recent advancements in multi-mode Gottesman-Kitaev-Preskill (GKP) codes have shown great promise in enhancing the protection of both discrete and analog quantum information. This broadened range of protection brings opportunities beyond quantum computing to benefit quantum sensing by safeguarding squeezing — the essential resource in many quantum metrology protocols. However, the potential for quantum sensing to benefit quantum error correction has been less explored. In this work, we provide a unique example where techniques from quantum sensing can be applied to improve multi-mode GKP codes. Inspired by distributed quantum sensing, we propose the distributed two-mode squeezing (dtms) GKP codes that offer benefits in error correction with minimal active encoding operations. Indeed, the proposed codes rely on a $single$(active) two-mode squeezing element and an array of beamsplitters that effectively distributes continuous-variable correlations to many GKP ancillae, similar to continuous-variable distributed quantum sensing. Despite this simple construction, the code distance achievable with dtms-GKP qubit codes is comparable to previous results obtained through brute-force numerical search \cite{lin2023closest}. Moreover, these codes enable analog noise suppression beyond that of the best-known two-mode codes \cite{noh2020o2o} without requiring an additional squeezer. We also provide a simple two-stage decoder for the proposed codes, which appears near-optimal for the case of two modes and permits analytical evaluation. 

Rhomboid proteases are ubiquitous intramembrane serine proteases that can cleave transmembrane substrates within lipid bilayers. They exhibit many and diverse functions, such as but not limited to, growth factor signaling, immune and inflammatory response, protein quality control, and parasitic invasion. Human rhomboid protease RHBDL4 has been demonstrated to play a critical role in removing misfolded proteins from the endoplasmic reticulum and is implicated in severe diseases such as various cancers and Alzheimer's disease. Therefore, RHBDL4 is expected to constitute an important therapeutic target for such devastating diseases. Despite its critical role in many biological processes, the enzymatic properties of RHBDL4 remain largely unknown. To enable a comprehensive characterization of RHBDL4's kinetics, catalytic parameters, substrate specificity, and binding modality, we expressed and purified recombinant RHBDL4 and employed it in a Förster resonance energy transfer-based cleavage assay. Until now, kinetic studies have been limited mostly to bacterial rhomboid proteases. Our in vitro platform offers a new method for studying RHBDL4's enzymatic function and substrate preferences. Furthermore, we developed and tested potential inhibitors using our assay and successfully identified peptidyl α-ketoamide inhibitors of RHBDL4 that are highly effective against recombinant RHBDL4. We utilize ensemble docking and molecular dynamics simulations to explore the binding modality of substrate-derived peptides bound to RHBDL4. Our analysis focused on key interactions and dynamic movements within RHBDL4's active site that contributed to binding stability, offering valuable insights for optimizing the nonprime side of RHBDL4 ketoamide inhibitors. In summary, our study offers fundamental insights into RHBDL4's catalytic activities and substrate preferences, laying the foundation for downstream applications such as drug inhibitor screenings and structure-function studies, which will enable the identification of lead drug compounds for RHBDL4. 

Abstract Hybridization and introgression are widespread in nature, with important implications for adaptation and speciation. Since heterogametic hybrids often have lower fitness than homogametic individuals, a phenomenon known as Haldane’s rule, loci inherited strictly through the heterogametic sex rarely introgress. We focus on the Y-chromosomal history of guenons, African primates that hybridized extensively in the past. Although our inferences suggest that Haldane’s rule generally applies, we uncover a Y chromosome introgression event between two species ca. six million years after their initial divergence. Using simulations, we show that selection likely drove the introgressing Y chromosome to fixation from a low initial frequency. We identify non-synonymous substitutions on the novel Y chromosome as candidate targets of selection, and explore meiotic drive as an alternative mechanism. Our results provide a rare example of Y chromosome introgression, showing that the ability to produce fertile heterogametic hybrids likely persisted for six million years in guenons.