Biology subjects

Mancera, E.

Publications and source records attributed to Mancera, E..

13 recordsLinked to original sources

bioRxiv2026

Widespread Saccharomyces hybridization in agave fermentations arises repeatedly from asymmetric parental diversity

Interspecific hybridization can profoundly reshape genomes by bringing together divergent genetic backgrounds, yet its ecological and evolutionary dynamics remain poorly understood at the population level. Here, we identify an extensive hybridization system in traditional agave fermentations across Mexico involving Saccharomyces cerevisiae, a species frequently associated with human-managed environments, and its predominantly wild relative S. paradoxus. A genomic survey reveals unexpectedly high hybrid frequencies in geographically distant regions with contrasting environments. Targeted sampling of distilleries and surrounding natural sites reveals a strong ecological bias, with hybrids recovered almost exclusively from distilleries, although both parental species occur in anthropogenic and natural habitats. Hybrid genomes show extensive architectural diversity, including distinct ploidies, variable parental genome contributions, variable patterns of heterozygosity, and contrasting mitochondrial ancestries. Phylogenomic and population-structure analyses of hybrid subgenomes demonstrate multiple independent origins. These recurrent events show pronounced asymmetry in parental genetic diversity. Hybrids derive from several S. cerevisiae populations, already shaped by extensive introgression, whereas every S. paradoxus subgenome traces to a single genetically differentiated S. paradoxus lineage found exclusively in distilleries, an unexpected association for a predominantly wild species. These findings establish agave fermentations as an exceptional system for studying recurrent interspecific hybridization and reveal how pronounced asymmetry in parental ancestry can shape hybrid formation.

evolutionary biology↗

bioRxiv2026

Chronological lifespan correlates with virulence within Candida albicans but long lifespan is not restricted to pathogenic Candida species

Yeast cells can remain viable for extended periods after entering stationary phase, a survival trait measured as chronological lifespan (CLS). Although CLS is well characterized in Saccharomyces cerevisiae as a model of postmitotic aging, its relevance to human-associated fungi remains poorly understood. Candida species of the CTG (CUG-Ser1) clade vary widely in ecology and clinical importance, raising the question of whether stationary-phase survival is linked to pathogenicity across species or among strains. Here, we combine an optimized CFU-based CLS assay with scalable flow cytometry of membrane integrity across Candida species and genetically diverse Candida albicans isolates. CLS varies extensively across species, yet caloric restriction extends survival in every species examined, revealing a remarkably consistent response to reduced glucose despite marked differences in baseline lifespan. Pathogenic species tend toward longer CLS, but long lifespan is not restricted to them, with the non-pathogenic C. sojae among the longest-lived species examined. Among 20 genetically diverse C. albicans clinical isolates, longer CLS is consistently associates with greater virulence. Our study establishes a methodological framework for comparative CLS analysis, reveals a broadly shared response to caloric restriction, and shows that the association between CLS and virulence emerges within C. albicans but not across Candida species.

microbiology↗

bioRxiv2026

Weight loss increases adipose dendritic cells, non-classical antigen presenting proteins, and cytotoxic effector cells

Weight cycling (i.e. cycles of weight gain, loss, and regain) is a growing health concern that has been shown to worsen risk of diabetes beyond that of obesity. Dendritic cells play a causal role in obesity-associated inflammation and metabolic disease. However, whether dendritic cells are impacted by weight cycling is not known. Here, we aimed to test the hypothesis that antigen presentation increases in dendritic cells with weight cycling. C57Bl/6J male mice were put on nutrient-matched low-fat or high-fat diets to elicit lean, weight gain, weight loss, and weight cycled groups. Adipose tissue immune cell populations and proteins related to signal 1, 2, and 3 of antigen presentation were analyzed by single cell-RNA sequencing and flow cytometry. Total adipose tissue dendritic cells, conventional type I and II dendritic cells, and monocyte-derived dendritic cells all increased with weight loss. Regarding major histocompatibility complex (MHC) protein expression, non-classical MHCIb proteins (Qa1, Qa2 and CD1d) were also highest in the weight loss group. Dendritic cells expressing the costimulatory molecule CD86 and the cytokine TNF were highest in the weight loss group. Finally, we assessed effector immune cell populations in the adipose tissue to understand the functional role of antigen presentation. CD8+ T cells, natural killer (NK) T cells, and NK cells also increased consistently with weight loss, but showed evidence of exhaustion. In sum, weight loss, but not weight cycling expands dendritic cells, increases signals for non-classical antigen presentation, and expands CD8+ T cells, NKT cells, and NK cells in the adipose tissue.

immunology↗

bioRxiv2026

Domestication and deep lineage divergence define two discrete trajectories in Kluyveromyces marxianus

Although genomics has greatly improved our ability to detect population structure and genetic divergence, it remains difficult to determine when diversity within a recognized species reflects continuous variation and when it marks the emergence of discrete evolutionary lineages. In yeasts, population-genomic studies often reveal overlapping signatures of environmental association, admixture, and domestication, making this distinction especially challenging. By analyzing 178 globally sampled genomes from Kluyveromyces marxianus, an emerging yeast of biotechnological interest, we show that diversity within this species resolves into two contrasting evolutionary trajectories that do not map onto broad geographic origin. Most industrial and clinical isolates belong to a lineage marked by gene loss, aneuploidy, and reduced fertility, consistent with genomic hallmarks of domestication. In contrast, isolates confined to traditional agave fermentations in Mexico and South Africa form a highly distinct lineage, separated from the other lineages by up to 4.8% genome-wide nucleotide divergence, widespread reciprocal monophyly, no detectable recent gene flow, and reduced mating compatibility despite co-occurrence with other lineages. Together, these results show that within a single yeast species, domestication-associated genome remodeling and deep lineage divergence can define distinct trajectories, with implications for strain selection in biotechnology.

evolutionary biology↗

bioRxiv2025

Hanseniaspora yeasts from agave fermentations provide insight into intraspecific gene loss

Hanseniaspora species stand out among yeasts for having the smallest genomes, marked by extensive gene family contractions. Consequently, they have been proposed as model organisms for studying the evolution of free-living cells lacking genes otherwise considered essential. Here, we show that Hanseniaspora yeasts are prevalent in agave fermentations used to produce traditional spirits across Mexico. We sequenced the genomes of 15 strains, unambiguously identifying them as H. lachancei, H. pseudoguilliermondii, H. guilliermondii, and H. opuntiae. Comparative genomic analyses revealed dynamic shifts in gene family sizes and compositions, suggesting ongoing gene loss within the fast-evolving branch of this genus. Notably, gene losses varied across functional categories, even among isolates of the same species. Growth assays across diverse stress conditions and carbon sources indicated that these genomic disparities do not directly translate into phenotypic differences. Together, our findings suggest that differential gene loss within species is an active evolutionary process shaping Hanseniaspora genomes, highlighting agave-fermentation populations as valuable models for studying genome reduction in a natural context.

genomics↗

bioRxiv2025

Ecological divergence of sympatric Saccharomyces species across wild and fermentative environments in the neotropics

The common yeast Saccharomyces cerevisiae is widely associated with anthropogenic habitats and dominates agave fermentations in Mexico, despite the absence of starter cultures in artisanal production. Yet, the origins and dispersal of the microorganisms involved in this fermentation system--including wild S. cerevisiae and its sister species S. paradoxus--remain poorly understood. Here, we analyzed the distribution of these two species across three regions in Mexico by collecting a total of 861 samples from 15 traditional distilleries and 25 nearby natural sites, including tree bark, insects, fermentation tanks, and distillery surfaces. Among 4,006 isolates identified by MALDI-TOF biotyping, S. cerevisiae and S. paradoxus were recovered at overall rates of 21% and 3.4%, respectively, with the former more frequently found in distilleries and the latter in natural habitats. Notably, Saccharomyces isolates were not exclusively associated with oak trees, as strains were also recovered from leguminous, pine, and Anacardiaceae trees, suggesting that the oak specialization observed in temperate regions may not hold in tropical environments. Genome sequencing of 100 Saccharomyces isolates and SNP-based analyses showed that S. cerevisiae strains clustered by geography, not by substrate, and were largely confined to two Mexican Agave clades, with minor representation from the North American Oak, Pacific West Coast, and Wine clades. Strains isolated from agave fermentations belonged to the same populations as those from plant substrates, with insects, especially Drosophilidae, likely mediating their dispersal. Meanwhile, S. paradoxus isolates grouped into the SpA (Eurasian) and SpB (North American) lineages, with three novel SpB subclades identified. Intriguingly, one of these, the SpB_MxAgave population, was exclusively associated with agave fermentations, providing the first evidence of a persistent association of S. paradoxus with an anthropogenic habitat. Our study sheds light on the ecological dynamics and diversity of S. cerevisiae and S. paradoxus populations in the neotropics.

microbiology↗

bioRxiv2024

Filamentation profile reveals several transcription regulators that contribute to differences between Candida albicans and Candida dubliniensis

Candida dubliniensis is the most closely related species to C. albicans, one of the leading causes of fungal infections in humans. However, despite sharing many characteristics, C. dubliniensis is significantly less pathogenic. To better understand the molecular underpinnings of these dissimilarities, we focused on the regulation of filamentation, a developmental trait fundamental for host colonization. We generated a collection of 44 C. dubliniensis null mutants of transcription regulators whose orthologs in C. albicans had been previously implicated in filamentous growth. These regulators are very similar at the sequence level, but phenotypic screening identified several mutants with contrasting interspecific filamentation phenotypes, beyond previously known differences. Bcr1, a well-known regulator of biofilm formation, stands out as its mutant only showed a filamentation defect in C. dubliniensis. Phenotypic and transcriptional characterization showed that the bcr1 defect is condition dependent and that this regulator plays a central role in the filamentation of C. dubliniensis, possibly by regulating the hyphal activator Ume6. Overall, our results suggest that several regulatory pathways are involved in the filamentation differences between C. albicans and C. dubliniensis and show that the C. dubliniensis mutant collection is a valuable resource to compare, at a molecular level, these two species of medical relevance. AUTHOR SUMMARYThe yeast Candida albicans is one of the most important fungal pathogens for humans. Its ability to form filamentous cells is central for the colonization of the human body. Although Candida dubliniensis, the closest known relative to C. albicans, is also able to filament, it is a much rarer cause of disease. Part of the virulence differences between these species have been attributed to their filamentation dissimilarities, but we are just starting to understand the regulatory pathways that control filamentation in C. dubliniensis. Here, we generated a collection of gene-deletion mutants in C. dubliniensis of the orthologs of transcription regulators that have been associated with filamentation in C. albicans. Comparative profile of the collection revealed that several regulators contribute to the filamentation dissimilarities between the two species. Among these, our results identified Bcr1 as a regulator with a prominent role controlling filamentation in C. dubliniensis, showing that its target genes have considerably changed between C. albicans and C. dubliniensis. Our findings and the collection of mutants that we generated open new opportunities to better understand the molecular mechanisms that underlie the pathogenicity of these clinically important microorganisms.

microbiology↗

bioRxiv2024

Recurrent introgression and geographical stratification shape Saccharomyces cerevisiae in the Neotropics

HighlightsO_LIPhylogenetic analyses of S. cerevisiae isolates from agave fermentation reveal novel clades within the Neotropical cluster. C_LIO_LIThe Neotropical cluster shows geographical population structure. C_LIO_LIMultiple pulses of interspecific introgression are part of the evolutionary history of S. cerevisiae in the Neotropics C_LI From yeasts to humans, introgressive hybridization significantly influences the evolutionary history of living organisms by introducing new genetic diversity. Strains of Saccharomyces cerevisiae worldwide exhibit introgressions from the sister species S. paradoxus, despite the average sequence identity between these species being lower than 90%. While S. cerevisiae isolates from the Neotropics are known for their high levels of introgression, the evolutionary events leading to the unusually high prevalence of them remain unclear. Here, we sequenced 216 S. cerevisiae isolates living in open agave fermentation across Mexico, a habitat at the interface of natural and industrial environments. The genomes of these strains revealed considerable genetic diversity and population structure linked to geographic distribution, which had been overlooked due to undersampling of this megadiverse region. These strains, along with those from French Guiana, Ecuador, and Brazil, form a broader Neotropical phylogenetic cluster that is notably enriched in introgressed DNA. Surprisingly, the origins and conservation patterns of introgressions indicate multiple hybridization events, suggesting an unprecedented scenario of flexible species barriers in this region. Our findings underscore concurrent evolutionary processes--geographical stratification and multiple introgressions--that shape the genomes of a diverse lineage of S. cerevisiae. Neotropical yeasts thus provide a natural laboratory for exploring the mechanisms and adaptive significance of introgressive hybridization in eukaryotic genome evolution.

evolutionary biology↗

bioRxiv2024

Microbial communities thriving in agave fermentations are locally influenced across diverse biogeographic regions

The production of traditional agave spirits in Mexico is a deeply rooted traditional process that relies on environmental microorganisms to ferment the cooked must from agave plants. Analysis of these microorganisms provides the opportunity to understand the dynamics of the microbial communities in the interface of natural and human-associated environments in a biologically and culturally rich region of the world. Here, we performed 16S and ITS amplicon sequencing of close to 100 fermentation tanks from 42 distilleries throughout Mexico. The Agave species used, production practices, climatic conditions, and biogeographic characteristics varied considerably among sites. Yet, we did find taxa present in most fermentations suggesting that there is a core of microorganisms that are hallmarks of these communities. These core taxa are represented by hundreds of OTUs showing large intra-specific variation. The only variable that was consistently associated with the composition of both bacterial and fungal communities was the distillery, suggesting that microbial composition is determined by the local production practices and unique attributes of each site. Fermentation stage, climate and producing region were also associated with the community composition, but only for prokaryotes. Analysis of microbial composition in several tanks within three distilleries also revealed taxa that were enriched in specific fermentation stages or agave species. Our work provides a comprehensive analysis of the microbiome of agave fermentations, contributing key knowledge for its management and conservation.

microbiology↗

bioRxiv2023

Genetic modification of Candida maltosa, a nonpathogenic CTG species, reveals EFG1 function

Candida maltosa is closely related to important pathogenic Candida species, but it has been rarely isolated from humans. Therefore, through comparative studies, it could be a powerful model to understand the pathogenicity underpinnings of Candida species. To facilitate studying C. maltosa at a molecular level, we built a cohesive genomic sequence composed of 45 scaffolds, a substantial improvement from the thousands of contigs of the available draft. Comparison with C. albicans and C. tropicalis revealed a reduction in the total number of genes in C. maltosa. However, gene loss seems not to be associated to its avirulence given that most pathogenicity genes were also present in C. maltosa. To genetically edit C. maltosa we generated triple auxotrophic strains so that gene deletions can be performed as has been routinely done in pathogenic species. As a proof of concept, we generated gene knockouts of Efg1, a transcription regulator involved in filamentation and biofilm formation in pathogenic species. Although in C. maltosa Efg1 also played a role in these processes, it seems to rather be a repressor of filamentation. The genome assembly and auxotrophic mutants developed are a key step to start using C. maltosa for comparative studies at a molecular level.

microbiology↗

bioRxiv2023

Yeast diversity in open agave fermentations across Mexico

Yeasts are a diverse group of fungal microorganisms that are widely used to produce fermented foods and beverages. In Mexico, open fermentations are used to obtain spirits from agave plants. Despite the prevalence of this traditional practice throughout the country, yeasts have only been isolated and studied from a limited number of distilleries. To systematically describe the diversity of yeast species from open agave fermentations, here we generate the YMX.1.0 culture collection by isolating 4,524 strains from 68 sites in diverse climatic, geographical, and biological contexts. We used MALDI-TOF mass spectrometry for taxonomic classification and a subset of the strains was verified by ITS and D1/D2 sequencing. The most abundant species isolated from all producing regions were Saccharomyces cerevisiae, Pichia kudriavzevii, Pichia manshurica, and Kluyveromyces marxianus. Despite the great diversity of environmental conditions and production practices the composition of yeast communities remained largely homogeneous throughout locations and fermentation stages, even if less abundant but commonly occurring yeasts were considered. Furthermore, ITS and D1/D2 sequencing revealed two candidate new species of Saccharomycetales. To explore the intraspecific variation of the yeasts from agave fermentations, we conducted genome sequencing on four isolates of the non-conventional yeast Kazachstania humilis. The genomes of these four strains were considerably distinct from other genomes of the same species, suggesting that they belong to a different population. Our work contributes to the understanding and conservation of an open fermentation system of great cultural and economic importance, providing a valuable resource to study the biology and genetic diversity of microorganisms living at the interface of natural and human-associated environments. TAKE AWAYO_LIWe isolated and identified 4,524 yeast strains from open agave fermentations in Mexico. C_LIO_LIYeast communities remained largely homogeneous throughout diverse locations. C_LIO_LIKazachstania humilis genomes differed significantly from isolates in other regions of the world. C_LIO_LIWe report two candidate new species related to the Pichia clade. C_LI

microbiology↗

bioRxiv2022

Genomewide identification of subtelomeric silencing factors in budding yeast

Subtelomeric gene silencing is the negative transcriptional regulation of genes located close to telomeres. This phenomenon occurs in a variety of eukaryotes with salient physiological implications, such as cell adherence, virulence, immune-system escape, and aging. The process has been widely studied in the budding yeast Saccharomyces cerevisiae, where genes involved in this process have been identified mostly on a gene-by-gene basis. Here, we introduce a quantitative approach to study subtelomeric gene silencing, that couples the classical URA3 reporter with GFP monitoring, amenable to high-throughput flow cytometry analysis. This reporter was integrated into several subtelomeric loci in the genome, where it showed a gradual range of silencing effects. By crossing strains with this dual reporter at the COS12 and YFR057W subtelomeric query loci with gene-deletion mutants, we carried out a genome-wide, comprehensive screen for subtelomeric-silencing factors. The approach was replicable and allowed detection of expression changes caused by previously described silencing factors. We also identified new molecular players affecting this process, most of which are related to functions underlying chromatin conformation. This was the case of LGE1, a novel silencing factor herein reported, associated with histone ubiquitination. Our strategy can be readily combined with other reporters and gene perturbation collections, making it a versatile tool to study gene silencing at a genome-wide scale.

genetics↗

bioRxiv2020

Evolution of the complex transcription network controlling biofilm formation in Candida species

We examine how a complex transcription network composed of seven "master" regulators and hundreds of target genes evolved over a span of approximately 70 million years. The network controls biofilm formation in several Candida species, a group of fungi that are present in humans both as constituents of the microbiota and as opportunistic pathogens. The ability to form biofilms is crucial for microbial colonization of different host niches, particularly when an implanted medical device is present. We examined and compared the network underlying biofilm formation across four Candida species (C. albicans, C. dubliniensis, C. tropicalis, and C. parapsilosis), all of which form biofilms composed of multiple cell types. To describe the salient features of the network across different species, we employed four approaches: (1) we phenotypically characterized the biofilms formed by these species using a variety of methods; (2) we knocked out -- one by one -- the master regulators identified in C. albicans in the four species and monitored their effect on biofilm formation; (3) we identified the target genes of 18 master regulator orthologs across the four species by performing ChIP-seq experiments; and (4) we carried out transcriptional profiling across each species during biofilm formation. Additional network information was obtained by analyzing an interspecies hybrid formed between the two most closely related species, C. albicans and C. dubliniensis. We observed two major types of changes that have occurred in the biofilm circuit since the four species last shared a common ancestor. Master regulator "substitutions" occurred over relatively long evolutionary times, resulting in different species having overlapping, but different sets of master regulators of biofilm formation. Second, massive changes in the connections between the master regulators and their target genes occurred over much shorter timescales. Both types of change are crucial to account for the structures of the biofilm networks in extant species. We believe this analysis is the first detailed, empirical description of how a complex transcription network has evolved.

evolutionary biology↗