Jean Vila

All Publications

• Massively parallel experimental interrogation of natural variants in ancient signaling pathways reveals both purifying selection and local adaptation. bioRxiv : the preprint server for biology Aguilar-Rodríguez, J., Vila, J., Chen, S. A., Razo-Mejia, M., Ghosh, O., Fraser, H. B., Jarosz, D. F., Petrov, D. A. 2024

  Abstract

  The nature of standing genetic variation remains a central debate in population genetics, with differing perspectives on whether common variants are mostly neutral or have functional effects. We address this question by directly mapping the fitness effects of over 9,000 natural variants in the Ras/PKA and TOR/Sch9 pathways-key regulators of cell proliferation in eukaryotes-across four conditions in Saccharomyces cerevisiae. While many variants are neutral in our assay, on the order of 3,500 exhibited significant fitness effects. These non-neutral variants tend to be missense and affect conserved, more densely packed, and less solvent-exposed protein regions. They are also typically younger, occur at lower frequencies, and more often found in heterozygous states, suggesting they are subject to purifying selection. A substantial fraction of non-neutral variants showing strong fitness effects in our experiments, however, is present at high frequencies in the population. These variants show signs of local adaptation as they tend to be found specifically in domesticated strains adapted to human-made environments. Our findings support the view that while common variants are often neutral, a significant proportion have adaptive functional consequences and are driven into the population by local positive selection. This study highlights the potential to explore the functional effects of natural genetic variation on a genome scale with quantitative fitness measurements in the laboratory, bridging the gap between population genetics and functional genomics to understand evolutionary dynamics in the wild.

  View details for DOI 10.1101/2024.10.30.621178

  View details for PubMedID 39553990

  View details for PubMedCentralID PMC11565963

• Global epistasis and the emergence of function in microbial consortia. Cell Diaz-Colunga, J., Skwara, A., Vila, J. C., Bajic, D., Sanchez, A. 2024

  Abstract

  The many functions of microbial communities emerge from a complex web of interactions between organisms and their environment. This poses a significant obstacle to engineering microbial consortia, hindering our ability to harness the potential of microorganisms for biotechnological applications. In this study, we demonstrate that the collective effect of ecological interactions between microbes in a community can be captured by simple statistical models that predict how adding a new species to a community will affect its function. These predictive models mirror the patterns of global epistasis reported in genetics, and they can be quantitatively interpreted in terms of pairwise interactions between community members. Our results illuminate an unexplored path to quantitatively predicting the function of microbial consortia from their composition, paving the way to optimizing desirable community properties and bringing the tasks of predicting biological function at the genetic, organismal, and ecological scales under the same quantitative formalism.

  View details for DOI 10.1016/j.cell.2024.04.016

  View details for PubMedID 38776921

• Competition for shared resources increases dependence on initial population size during coalescence of gut microbial communities. bioRxiv : the preprint server for biology Goldman, D. A., Xue, K. S., Parrott, A. B., Jeeda, R. R., Franzese, L. R., Lopez, J. G., Vila, J. C., Petrov, D. A., Good, B. H., Relman, D. A., Huang, K. C. 2023

  Abstract

  The long-term success of introduced populations depends on their initial size and ability to compete against existing residents, but it remains unclear how these factors collectively shape colonization. Here, we investigate how initial population (propagule) size and resource competition interact during community coalescence by systematically mixing eight pairs of in vitro microbial communities at ratios that vary over six orders of magnitude, and we compare our results to a neutral ecological model. Although the composition of the resulting co-cultures deviated substantially from neutral expectations, each co-culture contained species whose relative abundance depended on propagule size even after ~40 generations of growth. Using a consumer-resource model, we show that this dose-dependent colonization can arise when resident and introduced species have high niche overlap and consume shared resources at similar rates. This model predicts that propagule size will have larger, longer-lasting effects in diverse communities in which niche overlap is higher, and we experimentally confirm that strain isolates show stronger dose dependence when introduced into diverse communities than in pairwise co-culture. This work shows how neutral-like colonization dynamics can emerge from non-neutral resource competition and have lasting effects on the outcomes of community coalescence.

  View details for DOI 10.1101/2023.11.29.569120

  View details for PubMedID 38076867

  View details for PubMedCentralID PMC10705444

• Metabolic similarity and the predictability of microbial community assembly. bioRxiv : the preprint server for biology Vila, J. C., Goldford, J., Estrela, S., Bajic, D., Sanchez-Gorostiaga, A., Damian-Serrano, A., Lu, N., Marsland, R., Rebolleda-Gomez, M., Mehta, P., Sanchez, A. 2023

  Abstract

  When microbial communities form, their composition is shaped by selective pressures imposed by the environment. Can we predict which communities will assemble under different environmental conditions? Here, we hypothesize that quantitative similarities in metabolic traits across metabolically similar environments lead to predictable similarities in community composition. To that end, we measured the growth rate and by-product profile of a library of proteobacterial strains in a large number of single nutrient environments. We found that growth rates and secretion profiles were positively correlated across environments when the supplied substrate was metabolically similar. By analyzing hundreds of in-vitro communities experimentally assembled in an array of different synthetic environments, we then show that metabolically similar substrates select for taxonomically similar communities. These findings lead us to propose and then validate a comparative approach for quantitatively predicting the effects of novel substrates on the composition of complex microbial consortia.

  View details for DOI 10.1101/2023.10.25.564019

  View details for PubMedID 37961608

  View details for PubMedCentralID PMC10634833

• The architecture of metabolic networks constrains the evolution of microbial resource hierarchies. Molecular biology and evolution Takano, S., Vila, J. C., Miyazaki, R., Sanchez, A., Bajic, D. 2023

  Abstract

  Microbial strategies for resource use are an essential determinant of their fitness in complex habitats. When facing environments with multiple nutrients, microbes often use them sequentially according to a preference hierarchy, resulting in well-known patterns of diauxic growth. In theory, the evolutionary diversification of metabolic hierarchies could represent a mechanism supporting coexistence and biodiversity by enabling temporal segregation of niches. Despite this ecologically critical role, the extent to which substrate preference hierarchies can evolve and diversify remains largely unexplored. Here we used genome-scale metabolic modeling to systematically explore the evolution of metabolic hierarchies across a vast space of metabolic network genotypes. We find that only a limited number of metabolic hierarchies can readily evolve, corresponding to the most commonly observed hierarchies in genome-derived models. We further show how the evolution of novel hierarchies is constrained by the architecture of central metabolism, which determines both the propensity to change ranks between pairs of substrates and the effect of specific reactions on hierarchy evolution. Our analysis sheds light on the genetic and mechanistic determinants of microbial metabolic hierarchies, opening new research avenues to understand their evolution, evolvability, and ecology.

  View details for DOI 10.1093/molbev/msad187

  View details for PubMedID 37619982

• Predictability of the community-function landscape in wine yeast ecosystems. Molecular systems biology Ruiz, J., de Celis, M., Diaz-Colunga, J., Vila, J. C., Benitez-Dominguez, B., Vicente, J., Santos, A., Sanchez, A., Belda, I. 2023: e11613

  Abstract

  Predictively linking taxonomic composition and quantitative ecosystem functions is a major aspiration in microbial ecology, which must be resolved if we wish to engineer microbial consortia. Here, we have addressed this open question for an ecological function of major biotechnological relevance: alcoholic fermentation in wine yeast communities. By exhaustively phenotyping an extensive collection of naturally occurring wine yeast strains, we find that most ecologically and industrially relevant traits exhibit phylogenetic signal, allowing functional traits in wine yeast communities to be predicted from taxonomy. Furthermore, we demonstrate that the quantitative contributions of individual wine yeast strains to the function of complex communities followed simple quantitative rules. These regularities can be integrated to quantitatively predict the function of newly assembled consortia. Besides addressing theoretical questions in functional ecology, our results and methodologies can provide a blueprint for rationally managing microbial processes of biotechnological relevance.

  View details for DOI 10.15252/msb.202311613

  View details for PubMedID 37548146

• Emergent coexistence in multispecies microbial communities SCIENCE Chang, C., Bajic, D., Vila, J. C., Estrela, S., Sanchez, A. 2023; 381 (6655): 343-348

  Abstract

  Understanding the mechanisms that maintain microbial biodiversity is a critical aspiration in ecology. Past work on microbial coexistence has largely focused on species pairs, but it is unclear whether pairwise coexistence in isolation is required for coexistence in a multispecies community. To address this question, we conducted hundreds of pairwise competition experiments among the stably coexisting members of 12 different enrichment communities in vitro. To determine the outcomes of these experiments, we developed an automated image analysis pipeline to quantify species abundances. We found that competitive exclusion was the most common outcome, and it was strongly hierarchical and transitive. Because many species that coexist within a stable multispecies community fail to coexist in pairwise co-culture under identical conditions, we concluded that multispecies coexistence is an emergent phenomenon. This work highlights the importance of community context for understanding the origins of coexistence in complex ecosystems.

  View details for DOI 10.1126/science.adg0727

  View details for Web of Science ID 001046763100034

  View details for PubMedID 37471535