Biology subjects

Barre, B. P.

Publications and source records attributed to Barre, B. P..

9 recordsLinked to original sources

bioRxiv2026

A reproductive hierarchy controls mating fates among sibling yeast gametes

Mating strategies shape inbreeding, gene flow and genetic diversity, yet their outcomes remain challenging to quantify. In Saccharomyces, population-genomic models predict mating predominantly between sibling meiotic products, with rare selfing and outcrossing. Here we developed an integrated framework combining multicolor flow cytometry, time-resolved imaging and mathematical modelling to directly quantify mating across scales. Bulk measurements revealed coexisting strategies whose frequencies vary with density, genotype and environment. A minimal stochastic model uses these population-level patterns to infer probabilistic hierarchies among mating modes, which single-tetrad analyses independently support. These reveal divergent and interdependent reproductive trajectories among sibling gametes, with one pair typically mating first and reshaping opportunities for the others. Temporal heterogeneity in germination and mating further diversifies reproductive outcomes and shapes compatibility, as experimental synchronization overcomes temporal reproductive barriers, enabling hybridization. Together, reproductive strategy emerges from heterogeneous gamete fates, raising the possibility that sibling diversification constitutes reproductive bet-hedging.

genetics↗

bioRxiv2025

Assessing the molecular and phenotypic contribution of a horizontally acquired region to yeast adaptation

Horizontal Gene Transfer (HGT) is the movement of genetic material across species. In Saccharomyces cerevisiae, a DNA segment known as Region B was acquired horizontally from a distant yeast species. This region ([~]17 Kb) encodes 5 genes and is present in the genomes of yeast strains from different phylogenetic clades, with its contribution to yeast niche-specific adaptation remaining unclear. In this work, the genomic structure of Region B was analyzed in yeast strains from the ScRAP (Saccharomyces cerevisiae Reference Assembly Panel) collection, identifying 10 variants that maintain a circular continuity. To assess the role of Region B in yeast adaptation, we performed a high-throughput phenotyping of the ScRAP collection under different growth conditions, identifying that Region B is potentially associated with higher tolerance to oxidative stress. Then, we selected a single yeast strain from the ScRAP collection for characterization of the transcriptional activity of each gene within Region B using a fluorescent reporter. The results revealed that gene expression depends on the hosts genetic background and transcription factors encoded within Region B. To identify the genetic determinants involved in Region B expression within different genetic backgrounds, three expression Quantitative Trait Loci (eQTLs) were mapped and validated. Finally, by performing Region B deletion, we determine the contribution of this region to different fermentative phenotypes, including fermentation rate and amino acid consumption. Altogether, our results suggest a complex regulatory interaction between the horizontally acquired genes and the host genome that contributes to yeast adaptation under fermentation conditions.

molecular biology↗

bioRxiv2025

The adaptive molecular landscape of reprogrammed telomeric sequences

Telomeric sequences vary across the tree of life and intimately co-evolve with telomere-binding protein complexes. However, the molecular mechanisms allowing organisms to adapt to new telomeric sequences are difficult to gauge from extant species. Here, we reprogrammed multiple yeast lines to human-like telomeric repeats to unveil their molecular and fitness response to novel telomeres. Initially, the exchange of telomere sequences resulted in genome instability, proteome remodelling and severe fitness decline. However, adaptive evolution experiments selected for repeated mutations that drove adaptation to the humanized telomeres. These consisted of the recurrent amplification of the telomere-binding protein TBF1, by complex aneuploidies, or in repeated mutations that attenuate the DNA damage response. Overall, our results outline a response that defines the adaptive molecular landscape to novel telomeric sequences.

evolutionary biology↗

bioRxiv2024

Predicting the natural yeast phenotypic landscape with machine learning

Most organisms traits result from the complex interplay of many genetic and environmental factors, making their prediction from genotypes difficult. Here, we used machine learning models to explore genotype-phenotype connections for 223 life history traits measured across 1011 genome-sequenced Saccharomyces cerevisiae strains. Firstly, we used genome-wide association studies to connect genetic variants with the phenotypes. Next, we benchmarked an automated machine learning pipeline that includes preprocessing, feature selection, and hyperparameters optimization in combination with multiple linear and complex machine learning methods. We determined gradient boosting machines as best performing in 65% of predictions and pangenome as best predictor, suggesting a considerable contribution of the accessory genome in controlling phenotypes. The accuracy broadly varied among the phenotypes (r = 0.2-0.9), consistent with varying levels of complexity, with stress resistance being easier to predict compared to growth across carbon and nitrogen nutrients. While no specific genomic features could be linked to the predictions for most phenotypes, machine learning identifies high-impact variants with established relationships to phenotypes despite being rare in the population. Near-perfect accuracies (r>0.95) were achieved when other phenomics data were used to aid predictions, suggesting shared useful information can be conveyed across phenotypes. Overall, our study underscores the power of machine learning to interpret the functional outcome of genetic variants.

genetics↗

bioRxiv2022

Epigenetic profiling and incidence of disrupted development point to gastrulation as aging ground zero in Xenopus laevis

Recent studies suggest the existence of a natural rejuvenation event during early embryonic development of mice, followed by epigenetic aging. Here, by profiling embryonic DNA methylation in the African clawed frog, Xenopus laevis, we found that the epigenetic entropy basepoint maps to the gastrulation stage of embryogenesis and corresponds to a rapid increase in embryo transcript abundance. We further developed a frog aging clock, revealing that this species epigenetically ages. Application of this clock to developmental stages identified a decrease in epigenetic age during early embryogenesis, with the minimal age reached around gastrulation. By examining individual developmental trajectories of 6,457 embryos, we found that this stage is also accompanied by a higher incidence of disrupted development. Taken together, our data point to gastrulation as a critical stage for aging and natural rejuvenation, characterized by the lowest epigenetic age, increased mortality, nadir of DNA methylation entropy and rapid increase in embryo transcript abundance, defining aging ground zero as the basepoint where rejuvenation ends and the aging process begins.

genetics↗

bioRxiv2022

Telomeres are shorter in wild Saccharomyces cerevisiae isolates than in domesticated ones

Telomeres are ribonucleoproteins that cap chromosome-ends and their DNA length is controlled by counteracting elongation and shortening processes. The budding yeast Saccharomyces cerevisiae has been a leading model to study telomere DNA length control and dynamics. Its telomeric DNA is maintained at a length that slightly varies between laboratory strains, but little is known about its variation at the species level. The recent publication of the genomes of over 1000 S. cerevisiae strains enabled us to explore telomere DNA length variation at an unprecedented scale. Here, we developed a bioinformatic pipeline (YeaISTY) to estimate telomere DNA length from whole-genome-sequences and applied it to the sequenced 1011 S. cerevisiae collection. Our results revealed broad natural telomere DNA length variation among the isolates. Notably, telomere DNA length is shorter in those derived from wild rather than domesticated environments. Wild isolates are enriched in loss-of-function mutations in genes known to regulate telomere DNA length and the return of domesticated yeasts to a wild habitat coincides with shorter telomeres. Moreover, telomere DNA length variation is associated with mitochondrial metabolism, and this association is driven by wild strains. Overall, these findings suggest that budding yeasts telomere DNA length regulation might be shaped by ecological life-styles.

genomics↗

bioRxiv2020

Aborting meiosis overcomes hybrid sterility

Hybrids between species or diverged lineages contain fundamentally novel genetic combinations but an impaired meiosis often makes them evolutionary dead ends. Here, we explored to what extent and how an aborted meiosis followed by a return-to-growth (RTG) promotes recombination across a panel of 20 yeast diploid backgrounds with different genomic structures and levels of sterility. Genome analyses of 284 clones revealed that RTG promoted recombination and generated extensive regions of loss-of-heterozygosity in sterile hybrids with either a defective meiosis or a heavily rearranged karyotype, whereas RTG recombination was reduced by high sequence divergence between parental subgenomes. The RTG recombination preferentially occurred in regions with local sequence homology and in meiotic recombination hotspots. The loss-of-heterozygosity had a profound impact on sexual and asexual fitness, and enabled genetic mapping of phenotypic differences in sterile lineages where linkage or association analyses failed. We propose that RTG gives sterile hybrids access to a natural route for genome recombination and adaptation. One sentence summaryAborting meiosis followed by a return to mitotic growth promotes evolution by genome wide-recombination in sterile yeast hybrids.

genetics↗

bioRxiv2020

Domestication reprogrammed the budding yeast life cycle

Domestication of plants and animals is the foundation for feeding the world population. We report that domestication of the model yeast S. cerevisiae reprogrammed its life cycle entirely. We tracked growth, gamete formation and cell survival across many environments for nearly 1000 genome sequenced isolates and found a remarkable dichotomy between domesticated and wild yeasts. Wild yeasts near uniformly trigger meiosis and sporulate when encountering nutrient depletions, whereas domestication relaxed selection on sexual reproduction and favoured survival as quiescent cells. Domestication also systematically enhanced fermentative over respiratory traits while decreasing stress tolerance. We show that this yeast domestication syndrome was driven by aneuploidies and gene function losses that emerged independently in multiple domesticated lineages during the species recent evolutionary history. We found domestication to be the most dramatic event in budding yeast evolution, raising questions on how much domestication has distorted our understanding of this key model species.

evolutionary biology↗

bioRxiv2019

Intragenic repeat expansions control yeast chronological aging

Aging varies among individuals due to both genetics and environment but the underlying molecular mechanisms remain largely unknown. Using a highly recombined Saccharomyces cerevisiae population, we found 30 distinct Quantitative Trait Loci (QTLs) that control chronological life span (CLS) in calorie rich and calorie restricted environments, and under rapamycin exposure. Calorie restriction and rapamycin extended life span in virtually all genotypes, but through different genetic variants. We tracked the two major QTLs to massive expansions of intragenic tandem repeats in the cell wall glycoproteins FLO11 and HPF1, which caused a dramatic life span shortening. Life span impairment by N-terminal HPF1 repeat expansion was partially buffered by rapamycin but not by calorie restriction. The HPF1 repeat expansion shifted yeast cells from a sedentary to a buoyant state, thereby increasing their exposure to surrounding oxygen. The higher oxygenation perturbed methionine, lipid, and purine metabolism, which likely explains the life span shortening. We conclude that fast evolving intragenic repeat expansions can fundamentally change the relationship between cells and their environment with profound effects on cellular life style and longevity.

genomics↗