Step-wise evolution of azole resistance through copy number variation followed byKSR1loss of heterozygosity inCandida albicans DOI Creative Commons
Pétra Vande Zande, Cécile Gautier,

Nora Kawar

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 5, 2024

Abstract Antimicrobial drug resistance poses a global health threat, requiring deeper understanding of the evolutionary processes that lead to its emergence in pathogens. Complex dynamics involve multiple mutations can result cooperative or competitive (clonal interference) effects. Candida albicans , major fungal pathogen, displays high rates copy number variation (CNV) and loss heterozygosity (LOH). CNV LOH events large numbers genes could synergize during adaptation. Understanding contributions antifungal adaptation is challenging, especially context whole-population genome sequencing. Here, we document sequential evolution fluconazole tolerance then C. isolate involving an initial on chromosome 4, followed by R involves KSR1 . Similar KSR1, which encodes reductase involved sphingolipid biosynthesis, were also detected independently evolved resistant isolates. We dissect specific codons affect tolerance. The combination 4 results >500-fold increase azole resistance, illustrating compelling example rapid, yet step-wise, interplay between evolution.

Язык: Английский

Genome duplication in a long-term multicellularity evolution experiment. DOI
Kai Tong, Sayantan Datta,

Vivian Cheng

и другие.

PubMed, Год журнала: 2025, Номер unknown

Опубликована: Март 5, 2025

Язык: Английский

Процитировано

1

The role of gene copy number variation in antimicrobial resistance in human fungal pathogens DOI Creative Commons

Alan R. Jay,

David Jordan, Aleeza C. Gerstein

и другие.

npj Antimicrobials and Resistance, Год журнала: 2025, Номер 3(1)

Опубликована: Янв. 6, 2025

Faced with the burden of increasing resistance to antifungals in many fungal pathogens and constant emergence new drug-resistant strains, it is essential assess importance various mechanisms. Fungi have relatively plastic genomes can tolerate genomic copy number variation (CNV) caused by aneuploidy gene amplification or deletion. In cases, these changes lead adaptation stressful conditions, including those antifungal drugs. Here, we specifically examine contribution CNVs resistance. We undertook a thorough literature search, collecting reports CNV, classifying examples CNV-conferred into four main find that human pathogens, there little evidence plays major role compared other types mutations. discuss why might be underestimating their approaches being used study them.

Язык: Английский

Процитировано

1

Fungal Stress Responses and the Importance of GPCRs DOI Creative Commons

Daniela Lara-Martínez,

Fabiola Estefanía Tristán-Flores, Juan Antonio Cervantes‐Montelongo

и другие.

Journal of Fungi, Год журнала: 2025, Номер 11(3), С. 213 - 213

Опубликована: Март 11, 2025

G-protein-coupled receptors (GPCRs) play a crucial role in the gene regulation of processes related to response different types stress fungi. These act as sensors extracellular signals and transmit information interior cell through G-proteins. In presence specific stresses, GPCRs activate signaling cascades that culminate activation transcription factors, which regulate expression genes associated with response, including those induced by changes environmental pH. GPCR-mediated allows fungi adapt adverse conditions such osmotic, thermal, oxidative, or nutritional stress, well fluctuations This review focuses on understanding how modulate their advancing our knowledge physiology adaptability these microorganisms changing environment.

Язык: Английский

Процитировано

1

Step-wise evolution of azole resistance through copy number variation followed by KSR1 loss of heterozygosity in Candida albicans DOI Creative Commons
Pétra Vande Zande, Cécile Gautier,

Nora Kawar

и другие.

PLoS Pathogens, Год журнала: 2024, Номер 20(8), С. e1012497 - e1012497

Опубликована: Авг. 30, 2024

Antimicrobial drug resistance poses a global health threat, requiring deeper understanding of the evolutionary processes that lead to its emergence in pathogens. Complex dynamics involve multiple mutations can result cooperative or competitive (clonal interference) effects. Candida albicans, major fungal pathogen, displays high rates copy number variation (CNV) and loss heterozygosity (LOH). CNV LOH events large numbers genes could synergize during adaptation. Understanding contributions antifungal adaptation is challenging, especially context whole-population genome sequencing. Here, we document sequential evolution fluconazole tolerance then C. albicans isolate involving an initial on chromosome 4, followed by R involves KSR1. Similar KSR1, which encodes reductase sphingolipid biosynthesis pathway, were also detected independently evolved resistant isolates. We dissect specific KSR1 codons affect tolerance. The combination 4 results >500-fold decrease azole susceptibility relative progenitor, illustrating compelling example rapid, yet step-wise, interplay between evolution.

Язык: Английский

Процитировано

5

Single-cell detection of copy number changes reveals dynamic mechanisms of adaptation to antifungals in Candida albicans DOI
Xin Zhou, Audrey L. Hilk, Norma V. Solis

и другие.

Nature Microbiology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 3, 2024

Язык: Английский

Процитировано

5

Puzzles, challenges, and information reservoir of SARS-CoV-2 quasispecies DOI
Esteban Domingo, Brenda Martínez‐González, Carlos García‐Crespo

и другие.

Journal of Virology, Год журнала: 2023, Номер 97(12)

Опубликована: Ноя. 21, 2023

Upon the emergence of SARS-CoV-2 in human population, it was conjectured that for this coronavirus dynamic intra-host heterogeneity typical RNA viruses would be toned down. Nothing sort is observed. Here we review main observations on complexity and diverse composition mutant spectra sampled from infected patients, within framework quasispecies dynamics. The analyses suggest information provided by myriads genomic sequences individuals may have a predictive value acquire epidemiological relevance. Possibilities to reconcile presence broad large genome with its encoding 3' 5' exonuclease proofreading-repair activity are considered. Indeterminations behavior individual viral genomes provide benefit survival ensemble. We propose concept falls domain "stochastic thinking," notion applies also cellular processes, as means biological systems face unexpected needs.

Язык: Английский

Процитировано

10

Comparative modeling reveals the molecular determinants of aneuploidy fitness cost in a wild yeast model DOI Creative Commons
Julie Rojas,

James Hose,

H Auguste Dutcher

и другие.

Cell Genomics, Год журнала: 2024, Номер 4(10), С. 100656 - 100656

Опубликована: Сен. 23, 2024

Язык: Английский

Процитировано

4

Polyploidy-mediated resilience in hepatic aging: molecular mechanisms and functional implication DOI Creative Commons
Majeed M. A. Ali

Egyptian Liver Journal, Год журнала: 2024, Номер 14(1)

Опубликована: Ноя. 12, 2024

Abstract Background Polyploidization, a process where cells acquire additional chromosome sets, is unique characteristic of hepatocytes. This has been increasingly recognized as an adaptive mechanism for maintaining liver function during aging, period characterized by cellular senescence, DNA damage, and metabolic dysregulation. Purpose review explores the molecular mechanisms underlying hepatocyte polyploidization its potential role in promoting resilience against aging-related decline function. We assess how polyploid hepatocytes contribute to genomic stability, stress resistance, adaptation, highlighting their relevance aging. Main body Hepatocyte occurs through such cytokinesis failure endoreplication, leading binuclear or mononuclear cells. Polyploid exhibit enhanced repair capacity, which helps mitigate accumulation age-related damage. The increased gene dosage facilitates better responses, particularly oxidative genotoxic insults. Metabolic adaptations, including xenobiotic metabolism lipid regulation, further support liver’s ability maintain homeostasis Additionally, demonstrate altered epigenetic landscapes proteostasis mechanisms, contributing improved reduced susceptibility senescence. These adaptations collectively enhance structural challenges. Conclusion represents critical protective that safeguard instability, dysfunction, stress. Understanding pathways driving could pave way novel therapeutic strategies combat disorders health span. Graphical

Язык: Английский

Процитировано

4

Comparative modeling reveals the molecular determinants of aneuploidy fitness cost in a wild yeast model DOI Creative Commons
Julie Rojas,

James Hose,

H Auguste Dutcher

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 13, 2024

Although implicated as deleterious in many organisms, aneuploidy can underlie rapid phenotypic evolution. However, will only be maintained if the benefit outweighs cost, which remains incompletely understood. To quantify this cost and molecular determinants behind it, we generated a panel of chromosome duplications

Язык: Английский

Процитировано

3

Intraspecific diploidization of a halophyte root fungus drives heterosis DOI Creative Commons
Zhong‐Feng Li,

Zhiyong Zhu,

Kun Qian

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июль 12, 2024

Abstract How organisms respond to environmental stress is a key topic in evolutionary biology. This study focused on the genomic evolution of Laburnicola rhizohalophila , dark-septate endophytic fungus from roots halophyte. Chromosome-level assemblies were generated five representative isolates structured subpopulations. The data revealed significant plasticity resulting chromosomal polymorphisms created by fusion and fission events, known as dysploidy. Analyses features, phylogenomics, macrosynteny have provided clear evidence for origin intraspecific diploid-like hybrids. Notably, one diploid phenotype stood out an outlier exhibited conditional fitness advantage when exposed range abiotic stresses compared with its parents. By comparing gene expression patterns each hybrid parent triad under four growth conditions, mechanisms underlying vigor corroborated through analysis transgressively upregulated genes enriched membrane glycerolipid biosynthesis transmembrane transporter activity. In vitro assays suggested increased integrity lipid accumulation, well decreased malondialdehyde production optimal salt conditions (0.3 M NaCl) hybrid. These attributes been implicated salinity tolerance. supports notion that hybridization-induced genome doubling leads emergence phenotypic innovations extremophilic endophyte.

Язык: Английский

Процитировано

3