Biology subjects

Garin, M.

Publications and source records attributed to Garin, M..

4 recordsLinked to original sources

bioRxiv2025

Population-scale chemical response revealed by a barcoded yeast collection

Natural genetic variation shapes how microbial populations adapt to environmental and chemical challenges, but scalable approaches to map genotype-phenotype relationships across diverse genetic backgrounds remain limited. Here, we developed a systematically barcoded collection of 520 Saccharomyces cerevisiae natural isolates that captures the ecological, geographical and genetic diversity of the species. Using pooled barcode sequencing, we profiled fitness responses to over 600 bioactive and natural compounds, revealing broader and more polarized bioactivity than the standard yeast gene-deletion collection. Fitness-based clustering defined six major compound groups with reproducible, population-structured sensitivity patterns. Genome-wide association analysis identified significant genetic variants across 107 compounds, linking natural polymorphisms to chemical responses and involving genes in genome maintenance, ribosome biogenesis, vesicular trafficking and stress tolerance. Together, our barcoded natural population provides a scalable framework for chemical-genetic screening, enabling systematic dissection of how genetic diversity shapes microbial fitness and adaptation.

evolutionary biology↗

bioRxiv2025

An empirical long-term competition among natural yeast isolates reveals that short-term fitness largely but not entirely predicts long-term outcomes

The fitness of an organism determines its likelihood of succeeding in short-term competition, but many other factors can influence its long-term success. In this study, we investigate the relative contribution of initial fitness to a strain's long-term success in a naturally diverse population. Specifically, we compete a pool of 282 genetically barcoded S. cerevisiae isolates for up to 720 generations in six distinct environments. We find that the strains that remain at detectable frequency until the end of the competition uniformly come from the initially fittest top 5% of strains, rendering initial fitness a strong predictor of long-term success. However, small fitness differences among the top strains matter little for their long-term evolutionary fate. Indeed, we often see heterogeneity in the competition outcomes across replicates, suggesting that stochastic, large-effect adaptive mutations overwrite small differences in the initial fitness of the highest fitness strains. In addition, our results hint that evolvability differences might result in certain strains consistently over- or underperforming in the competition. We further demonstrate that the "finalists" of our competition accumulate a diverse spectrum of de novo genetic changes: single nucleotide mutations, indels, whole chromosome losses and amplifications, and widespread losses of heterozygosity that occasionally span hundreds of kilobases. Taken together, we show that for a pool of natural strains, high initial fitness is necessary, though not sufficient, to succeed long-term, and that adaptive evolution can drive unexpected outcomes in a long-term competition in a novel environment.

evolutionary biology↗

bioRxiv2024

Recurrent loss of crossover interference punctuates the recombination landscape across yeast species

Meiotic recombination is essential for the accurate chromosome segregation and the generation of genetic diversity through crossover and gene conversion events. Although this process has been studied extensively in a few selected model species, understanding how its properties vary across species remains limited. In this context, we first characterized the meiotic recombination landscape and properties of the Kluyveromyces lactis budding yeast. We then conducted a comprehensive analysis of 28,897 recombination events spanning 567 meioses in five budding yeast species including Saccharomyces cerevisiae, Saccharomyces paradoxus, Lachancea kluyveri, Lachancea waltii and K. lactis. We observed variations in the recombination landscapes and properties across these species. The Saccharomyces yeasts displayed higher recombination rates compared to the non-Saccharomyces yeasts. In addition, bona fide crossover interference and associated crossover homeostasis were found in the Saccharomyces species only. The evolutionarily conserved ZMM pathway, essential for generating interference-dependent crossovers, has undergone multiple losses throughout evolution, suggesting variations in the regulation of crossover formation. Finally, recombination hotspots, although highly conserved within the Saccharomyces yeasts are not conserved beyond the Saccharomyces genus. Overall, these results highlight great variability and evolution in the recombination landscape between species.

genomics↗

bioRxiv2021

Population-level survey of loss-of-function mutations revealed that background dependent fitness genes are rare and functionally related in yeast

In natural populations, the same mutation can lead to different phenotypic outcomes due to the genetic variation that exists among individuals. Such genetic background effects are commonly observed, including in the context of many human diseases. However, systematic characterization of these effects at the species level is still lacking to date. Here, we sought to comprehensively survey background-dependent traits associated with gene loss-of-function (LoF) mutations in 39 natural isolates of Saccharomyces cerevisiae using a transposon saturation strategy. By analyzing the modeled fitness variability of a total of 4,469 genes, we found that 15% of them, when impacted by a LoF mutation, exhibited a significant gain- or loss-of-fitness phenotype in certain natural isolates compared to the reference strain S288C. Out of these 632 genetic background-dependent fitness genes identified, a total of 2/3 show a continuous variation across the population while 1/3 are specific to a single genetic background. Genes related to mitochondrial function are significantly overrepresented in the set of genes showing a continuous variation and display a potential functional rewiring with other genes involved in transcription and chromatin remodeling as well as in nuclear-cytoplasmic transport. Such rewiring effects are likely modulated by both the genetic background and the environment. While background-specific cases are rare and span diverse cellular processes, they can be functionally related at the individual level. All background-dependent fitness genes tend to have an intermediate connectivity in the global genetic interaction network and have shown relaxed selection pressure at the population level, highlighting their potential evolutionary characteristics.

genetics↗