Biology subjects

Jerison, E. R.

Publications and source records attributed to Jerison, E. R..

7 recordsLinked to original sources

bioRxiv2025

Parallel but distinct adaptive routes in the budding and fission yeasts after 10,000 generations of experimental evolution

Quantitative genetics approaches designed to understand the evolution of traits have helped improve our understanding of the genetic basis of adaptation. However, they often overlook crucial aspects of adaptation, including the long-term temporal evolutionary dynamics, the predictability of evolutionary outcomes, the influence of past evolution on future evolutionary trajectories (contingency), and the diversity of molecular mechanisms underlying adaptation. Experimental evolution has been a useful tool for answering these questions, but extracting fundamental principles and predictive features of evolutionary outcomes from these datasets remains challenging due to the large number of covariates and confounding effects, such as differences in experimental setup, species lifestyle, gene content, and evolution rate. Here, we sought to circumvent these challenges by comparing distant yeast species that share several evolutionary features but differ mainly in evolutionary history and genome architecture, i.e. Saccharomyces cerevisiae and Schizosaccharomyces pombe. Thus, we evolved 10 populations of the fission yeast for 10,000 generations in the same conditions as a pre-existing budding yeast dataset (i.e. high-sugar media and hypoxic conditions), allowing us to observe repeatable evolutionary outcomes within species but diverse molecular mechanisms and targets of adaptation across species. The most frequent adapting route in these conditions involved upregulating fermentation genes and downregulating the glycolysis gene pyk1, which has not previously been observed in S. cerevisiae evolved populations or in wild Kluyveromyces lactis, but similar evolutionary paths have been observed in Schizosaccharomyces japonicus and in clinically relevant populations, such as some cancer cells. This suggests that parallelism is pervasive in the tree of life and that mechanisms of adaptation can be shared among closely related or distant species. Despite similar gene content and identical environments, recurrent adaptation across S. pombe populations involved different genes than in S. cerevisiae and was mostly detectable at the transcriptomic level. This suggests that trans-regulatory effects may play an important role in adaptation on short evolutionary timescales and that differences in evolutionary outcomes between these species may be attributed to contingency.

evolutionary biology↗

bioRxiv2025

Spatially-structured inflammatory response in the presence of a uniform stimulus

Inflammatory responses occur within the complex spatial context of tissues and organs, and many questions remain about how tissue structure and cellular communication shape their spatiotemporal dynamics. Here, we use a multiplexed RNA in situ hybridization approach, together with analytical tools, to study inflammatory gene expression in the larval zebrafish tailfin in response to a bath of lipopolysaccharide (LPS). We use this model system to address whether spatial structure emerges in the tissue response even absent the spatial variation introduced by a pathogen. We find that epithelial cells in the tailfin express several pro-inflammatory genes, and that across these genes, the uniform stimulus triggers a spatially non-uniform response. We use a graph-based spectral decomposition method to analyze its structure, and find that long modes dominate, creating zones of activation. Overall, these zones account for a majority of the variation in gene expression. Our results show that epithelial cells are important producers of pro-inflammatory effector molecules in this system, and that tissue induces spatial correlations even absent a structured input.

systems biology↗

bioRxiv2023

Reference-Free Germline Immunoglobulin Allele Discovery from B CellReceptor Sequencing Data

Antibodies, or immunoglobulins, are a diverse set of molecules that play a critical role in adaptive immunity. They are generated in a process which begins with the recombination of germline V, D, and J gene segment alleles, and refined by hypermutation of these germline sequences upon antigen exposure. Antibody repertoire analysis often requires the knowledge of the germline V, D, and J alleles to detect hypermutations and understand the phylogenetic relationships of related B cells. However, germline immunoglobulin alleles are remarkably diverse and incompletely annotated, making it necessary to construct personalized databases for every individual. Though several approaches for the detection of germline immunoglobulin variants exist, they often rely on refining existing databases using simplifying assumptions about the relationships of germline alleles in a given organism, or about the form of evolutionary process that shapes antibody repertoires. Here, we present grmlin, an alternative computational approach to detecting germline alleles. Our approach exploits two empirical properties of B cell repertoires: the abundance of germline sequences in antibody repertoires and the enormous diversity of antibody sequence space, to detect germline alleles from B cell receptor sequencing data without reliance on a reference database. As such, it is in principle applicable to non-model organisms. We validate this approach by detecting the germline alleles of 11 pairs of twins and show that it achieves equivalent sensitivity and better specificity than previous methods.

immunology↗

bioRxiv2020

Phenotypic and molecular evolution across 10,000 generations in laboratory budding yeast populations

Laboratory experimental evolution provides a window into the details of the evolutionary process. To investigate the consequences of long-term adaptation, we evolved 205 S. cerevisiae populations (124 haploid and 81 diploid) for [~]10,000 generations in three environments. We measured the dynamics of fitness changes over time, finding repeatable patterns of declining adaptability. Sequencing revealed that this phenotypic adaptation is coupled with a steady accumulation of mutations, widespread genetic parallelism, and historical contingency. In contrast to long-term evolution in E. coli, we do not observe long-term coexistence or populations with highly elevated mutation rates. We find that evolution in diploid populations involves both fixation of heterozygous mutations and frequent loss-of-heterozygosity events. Together, these results help distinguish aspects of evolutionary dynamics that are likely to be general features of adaptation across many systems from those that are specific to individual organisms and environmental conditions.

evolutionary biology↗

bioRxiv2019

A T cell behavioral manifold couples speed and turning to create heterogeneity in vivo

T cells in vivo migrate primarily via undirected random walks, but it remains unresolved how these random walks generate an efficient search. Here, we use light sheet microscopy of T cells in the larval zebrafish as a model system to study motility across large populations of cells over hours in their native context. We show that cell-to-cell variability is amplified by a correlation between speed and directional persistence, generating a characteristic cell behavioral manifold that is preserved under a perturbation to cell speeds, and seen in Mouse T cells and Dictyostelium. These results suggest that there is a single variable underlying ameboid cell motility that jointly controls speed and turning. This coupling explains behavioral heterogeneity in diverse systems and allows cells to access a broad range of length scales.

biophysics↗

bioRxiv2019

Chance and Necessity in the Pleiotropic Consequences of Adaptation for Budding Yeast

Mutations that a population accumulates during evolution in one ("home") environment may cause fitness gains or losses in other conditions. Such pleiotropic fitness effects determine the evolutionary fate of the population in variable environments and can lead to ecological specialization. It is unclear how the pleiotropic outcomes of evolution are shaped by the intrinsic randomness of the evolutionary process and by the deterministic variation in selection pressures across environments. To address this question, we evolved 20 replicate populations of the yeast Saccharomyces cerevisiae in 11 laboratory environments and measured their fitness across multiple other conditions. We found that evolution in all home environments led to a diversity of patterns of pleiotropic fitness gains and losses, driven by multiple types of mutations. Approximately 60% percent of this variation are explained by clones home environment and the most common parallel genetic changes, while about 40% are attributed to the stochastic accumulation of mutations whose pleiotropic effects are unpredictable. On average, populations specialized to their home environment, but generalists also evolved in almost all conditions. Our results suggest that the mutations accumulating in a home environment incur a variety of pleiotropic effects, from costs to benefits, with different probabilities. Therefore, whether a population evolves towards a specialist or a generalist phenotype is heavily influenced by chance.

evolutionary biology↗

bioRxiv2017

Genetic Variation In Adaptability And Pleiotropy In Budding Yeast

Evolution can favor organisms that are more adaptable, provided that genetic variation in adaptability exists. Here, we quantify this variation among 230 offspring of a cross between diverged yeast strains. We measure the adaptability of each offspring genotype, defined as its average rate of adaptation in a specific environmental condition, and analyze the heritability, predictability, and genetic basis of this trait. We find that initial genotype strongly affects adaptability and can alter the genetic basis of future evolution. Initial genotype also affects the pleiotropic consequences of adaptation for fitness in a different environment. This genetic variation in adaptability and pleiotropy is largely determined by initial fitness, according to a rule of declining adaptability with increasing initial fitness, but several individual QTLs also have a significant idiosyncratic role. Our results demonstrate that both adaptability and pleiotropy are complex traits, with extensive heritable differences arising from naturally occurring variation.

evolutionary biology↗