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PubMed2026

Population-level genomic surveillance of human norovirus using wastewater-based whole-genome sequencing.

Wastewater-based surveillance has garnered increasing attention as a valuable approach for capturing community-level infection dynamics that are often difficult to detect through clinical reporting systems alone. In this study, we analyzed human norovirus genotype distributions and whole-genome-level variations in wastewater samples collected in Gwangju, Korea. These results were interpreted in conjunction with a documented foodborne outbreak to evaluate the epidemiological relevance of wastewater-based monitoring. Human norovirus concentrations were quantified using TaqMan Array Card-based RT-qPCR, and whole-genome next-generation sequencing (NGS) was performed to obtain viral read counts and reads per kilobase per million filtered reads values. Overall, strong correlations were observed between RT-qPCR-based concentrations and NGS-derived metrics. Genotype dynamics varied among wastewater treatment plants, reflecting differences in catchment size and local population characteristics. In particular, the relative abundance of GII.17[P17] increased during epidemiological week 50, temporally coinciding with a documented local foodborne outbreak. Variant analysis revealed that wastewater samples exhibited mixed nucleotide patterns, with multiple alleles coexisting at varying relative frequencies rather than fixed substitutions. Notably, some nonsynonymous variants detected in clinical samples were also observed in wastewater samples collected surrounding the outbreak period. Together, these findings demonstrate that wastewater-based whole-genome surveillance can capture both genotype-level shifts and nucleotide-level dynamics at the population scale, highlighting its potential as a complementary tool for monitoring community-level norovirus circulation and outbreak-associated genotype dynamics.IMPORTANCEWastewater-based surveillance is increasingly recognized as a promising approach for capturing community-level infection dynamics that are often missed by clinical surveillance. In this study, we applied whole-genome sequencing to wastewater samples collected in Gwangju, South Korea, to comprehensively characterize human norovirus genotype distributions and genetic variation. Distinct genotype patterns were observed across wastewater treatment plants, reflecting differences in catchment population size and local characteristics. Notably, an increase in the GII.17[P17] genotype detected in wastewater coincided with a foodborne outbreak investigated in Gwangju, demonstrating the potential of wastewater surveillance to reflect ongoing community transmission and emerging outbreak-associated genotypes. In addition, wastewater samples contained diverse and coexisting genetic variants, capturing population-level viral diversity and evolutionary dynamics that are not readily detected through clinical surveillance alone. These findings highlight the value of wastewater-based whole-genome surveillance for monitoring community-level viral circulation and support its integration as a complementary strategy to existing clinical surveillance systems.

genotype dynamics↗

PubMed2026

Genome-wide identification and functional analysis of the BES1-like (VfBES1) gene family in Vernicia fordii reveals its role in floral development.

BACKGROUND: Vernicia fordii Hemsl (also known as Tung tree), an significant commercial oil-producing tree species, is a monoecious and diclinous species with male and female flowers on the same inflorescence; however, the molecular mechanisms governing its floral sex determination remain elusive, particularly the genetic basis underlying the skewed female-to-male flower ratio and the evolutionary dynamics of sex-related gene families, which severely restrict targeted breeding for yield enhancement. In the model plant Arabidopsis, the BRI1 EMS SUPPRESSOR 1 (BES1) transcription factor family plays a crucial role in Brassinosteroid (BR) signaling and reproductive development. However, its function remains largely unexplored in woody perennials. RESULTS: In this study, we introduce the genome-wide identification and functional characterization of the BES1-like (VfBES1) gene family in the Tung tree for the first time. Integrative multi-omics approaches reveal seven VfBES1 genes that are clustered into three phylogenetically distinct clades, each characterized by clade-specific motifs and structural simplicity. Segmental duplication events (VfBES1-1/VfBES1-5 and VfBES1-4/VfBES1-7) and promoter cis-element enrichment (hormone-responsive and abiotic stress-related motifs) highlight evolutionary innovation and functional diversification. Spatiotemporal expression profiling reveals VfBES1 genes' tissue- and stage-specific roles. VfBES1-1 predominantly expresses in female flowers and fruits, suggesting its possible roles in late-stage sex maintenance or ovule and fruit development. VfBES1-2 and VfBES1-6 exhibit male flower-specific and early floral developmental activation, respectively. Nuclear-localized VfBES1-6 displays co-expression with VfMYB35-1 gene, which is a regulator of male structure degeneration. CONCLUSIONS: Findings in this study shed light on the regulatory roles of VfBES1 genes in the floral development of the Tung tree, providing a reference for its precision breeding to enhance flowering synchrony and seed productivity. This study also provides a comparative framework for understanding the functional diversity of BES1-like genes in non-model woody plants.

Flowers↗

PubMed2026

Plasmids as persistent genetic reservoirs of bacterial defense systems in wastewater treatment.

BACKGROUND: Bacterial antiphage defense systems play essential roles in microbial ecology, yet their dynamics within urban wastewater systems (UWS) remain poorly characterized. RESULTS: In this study, we performed comprehensive metagenomic and plasmidome analyses on 78 wastewater samples collected during two seasons and four sampling points across UWS from three European countries. We observed a significant reduction in the abundance, diversity, and mobility potential of defense systems during biological treatment. However, these reductions were not directly correlated with changes in microbial abundance. Defense systems were significantly enriched on plasmids, particularly conjugative plasmids, where their gene density was approximately twice as high as on chromosomes and remained relatively stable across compartments. In contrast to chromosomal defense systems, plasmid-borne systems exhibited more frequent co-localization with a wide range of mobile genetic elements (MGEs)-associated genes, thereby facilitating multilayered dissemination networks. Furthermore, we detected a strong correlation between phage abundance and host defense system profiles, indicating ongoing phage-host co-evolutionary dynamics in these environments. CONCLUSIONS: In summary, our results demonstrate that UWS reduce the abundance and diversity of bacterial defense system genes. However, plasmid-associated defense systems can persist through shared mobile genetic reservoirs. These findings underscore the critical role of plasmids in bacterial immunity and provide new insights into defense system dynamics within urban wastewater environments.

Plasmids↗

PubMed2025

SARS-CoV-2 genomic diversity and within-host evolution in individuals with persistent infection in the UK: an observational, longitudinal, population-based surveillance study.

BACKGROUND: Persistent SARS-CoV-2 infections in hospitalised immunocompromised individuals are known to facilitate accelerated within-host viral evolution, potentially contributing to the emergence of highly divergent variants. However, little is known about the evolutionary dynamics and transmission risks of persistent infections in the general population. We aimed to characterise the within-host evolution of SARS-CoV-2 during persistent infections identified through a large community surveillance study. METHODS: We used data from the Office for National Statistics COVID-19 Infection Survey (ONS-CIS), a large-scale, longitudinal, population-based surveillance study conducted in the UK from April, 2020, to March, 2023. For this analysis, we focused on infections with high viral load (cycle threshold ≤30) and available genome sequences, from seven major SARS-CoV-2 lineages (alpha, delta, BA.1, BA.2, BA.4, BA.5, and XBB). ONS-CIS participants were randomly selected from the general population and tested regularly by RT-PCR, regardless of symptoms. We defined persistent infections as those with sustained or rebounding high viral RNA titres for 26 days or longer. We examined associated host characteristics and used raw sequence data to identify de novo mutations and estimate within-host synonymous and non-synonymous evolutionary rates across the SARS-CoV-2 genome. FINDINGS: Between Nov 2, 2020, and March 21, 2023, we identified 576 persistent infections with at least two sequences, including 11 alpha, 106 delta, 102 BA.1, 204 BA.2, 16 BA.4, 133 BA.5, and 4 XBB. Persistent infections were more common in males than females (p<0·0001) and individuals older than 60 years (p=0·0027). The median within-host genome-wide evolutionary rate was 7·9 × 10-4 substitutions per site per year (IQR 7·0-9·0 × 10-4), with high inter-individual variability driven largely by non-synonymous mutations, particularly in the N-terminal and receptor-binding domains of the spike protein. Longer infection duration was associated with higher evolutionary rates, while no associations were found with age, sex, vaccination status, previous infection, or virus lineage. We found no clear evidence of transmission beyond the first month of infection in any of the 84 persistent infections lasting 56 days or longer. In total, we identified 379 recurrent mutations, including many with known or predicted negative fitness effects and low prevalence at the population level, as well as de novo reversions to the Wuhan-Hu-1 reference sequence, which were likely under positive selection within those individuals. INTERPRETATION: This study highlights the heterogeneous nature of within-host SARS-CoV-2 evolution in individuals with persistent infection in the community. Notably, a small subset of persistent infections with high viral loads underwent accelerated viral evolution or recurrently acquired hallmark mutations found in novel variants. In addition, onward transmission from a persistent infection during the later stages of infection is likely to be rare. These insights have important implications for prioritising genomic surveillance and managing patients with persistent infections. FUNDING: Department of Health and Social Care.

Humans↗

PubMed2026

Genomic distribution characteristics and interspecific differences of microsatellite landscapes in Felidae.

BACKGROUND: Microsatellites within genomes play crucial roles in regulating gene expression, DNA replication, and chromosomal structure and function. Analyzing the composition and distribution patterns of microsatellites in closely related species not only reveals their evolutionary dynamics and adaptive mechanisms but also provides essential technical support for applications in genetic breeding, species conservation, and disease research. As one of the world's most captivating animal groups, the landscape patterns of microsatellites across feline genomes remain to be systematically characterized. RESULTS: This study utilized high-quality genomic data to conduct a systematic comparative analysis of microsatellite landscape distribution patterns across the genomes of 13 felid species. The findings revealed that microsatellite abundance and distribution exhibit species-specific characteristics, with a non-random genomic distribution and a negative correlation between microsatellite abundance and repeat length. The predominant distribution pattern followed the sequence: single > double > quadruple > triple > quintuple > sextuple nucleotide repeats. Microsatellite abundance peaked in intergenic regions, whereas trinucleotide repeats were more prevalent within exons. Coding regions showed a marked preference for trinucleotide and hexanucleotide repeats. Enrichment analysis of GO and KEGG pathways indicated that coding sequences containing microsatellites were primarily involved in transcription and translation processes. CONCLUSIONS: Our study elucidates the distribution patterns and characteristics of microsatellites across diverse feline species, providing significant insights into their evolutionary mechanisms and functional roles. Furthermore, these findings establish a valuable reference and foundational dataset for the future development of high-quality, species-specific microsatellite markers in felids.

Animals↗

PubMed2026

Identification and characterization of non-canonical azole antifungal resistance pathways in Aspergillus fumigatus.

UNLABELLED: Human fungal infections, especially those caused by Aspergillus fumigatus, pose a significant global health threat, particularly in immunocompromised individuals. Azole antifungals are the primary treatment for this pathogen; however, the prevalence of azole-resistant A. fumigatus strains is steadily increasing. Mutations in cyp51A, which encodes an enzyme involved in ergosterol biosynthesis and the molecular target of the azoles, are well established to confer resistance in this fungal species. However, additional mechanisms governing resistance to this antifungal class remain understudied and poorly characterized, despite growing recognition of their importance in clinical resistance. In this study, we investigated the genetic basis of azole resistance in A. fumigatus isolates from clinical settings worldwide, with a particular focus on mechanisms independent of cyp51A (non-canonical). Using a combination of genomic and functional approaches, including whole-genome sequencing and transcriptomic analysis, we identified novel genetic variants and characterized population structure, advancing our understanding of the genetic diversity and evolutionary dynamics of resistance in A. fumigatus. By expanding our understanding of the complex genetic and molecular factors underlying azole resistance in this important human fungal pathogen, this research is poised to inform the development of novel antifungal strategies and contribute to global efforts to combat fungal infections. IMPORTANCE: Azole antifungals are the frontline therapy for infections caused by the opportunistic mold Aspergillus fumigatus, yet resistance to these drugs is rapidly increasing worldwide. Most studies have focused on mutations in cyp51A, the canonical target of azoles; however, a growing proportion of resistant clinical isolates lack these mutations, indicating that alternative resistance mechanisms are emerging. Here, we integrate population genomics, transcriptomics, and functional analyses across a global collection of isolates to define the architecture of cyp51-independent (non-canonical) azole resistance. We show that this resistance phenotype is strongly associated with a distinct population lineage and is driven by a highly polygenic network of metabolic, mitochondrial, and regulatory adaptations rather than single target site mutations. These isolates exhibit extensive transcriptional rewiring and metabolic remodeling under azole stress, suggesting distinct survival strategies beyond canonical resistance. Our findings reveal that azole resistance in A. fumigatus can evolve through diverse evolutionary routes and emphasize the need to monitor and therapeutically target non-canonical pathways that may increasingly contribute to antifungal treatment failure.

Aspergillus fumigatus↗

PubMed2026

Flavonoid biosynthesis mediated by GmF3Hs contributes to drought tolerance in soybean.

Flavonoids are central to abiotic stress responses, yet the specific signaling roles and evolutionary dynamics of flavonoid biosynthetic intermediates in crop drought adaptation remain elusive. Here, we demonstrate that dihydrokaempferol (DHK) and dihydroquercetin (DHQ), specific intermediate products of the soybean flavanone 3-hydroxylases GmF3H1/2, function as potent signaling molecules that mitigate drought stress. Exogenous DHK/DHQ promoted abscisic acid-dependent stomatal closure and enhanced drought tolerance across diverse dicot species, including soybean and tobacco, highlighting a broadly conserved stress-mitigating signaling mechanism. CRISPR/Cas9-generated gmf3hs double mutants exhibited severe drought hypersensitivity due to compromised redox homeostasis and defective stomatal regulation, which could be specifically rescued by DHK/DHQ application. Furthermore, the loss of GmF3H triggered a distinct reproductive trade-off under stress, leading to increased pod initiation but severe filling defects. Multiomics network analysis revealed extensive rewiring of broader stress-responsive pathways and identified upstream transcription factors, among which GmPHL11 directly binds to and activates the GmF3H1 promoter; overexpression of GmPHL11 promoted DHK accumulation and enhanced drought stress tolerance in soybean hairy roots. Finally, population genomic analyses demonstrated that the GmF3H1H1 haplotype, which confers superior enzymatic activity and robust root growth under drought stress, might have undergone positive selection during soybean domestication. Collectively, our findings redefine the role of GmF3H-derived specific intermediates as potent signaling molecules, providing comprehensive mechanistic and evolutionary insights into flavonoid-mediated drought resilience, developmental trade-offs, and molecular breeding in crops.

Drought Resistance↗

PubMed2026

Genome-wide cyclin gene evolution in Arabidopsis and Brassica reveals polyploidization-driven duplication and flowering-time associations.

Cyclin genes are plant cell cycle regulators that play essential roles in growth, development, and reproduction. However, the evolutionary dynamics and genomic organization of cyclin genes across the Brassicaceae family remain poorly understood, particularly in the context of allotetraploid genome evolution. Here, we investigated the diversity, expansion mechanisms, and potential functional diversification of cyclin genes across ten Brassicaceae genomes, including four Arabidopsis and six Brassica species. A total of 1087 cyclin genes representing 23 cyclin types were identified. Comparative genomic analyses revealed that cyclin gene expansion was strongly influenced by polyploidization in Brassica species, with 1845 duplication events involving 1063 genes. Whole-genome duplication was the predominant mechanism driving expansion, while both inter- and intra-genomic duplications contributed to gene retention in tetraploid Brassica species, with the highest duplication frequency observed in Brassica juncea. Across genomes, 120 physical gene clusters were identified, including homogeneous and heterogeneous types. Ortholog analysis between progenitor and allotetraploid species identified 852 orthologous pairs involving 366 genes, indicating extensive conservation following allotetraploid formation. Phylogenetic analysis resolved cyclins into three major clades, while expression-based clustering in Brassica napus grouped genes into four major clusters, suggesting functional diversification. Integration of pan-genomic and flowering-time QTL analyses further identified two cyclin genes, Bna21cycA2 and Bna113cycD4, which contain amino acid polymorphisms and represent putative candidate variations potentially associated with flowering-time variation across multiple genomes. These findings provide new insights into the evolutionary expansion, retention, and potential functional divergence of cyclin genes in Brassicaceae and highlight candidate loci for future functional studies and crop improvement.

Evolution, Molecular↗

PubMed2026

Pangenome of Streptomyces sampsonii and Relatives Highlights Horizontal Gene Transfer and Secondary Metabolism in Environmental Adaptation and Ecological Significance.

Streptomyces sampsonii is a promising biocontrol bacterium, but its genomic basis of adaptation and secondary metabolism remains unclear. Here, we present a chromosome-level genome assembly of S. sampsonii (7.20 Mb, 6015 protein-coding genes) and perform comparative analyses with 95 related Streptomyces species. Phylogenomic and synteny analyses revealed its closest relationship with S. albidoflavus, while extensive structural variations distinguished more distant lineages. Pangenome analysis uncovered 84,178 gene clusters, with pan_shell and pan_cloud genes predominantly enriched in xenobiotic biodegradation, metabolism, and antibiotic biosynthesis, highlighting their roles in ecological adaptation and biocontrol potential. Biosynthetic gene cluster (BGC) analysis identified numerous NRPS, PKS, and terpene pathways, many of which belong to pan_shell and pan_cloud regions, suggesting dynamic evolutionary origins. We further detected 66,260 horizontally transferred (HGT) genes, including 438 in BGCs, underscoring HGT as a major driver of metabolic innovation. Together, these findings provide novel insights into the genomic diversity, adaptive capacity, and secondary metabolic potential of S. sampsonii and its close relatives.

BGCs↗

PubMed1987

Gradients for the evolution of bimatrix games.

The evolutionary dynamics of bimatrix games is studied for rescaled partnership games and zero sum games. The former case leads to gradient systems. The selection equations for sexual and asexual reproduction of genotypes corresponding to mixed strategies are analysed. As examples, the origin of anisogamy and cyclic chases for predator-prey coevolution are studied.

Animals↗

PubMed1991

The Adh genomic region of Drosophila ambigua: evolutionary trends in different species.

The study of individual genes is essential to a comprehensive understanding of genome evolution. The wealth of information on alcohol dehydrogenase (Adh) in Drosophila makes this gene particularly suitable for such analysis. We have characterized more than 4 kb of the genomic Adh region in Drosophila ambigua and compared this region to Drosophila mauritiana and Drosophila pseudoobscura. The presence of two genes, Adh and 3'ORF (open reading frame), has been confirmed and some of their essential features have been inferred from primary structural analysis. Inter- and intraspecific comparisons have led us to support that both genes may have diverged from an ancient precursor. They appear to be evolving independently, and show a species-specific pattern. The Adh in the obscura group species lacks amino acids three and four when compared to the species of the melanogaster group and has accumulated most of its amino acid replacements in the third exon. Neither characteristic is observed when any other group species are compared, which suggests that these may be particular features of the evolution of the obscura group. The 3'ORF is highly conserved among the three species analyzed, although variability in the length of the third exon and the nucleotide substitution rate, which is much higher than in Adh, are worth noting. According to our data, both mutation/fixation rates and the distribution of mutations vary over time, which makes it difficult to predict the evolutionary dynamics of specific genome regions.

Alcohol Dehydrogenase↗

PubMed1987

Tempo and mode of sequence evolution in mitochondrial DNA of Hawaiian Drosophila.

Sequence comparisons were made for up to 667 bp of DNA cloned from 14 kinds of Hawaiian Drosophila and five other dipteran species. These sequences include parts of the genes for NADH dehydrogenase (subunits 1, 2, and 5) and rRNA (from the large ribosomal subunit). Because the times of divergence among these species are known approximately, the sequence comparisons give insight into the evolutionary dynamics of this molecule. Transitions account for nearly all of the differences between sequences that have diverged by less than 2%: for these sequences the mean rate of divergence appears to be about 2%/Myr. In comparisons involving greater divergence times and greater sequence divergence, relatively more of the sequence differences are due to transversions. Specifically, the fraction of these differences that are counted as transversions rises from an initial value of less than 0.1 to a plateau value of nearly 0.6. The time required to reach half of the plateau value, about 10 Myr, is similar to that for mammalian mtDNA. The mtDNAs of flies and mammals are also alike in the shape of the curve relating the percentage of positions at which there are differences in protein-coding regions to the time of divergence. For both groups of animals, the curve has a steep initial slope ascribable to fast accumulation of synonymous substitutions and a shallow final slope resulting from the slow accumulation of substitutions causing amino acid replacements. However, the percentage of all sites that can experience a high rate of substitution appears to be only about 8% for fly mtDNA compared to about 20% for mammalian mtDNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

A fast method of comparing protein structures.

Comparative studies on protein structures form an integral part of protein crystallography. Here, a fast method of comparing protein structures is presented. Protein structures are represented as a set of secondary structural elements. The method also provides information regarding preferred packing arrangements and evolutionary dynamics of secondary structural elements. This information is not easily obtained from previous methods. In contrast to those methods, the present one can be used only for proteins with some secondary structure. The method is illustrated with globin folds, cytochromes and dehydrogenases as examples.

Animals↗

PubMed1987

The role of recombination and selection in the modifier theory of sex-ratio distortion.

The equilibrium configurations for a two-locus multialle model of sex-linked meiotic drive are studied with regard to the recombination fraction:limit cycles can occur in the case of small recombination while stable equilibrium points associated with linkage equilibrium can exist for an intermediate range of recombination values depending on the equilibrium sex ratio, linkage disequilibrium at nearby equilibrium points taking turn with loser linkage. The evolutionary dynamics in two-locus sex-ratio distortion systems is enlightened: while equilibria with a sex ratio closer to 1/2 are more likely to be stable with respect to perturbations on the frequencies of sex-ratio distorters that are represented at equilibrium, such equilibria are also more vulnerable to the invasion of mutant distorters when there is some degree of linkage with the sex-determining locus. For X-linked multimodifier systems of sex-ratio distortion, differential fertilities and viabilities are incorporated and a maximum principle is suggested.

Animals↗

PubMed1991

Coevolution of self-fertilization and inbreeding depression. I. Mutation-selection balance at one and two loci.

Simple theories for the evolution of breeding systems suggest that the fate of an allele that modifies the rate of self-fertilization hinges only on the degree to which selfing reduces opportunities for outcrossing ("pollen discounting") and the extent of inbreeding depression. These theories predict that outcrossing evolves whenever deleterious mutations have a more severe effect in combination than expected from their individual effects. We study the evolutionary dynamics of a modifier of the rate of self-fertilization in populations subject to complete pollen discounting and recurrent mutations which impair viability at a single locus in diploids and at two loci in haploids. Our analysis indicates that genetic associations arising immediately upon the introduction of a rare modifier allele generate substantial quantitative and qualitative departures from expectation. Higher rates of segregation under selfing in our one-locus diploid model generate positive associations between enhancers of selfing and wild-type viability alleles, which in turn favor the evolution of selfing under a wider range of conditions than expected. Greater opportunities for recombination under outcrossing in our two-locus haploid model generate positive associations between enhancers of outcrossing and wild-type viability alleles. These associations favor the evolution of outcrossing under a wider range of conditions, and introduce the possibility of stable mixed mating systems involving both selfing and outcrossing. Our explicit analysis of genetic associations between loci affecting viability and the rate of self-fertilization indicates that modifiers that enhance the production of offspring with very high (and very low) viability by promoting segregation or recombination develop positive associations with high viability. This advantage of producing extremes can compensate for an initial disadvantage in offspring number.

Alleles↗

PubMed1991

Coevolution of self-fertilization and inbreeding depression. II. Symmetric overdominance in viability.

We describe the evolutionary dynamics of a modifier of selfing coevolving with a locus subject to symmetric overdominance in viability under general levels of reduction in pollination success as a consequence of self-fertilization (pollen discounting). Simple models of the evolution of breeding systems that represent inbreeding depression as a constant parameter do not admit the possibility of stable mixed mating systems involving both inbreeding and random mating. Contrary to this expectation, we find that coevolution between a modifier of selfing and a single overdominant locus situated anywhere in the genome can generate evolutionarily attracting mixed mating systems. Two forms of association between the modifier locus and the viability locus promote the evolution of outcrossing. The favored heterozygous genotype at the viability locus develops positive associations with modifier alleles that enhance outcrossing and with the heterozygous genotype at the modifier locus. Associations between outcrossing and high viability evolve immediately upon the introduction of a rare modifier allele, even in the absence of linkage.

Alleles↗

PubMed2026

Lineage-specific adaptation and resistance in Candida albicans.

Candida albicans exhibits substantial phenotypic and ecological diversity; however, the exact relationship between its population structure, adaptation to specific niches, and antifungal resistance remains incompletely understood. To investigate these evolutionary dynamics, we analyzed the whole-genome sequences from 591 publicly available isolates, integrating nuclear and mitochondrial phylogenomics with ecological and resistance-associated genomic analyses. Phylogenomic analyses resolved 18 core nuclear clusters together with multiple admixed lineages. Strong cytonuclear concordance was noted in the majority of the central lineages, contrasting with a higher discordance among the admixed groups, consistent with recurrent genetic exchange. The analysis revealed that geographic origin explains a larger fraction of genetic variance than anatomical niche, supporting a predominantly generalist population structure. A notable exception was Cluster N16 (Candida africana), which presented a strict genital origin in our dataset (n = 34). Additionally, although the mitochondrial genome exhibits strong purifying selection, candidate residues under diversifying selection correlated with specific niches (e.g., bloodstream) have been identified. Analysis of five resistance-associated genes (ERG11, UPC2, FKS1, TAC1 and FUR1) revealed that resistance-associated variants were generally rare but exhibited distinct gene-specific patterns. In case of ERG11 and FUR1 they were concentrated in a specific clade (N11, N17, and their admixed Group A) and exhibit gene-dependent zygosity patterns. In summary, the evolution of C. albicans appears to be driven by a predominantly clonal model punctuated by episodic genetic exchange, where both ecological adaptation and antifungal resistance mutations exhibit genomic signatures marked by lineage specificity.

Antifungal resistance↗

PubMed2025

Fe-S cluster deficiency drives small colony variant formation in persistent infections.

INTRODUCTION: Small colony variants (SCVs) of Staphylococcus aureus (S. aureus) are associated with persistent infections and poor clinical outcomes. The mechanisms driving stable SCV formation remain poorly understood, particularly concerning metabolic adaptations. This study explores the in-host evolutionary dynamics of S. aureus and identifies a novel genetic determinant linked to SCV formation. OBJECTIVES: To investigate the genetic mutations and phenotypic adaptations underlying SCV formation, with a focus on the role of a novel mutation in the sufB gene, which is critical for Fe-S cluster biosynthesis. METHODS: Sequential isolates from a patient with recurrent infections were analyzed using whole-genome sequencing, antimicrobial susceptibility testing, and functional assays. The phylogenetic relationship of the isolates was determined, and specific mutations were identified. Functional assays included aconitase and glutamate synthase activity measurements, ATP level quantification, reactive oxygen species (ROS) production, and biofilm formation assays. In vivo pathogenesis was assessed using a murine catheter infection model. RESULTS: A novel frameshift mutation in sufB was identified, disrupting Fe-S cluster biosynthesis and impairing the TCA cycle and electron transport chain, leading to reduced ATP and ROS production. This metabolic reprogramming promoted stable SCV formation, characterized by slow growth, enhanced tolerance to antibiotics and neutrophil-mediated killing, and persistent inflammation in vivo. Restoration of sufB reversed these phenotypes, confirming its pivotal role in SCV-associated persistence. CONCLUSION: sufB is a novel genetic determinant of stable SCV formation through Fe-S cluster deficiency, driving metabolic shifts that enhance immune evasion and chronic infection. Our findings highlight antibiotic stewardship and suggest potential therapeutic strategies for managing persistent SCV-associated infections.

Staphylococcus aureus↗