Biology subjects

Alonso-del-Real, J.

Publications and source records attributed to Alonso-del-Real, J..

3 recordsLinked to original sources

bioRxiv2025

Complete genomes reveal the full extent of Mycobacterium tuberculosis complex diversity across evolutionary scales

Advances in short-read sequencing have enhanced our understanding of Mycobacterium tuberculosis complex (MTBC), but fail to capture its complete genomic diversity. We applied long-read sequencing to 216 isolates from the Valencia Region (Spain) and generated high-quality, complete genomes, revealing detailed insights into MTBC evolution across timescales. Complete genome comparisons increased the estimated evolutionary rate by 1.5-fold, resulting in a median of 312 (-1 to 792) additional SNPs per pairwise comparison. Multiple diversity hotspots were identified, mostly in the pe/ppe genes and driven by gene conversion. However, most PE/PPE epitopes were hyperconserved, with notable exceptions involving vaccine candidates. Incorporating previously undetected SNPs and indels improved resolution in transmission analyses. Furthermore, patient-specific reference mapping validates only 5-10% of within-host diversity detected by standard pipelines, indicating substantial overestimation in previous studies. These findings expand our view of MTBC diversity and have important implications for understanding host-pathogen interactions, epidemiology, and transmission dynamics.

genomics↗

bioRxiv2024

Identification of a crucial INO2 allele for enhancing ethanol resistance in an industrial fermentation strain of Saccharomyces cerevisiae

Ethanol toxicity is a major challenge for S. cerevisiae during fermentation, affecting its growth and influencing the process. This study investigated the molecular mechanisms of ethanol tolerance using transcriptomic analysis of three S. cerevisiae strains with varying ethanol resistance. We identified distinct responses in membrane lipid synthesis genes, particularly in ergosterol biosynthesis, regulated by the Ino2p transcription factor. A variant of Ino2p with V263I and H86R amino acid replacements was exclusive to ethanol-tolerant strains. CRISPR-Cas9-mediated point mutations in the INO2 gene of the highly tolerant strain AJ4 resulted in decreased ethanol tolerance. Our findings demonstrate the crucial role of Ino2p in ethanol tolerance through regulation of lipid synthesis and membrane composition, highlighting the complex interplay of trans elements in strain-specific ethanol resistance IMPORTANCEThis study provides critical insights into the molecular basis of ethanol tolerance in S. cerevisiae, a key trait for improving industrial fermentation processes. By identifying specific genetic variants in the Ino2p transcription factor and their impact on ethanol resistance, we reveal potential targets for enhancing yeast strain performance in high-ethanol environments. Our findings not only contribute to the fundamental understanding of stress response mechanisms in yeast but also offer practical implications for strain engineering in the biotechnology and beverage industries. The unexpected magnitude of the Ino2p variants effect on ethanol tolerance underscores the importance of considering strain-specific genetic backgrounds in metabolic engineering strategies

microbiology↗

bioRxiv2023

Divergence in the Saccharomyces species' heat shock response is indicative of their thermal tolerance

The Saccharomyces species have diverged in their thermal growth profile. Both S. cerevisiae and S. paradoxus grow at temperatures well above the maximum growth temperature of S. kudriavzevii and S. uvarum, but grow more poorly at lower temperatures. In response to thermal shifts, organisms activate a stress response that includes heat shock proteins involved in protein homeostasis and acquisition of thermal tolerance. To determine whether Saccharomyces species have diverged in their response to temperature we measured changes in gene expression in response to a 12{degrees}C increase or decrease in temperature for four Saccharomyces species and their six pairwise hybrids. To ensure coverage of subtelomeric gene families we sequenced, assembled and annotated a complete S. uvarum genome. All the strains exhibited a stronger response to heat than cold treatment. In response to heat, the cryophilic species showed a stronger response than the thermophilic species. The hybrids showed a mixture of parental stress responses depending on the time point. After the initial response, hybrids with a thermophilic parent were more similar to S. cerevisiae and S. paradoxus, and the S. cerevisiae x S. paradoxus hybrid showed the weakest heat shock response. Within the hybrids a small subset of temperature responsive genes showed species specific responses but most were also hybrid specific. Our results show that divergence in the heat shock response is indicative of a strains thermal tolerance, suggesting that cellular factors that signal heat stress or resolve heat induced changes are relevant to thermal divergence in the Saccharomyces species.

evolutionary biology↗