Biology subjects

Kahn, P. C.

Publications and source records attributed to Kahn, P. C..

5 recordsLinked to original sources

bioRxiv2026

Evolutionary rescue in toxic combinations of metal is dependent on metal interactions

Populations facing abrupt environmental change may avoid extinction through evolutionary rescue, in which beneficial mutations allow individuals to survive and reproduce under otherwise lethal conditions. However, theory on evolutionary rescue has largely focused on single stressors, leaving open how interactions among simultaneous stressors shape adaptation. In particular, synergistic interactions, which amplify toxicity, and antagonistic interactions, which reduce it, may impose distinct selective pressures and lead to different fitness outcomes. To investigate this, we experimentally evolved Saccharomyces cerevisiae under lethal combinations of six metals (Cd, Co, Cu, Mn, Ni, and Zn), obtaining rescued lines in eight of the fifteen pairwise combinations. We then measured the fitness of evolved lines in the original metal combination, each component metal individually, and the ancestral environment. Adaptation differed systematically with metal interactions: lines evolved in antagonistic combinations generally gained fitness in the individual metals as well as in the combination, whereas lines evolved in synergistic combinations tended to show more specialized adaptation, with fitness benefits concentrated in the combination and reduced fitness in the component metals. No rescue was observed in combinations whose toxicity was consistent with concentration addition, although differences in the precise toxicity of experimental treatments may have influenced rescue outcomes. These findings demonstrate that interactions among simultaneous stressors can shape not only the likelihood of evolutionary rescue but also the breadth of its fitness benefits, highlighting the importance of accounting for stressor interactions when investigating evolutionary responses to environmental change.

evolutionary biology↗

bioRxiv2025

Quantifying the effect of metal interactions on growth rate in Saccharomyces cerevisiae

Environmental stressors often co-occur, yet their combined effects on organisms remain poorly understood. As multifactorial anthropogenic changes intensify and alter environmental selection pressures, our understanding of stressor interactions is becoming increasingly important. However, established methods for characterizing the effects of stressor interactions can involve considerable experimental and computational labour. Here, we investigate how pairwise combinations of six divalent metal ions (Cd2+, Co2+, Cu2+, Mn2+, Ni2+, and Zn2+) affect the growth of Saccharomyces cerevisiae, using a high-throughput assay to generate concentration-response surfaces for all 15 combinations. We introduce{delta} , an easily calculable metric that quantifies the toxicity of a mixture relative to the toxicities of its individual components, and compare it to an established metric for synergism/antagonism, a, determined by calculating deviation from a null model of additivity, i.e., "concentration addition". Yeast growth rates reveal that metal mixture toxicity varies widely from the additive expectation with the effect of the combination ranging from greatly enhanced toxicity to greatly attenuated toxicity. Combinations with copper were more toxic than expected, and combinations with manganese or nickel were less. These trends correspond to known redox activities and metal-binding properties, pointing to possible mechanistic underpinnings rooted in oxidative stress and metal cofactor displacement. Furthermore, we find that a correlates with overlap in known metal resistance genes and similarity in redox potential, offering predictive insight into effects of metal interactions. While a provides a model-based measure of synergism or antagonism,{delta} serves as an intuitive, concentration-robust descriptor of ecological impact. Together, these metrics highlight the complexity of metal-metal interactions and the importance of accounting for nonadditive effects in ecotoxicological assessments. This framework provides a basis for evaluating mixture toxicity across diverse taxa and stressor types, with implications for both evolutionary biology and environmental risk assessment.

ecology↗

bioRxiv2023

Experimental evolution of multicellularity via cuboidal cell packing in fission yeast

The evolution of multicellularity represents a major transition in lifes history, enabling the rise of complex organisms. Multicellular groups can evolve through multiple developmental modes, but a common step is the formation of permanent cell-cell attachments after division. The characteristics of the multicellular morphology which emerges has profound consequences for the subsequent evolution of a nascent multicellular lineage, but little prior work has examined these dynamics directly. Here we examine a widespread yet understudied emergent multicellular morphology: cuboidal packing. Extinct and extant multicellular organisms across the tree of life have evolved to form groups in which spherical cells divide but remain attached, forming approximately cubic subunits. To experimentally investigate the evolution of cuboidal cell packing, we used settling selection to favor the evolution of simple multicellularity in unicellular, spherical Schizosaccharomyces pombe yeast. Multicellular clusters with cuboidal organization rapidly evolved, displacing the unicellular ancestor. These clusters displayed key hallmarks of an evolutionary transition in individuality: groups possess an emergent life cycle driven by physical fracture, group size is heritable, and they respond to group-level selection via multicellular adaptation. In 2/5 lineages, group formation was driven by mutations in the ACE2 gene, preventing daughter cell separation after division. Remarkably, ACE2 mutations also underlie the transition to multicellularity in Saccharomyces cerevisiae and C. galabrata, lineages last shared a common ancestor >300 million years ago. Our results provide insight into the evolution of cuboidal cell packing, an understudied multicellular morphology, and highlights the deeply convergent potential for a transition to multicellular individuality within fungi.

evolutionary biology↗

bioRxiv2021

De novo evolution of macroscopic multicellularity

While early multicellular lineages necessarily started out as relatively simple groups of cells, little is known about how they became Darwinian entities capable of open-ended multicellular adaptation1,2. To explore this, we initiated the Multicellularity Long Term Evolution Experiment (MuLTEE), selecting for larger group size in the snowflake yeast (Saccharomyces cerevisiae) model system. Given the historical importance of oxygen limitation3, our ongoing experiment consists of three metabolic treatments4: anaerobic, obligately aerobic, and mixotrophic yeast. After 600 rounds of selection, snowflake yeast in the anaerobic treatment evolved to be macroscopic, becoming ~2{middle dot}104 times larger (~mm scale) and ~104-fold more biophysically tough, while retaining a clonal multicellular life cycle. They accomplished this through sustained biophysical adaptation, evolving increasingly elongate cells that initially reduced the strain of cellular packing, then facilitated branch entanglements that enabled groups of cells to stay together even after many cellular bonds fracture. In contrast, snowflake yeast competing for low oxygen remained microscopic, evolving to be just ~6-fold larger, underscoring the critical role of oxygen levels in the evolution of multicellular size. Taken together, this work provides unique insight into an ongoing evolutionary transition in individuality, showing how simple groups of cells overcome fundamental biophysical limitations via gradual, yet sustained, multicellular adaptation.

evolutionary biology↗

bioRxiv2019

Interaction of NPC2 protein with Lysobisphosphatidic Acid is required for normal endolysosomal cholesterol trafficking

Unesterified cholesterol accumulation in the late endosomal/lysosomal (LE/LY) compartment is the cellular hallmark of Niemann-Pick C (NPC) disease, caused by defects in the genes encoding NPC1 or NPC2. We previously reported the dramatic stimulation of NPC2 cholesterol transport rates by the LE/LY phospholipid lysobisphosphatidic acid (LBPA) and in these studies sought to determine their functional relationship in normal LE/LY cholesterol egress. Here we demonstrate that NPC2 interacts directly with LBPA and identify the NPC2 hydrophobic knob domain as the site of interaction. Using its precursor phosphatidylglycerol (PG), we show that PG-induced LBPA enrichment results in clearance of accumulated cholesterol from NPC1-deficient cells but is ineffective in cells lacking functional NPC2. Together these studies reveal a heretofore unknown aspect of intracellular cholesterol trafficking, in which NPC2 and LBPA function together in an obligate step of sterol egress from the LE/LY compartment, which appears to be independent of NPC1.

biochemistry↗