Biology subjects

Loegler, V.

Publications and source records attributed to Loegler, V..

5 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

Graph-based pangenome analysis uncovers structural and functional impacts of allopolyploidization events

The emergence of graph pangenomes has significantly advanced the study of structural variants (SVs) across diverse species. However, the impact of complex polyploidization events, particularly allopolyploidy, on SV landscapes remains poorly explored. Brettanomyces bruxellensis, a yeast species shaped by multiple allopolyploidization events, offers a compelling model due to its well-characterized genomic and phenotypic diversity. Here, we integrated subgenome-resolved assemblies with population-scale genomic and transcriptomic datasets to characterize SVs distribution and their functional impact at the species level. Leveraging a constructed reference graph pangenome, we identified sequences that are unique to each subgenome, and detected 212,177 SVs across 1,060 sequenced isolates. Allopolyploid genomes harbored significantly more SVs (320 on average) than diploid genomes (116 on average), reflecting the extensive impact of hybridization on the genome architecture. A subset of SVs originating from ancestral divergence between subgenomes (hybridization-associated SVs) formed distinct hotspots of structural diversity. Furthermore, functional association analysis revealed that 27.5% of SVs exert local regulatory effects on gene expression. Interestingly, hybridization-associated structural variants disproportionately affect gene expression, with a greater proportion of associated variants and a significantly larger effect size compared to other SVs. Overall, these findings underscore the role of allopolyploidization in driving both structural and functional genomic diversification. Our study also highlights the value of graph-based approaches in dissecting complex genome evolution.

genomics↗

bioRxiv2024

Overview of the Saccharomyces cerevisiae population structure through the lens of 3,034 genomes

With the rise of high-throughput sequencing technologies, a holistic view of genetic variation within populations - through population genomics studies - appears feasible, although it remains an ongoing effort. Genetic variation arises from a diverse range of evolutionary forces, with mutation and recombination being key drivers in shaping genomes. Studying genetic variation within a population represents a crucial first step in understanding the relationship between genotype and phenotype and the evolutionary history of species. In this context, the budding yeast Saccharomyces cerevisiae has been at the forefront of population genomic studies. In addition, it has a complex history that involves adaptation to a wide range of wild and human-related ecological niches. Although to date more than three thousand diverse isolates have been sequenced, there is currently a lack of a resource bringing together sequencing data and associated metadata for all sequenced isolates. To perform a comprehensive analysis of the population structure of S. cerevisiae, we collected genome sequencing data from 3,034 natural isolates and processed the data uniformly. We determined ploidy levels, identified single nucleotide polymorphisms (SNPs), small insertion-deletions (InDels), copy number variations (CNVs), and aneuploidies across the population, creating a publicly accessible resource for the yeast research community. Interestingly, we showed that this population captures [~]93% of the species diversity. Using neighbor-joining and Bayesian methods, we redefined the populations, revealing clustering patterns primarily based on ecological origin. This work represents a valuable resource for the community and efforts have been made to make it evolvable and integrable to future yeast population studies.

genomics↗

bioRxiv2023

Species-wide quantitative transcriptomes and proteomes reveal distinct genetic control of gene expression variation in yeast

Gene expression varies between individuals and corresponds to a key step linking genotypes to phenotypes. However, our knowledge regarding the species-wide genetic control of protein abundance, including its dependency on transcript levels, is very limited. Here, we have determined quantitative proteomes of a large population of 942 diverse natural Saccharomyces cerevisiae yeast isolates. We found that mRNA and protein abundances are weakly correlated at the population gene level. While the protein co-expression network recapitulates major biological functions, differential expression patterns reveal proteomic signatures related to specific populations. Comprehensive genetic association analyses highlight that genetic variants associated with variation in protein (pQTL) and transcript (eQTL) levels poorly overlap (3.6%). Our results demonstrate that transcriptome and proteome are governed by distinct genetic bases, likely explained by protein turnover. It also highlights the importance of integrating these different levels of gene expression to better understand the genotype-phenotype relationship. HighlightsO_LIAt the level of individual genes, the abundance of transcripts and proteins is weakly correlated within a species ({rho} = 0.165). C_LIO_LIWhile the proteome is not imprinted by population structure, co-expression patterns recapitulate the cellular functional landscape C_LIO_LIWild populations exhibit a higher abundance of respiration-related proteins compared to domesticated populations C_LIO_LILoci that influence protein abundance differ from those that impact transcript levels, likely because of protein turnover C_LI

systems biology↗

bioRxiv2023

Pan-transcriptome reveals a large accessory genome contribution to gene expression variation in yeast

Gene expression is an essential step in the translation of genotypes into phenotypes. However, little is known about the transcriptome architecture and the underlying genetic effects at a species-level. Here, we generated and analyzed the pan-transcriptome of [~]1,000 yeast natural isolates across 4,977 core and 1,468 accessory genes. We found that the accessory genome is an underappreciated driver of the transcriptome divergence. Global gene expression patterns combined with population structure show that the heritable expression variation mainly lies within subpopulation-specific signatures, for which the accessory genes are overrepresented. Genome-wide association analyses consistently highlight that the accessory genes are associated with proportionally more variants with larger effect sizes, illustrating the critical role of the accessory genome on the transcriptional landscape within and between populations.

genomics↗