Biology subjects

Hatmaker, E. A.

Publications and source records attributed to Hatmaker, E. A..

6 recordsLinked to original sources

bioRxiv2025

Population-Specific Transcriptomic Shifts Underlie Secondary Metabolic Diversification in Aspergillus flavus and the Domestication of Aspergillus oryzae

The genomic signatures of microbial domestication remain poorly understood within the context of natural population variation. Here, we demonstrate that Aspergillus oryzae, the filamentous fungus used in soy sauce production, shares more recent ancestry with a predominantly northern, largely non-aflatoxigenic population of Aspergillus flavus (population C). Strikingly, A. oryzae isolates also overlap with the recently described, clinically enriched A. flavus population D, suggesting the possibility of multiple domestication events. Although A. oryzae exhibits reduced virulence compared to A. flavus, all isolates tested retained pathogenicity in a zebrafish infection model. At the transcriptomic level, Aspergillus populations are significantly differentiated, with distinct responses to population density, indicating that population-specific transcriptomes adapt differently to ecological conditions. These differences extend beyond gene content and are not always explained by phylogenetic relationships, suggesting that phenotypic diversification occurs through the rapid reorganization of transcriptomic architectures. For example, A. oryzae displays significantly elevated expression of a module enriched for carbohydrate metabolism. Population-specific variation is also evident among secondary metabolite (SM) gene clusters. While A. oryzae shows markedly reduced expression of specific SM genes, particularly those involved in aflatoxin biosynthesis, this trend does not extend across the entire secondary metabolome. Using machine- learning-based gene regulatory network inference, we identified population-specific transcriptomic differences linked to distinct transcription factors, with evidence for both cis- and trans-acting regulatory divergence, but no changes in global regulators such as laeA. Together, these findings provide new insights into the domestication of A. oryzae, its global significance, and the microevolution of fungal secondary metabolic pathways. Significance StatementAspergillus flavus poses a significant threat to global agriculture by infecting crops and producing aflatoxin, a potent carcinogen that undermines food safety and international trade. The species is also a major human pathogen causing invasive fungal infections. Here, we demonstrate that A. flavus populations exhibit not only variations in their capacity to produce toxins but also in the way they regulate gene expression in response to environmental cues. These regulatory differences played a key role in the domestication of Aspergillus oryzae, a non-aflatoxigenic relative that has been safely used in food fermentation for centuries. Notably, while A. oryzae exhibits reduced aflatoxin biosynthetic gene expression, it expresses other secondary metabolite genes and retains limited opportunistic pathogenic potential. By revealing how transcriptomic rewiring drives population-level divergence, this work provides new insights into the evolution of toxin production, with broad implications for microbial domestication, crop protection, and global food security.

microbiology↗

bioRxiv2024

Pathogenicity is associated with population structure in a fungal pathogen of humans

Aspergillus flavus is a clinically and agriculturally important saprotrophic fungus responsible for severe human infections and extensive crop losses. We analyzed genomic data from 250 (95 clinical and 155 environmental) A. flavus isolates from 9 countries, including 70 newly sequenced clinical isolates, to examine population and pan-genome structure and their relationship to pathogenicity. We identified five A. flavus populations, including a new population, D, corresponding to distinct clades in the genome-wide phylogeny. Strikingly, > 75% of clinical isolates were from population D. Accessory genes, including genes within biosynthetic gene clusters, were significantly more common in some populations but rare in others. Population D was enriched for genes associated with zinc ion binding, lipid metabolism, and certain types of hydrolase activity. In contrast to the major human pathogen Aspergillus fumigatus, A. flavus pathogenicity in humans is strongly associated with population structure, making it a great system for investigating how population-specific genes contribute to pathogenicity.

evolutionary biology↗

bioRxiv2023

A comprehensive map of hotspots of de novo telomere addition in Saccharomyces cerevisiae

Telomere healing occurs when telomerase, normally restricted to chromosome ends, acts upon a double-strand break to create a new, functional telomere. De novo telomere addition on the centromere-proximal side of a break truncates the chromosome but, by blocking resection, may allow the cell to survive an otherwise lethal event. We previously identified several sequences in the bakers yeast, Saccharomyces cerevisiae, that act as hotspots of de novo telomere addition (termed Sites of Repair-associated Telomere Addition or SiRTAs), but the distribution and functional relevance of SiRTAs is unclear. Here, we describe a high-throughput sequencing method to measure the frequency and location of telomere addition within sequences of interest. Combining this methodology with a computational algorithm that identifies SiRTA sequence motifs, we generate the first comprehensive map of telomere-addition hotspots in yeast. Putative SiRTAs are strongly enriched in subtelomeric regions where they may facilitate formation of a new telomere following catastrophic telomere loss. In contrast, outside of subtelomeres, the distribution and orientation of SiRTAs appears random. Since truncating the chromosome at most SiRTAs would be lethal, this observation argues against selection for these sequences as sites of telomere addition per se. We find, however, that sequences predicted to function as SiRTAs are significantly more prevalent across the genome than expected by chance. Sequences identified by the algorithm bind the telomeric protein Cdc13, raising the possibility that association of Cdc13 with single-stranded regions generated during the response to DNA damage may facilitate DNA repair more generally.

genetics↗

bioRxiv2022

Evolution and codon usage bias of mitochondrial and nuclear genomes in Aspergillus section Flavi

The fungal genus Aspergillus contains a diversity of species divided into taxonomic sections of closely related species. Section Flavi contains 33 species, many of industrial, agricultural, or medical relevance. Here, we analyze the mitochondrial genomes (mitogenomes) of 20 Flavi species--including 18 newly assembled mitogenomes--and compare their evolutionary history and codon usage bias (CUB) patterns to their nuclear counterparts. CUB refers to variable frequencies of synonymous codons in coding DNA and is shaped by a balance of neutral processes and natural selection. All mitogenomes were circular DNA molecules with highly conserved gene content and order. As expected, genomic content, including GC content, and genome size differed greatly between mitochondrial and nuclear genomes. Phylogenetic analysis based on 14 concatenated mitochondrial genes predicted evolutionary relationships largely consistent with those predicted by a phylogeny constructed from 2,422 nuclear genes. Comparing similarities in interspecies patterns of CUB between mitochondrial and nuclear genomes showed that species grouped differently by patterns of CUB depending on whether analyses were performed using mitochondrial or nuclear relative synonymous usage values. We found that patterns of CUB at gene-level are more similar between mitogenomes of different species than the mitogenome and nuclear genome of the same species. Finally, we inferred that, although most genes--both nuclear and mitochondrial--deviated from the neutral expectation for codon usage, mitogenomes were not under translational selection while nuclear genomes were under moderate translational selection. These results contribute to the study of mitochondrial genome evolution in filamentous fungi.

evolutionary biology↗

bioRxiv2022

Genomic and phenotypic trait variation of the opportunistic human pathogen Aspergillus flavus and its non-pathogenic close relatives

Fungal diseases affect millions of humans annually, yet fungal pathogens remain understudied. The mold Aspergillus flavus is a causative agent of both aspergillosis and fungal keratitis infections, but species closely related to A. flavus are not considered clinically relevant. To study the evolution of A. flavus pathogenicity, we examined genomic and phenotypic traits of two strains of A. flavus and three closely related non- pathogenic species: Aspergillus arachidicola (two strains), Aspergillus parasiticus (two strains), and Aspergillus nomiae (one strain). We identified over 3,000 orthologous proteins unique to A. flavus, including seven biosynthetic gene clusters present in A. flavus strains and absent in the three non-pathogenic species. We chose to characterize secondary metabolite production for all seven strains under two clinically relevant conditions, temperature and salt concentration. Temperature impacted metabolite production in all species. Conversely, we found a lack of impact of salinity on secondary metabolite production. Strains of the same species produced different metabolites. Growth under stress conditions revealed additional heterogeneity within species. Using the invertebrate model of fungal disease Galleria mellonella, we found virulence of strains of the same species varied widely, and A. flavus strains were not more virulent than strains of the non-pathogenic species. In a murine model of fungal keratitis, we observed significantly lower disease severity and corneal thickness for A. arachidicola compared to other species at 48 hrs, but not at 72 hrs. Our work identifies key phenotypic, chemical, and genomic similarities and differences between the opportunistic human pathogen A. flavus and its non-pathogenic relatives.

evolutionary biology↗

bioRxiv2021

Genomes of gut bacteria from Nasonia wasps shed light on phylosymbiosis and microbe-assisted hybrid breakdown

Phylosymbiosis is a cross-system trend whereby microbial community relationships recapitulate the host phylogeny. In Nasonia parasitoid wasps, phylosymbiosis occurs throughout development, is distinguishable between sexes, and benefits host development and survival. Moreover, the microbiome shifts in hybrids as a rare Proteus bacteria in the microbiome becomes dominant. The larval hybrids then catastrophically succumb to bacterial-assisted lethality and reproductive isolation between the species. Two important questions for understanding phylosymbiosis and bacterial-assisted lethality in hybrids are: (i) Do the Nasonia bacterial genomes differ from other animal isolates and (ii) Are the hybrid bacterial genomes the same as those in the parental species? Here we report the cultivation, whole genome sequencing, and comparative analyses of the most abundant gut bacteria in Nasonia larvae, Providencia rettgeri and Proteus mirabilis. Characterization of new isolates shows Proteus mirabilis forms a more robust biofilm than Providencia rettgeri and when grown in co-culture, Proteus mirabilis significantly outcompetes Providencia rettgeri. Providencia rettgeri genomes from Nasonia are similar to each other and more divergent to pathogenic, human-associates strains. Proteus mirabilis from N. vitripennis, N. giraulti, and their hybrid offspring are nearly identical and relatively distinct from human isolates. These results indicate that members of the larval gut microbiome within Nasonia are most similar to each other, and the strain of the dominant Proteus mirabilis in hybrids is resident in parental species. Holobiont interactions between shared, resident members of the wasp microbiome and the host underpin phylosymbiosis and hybrid breakdown. IMPORTANCEAnimal and plant hosts often establish intimate relationships with their microbiomes. In varied environments, closely-related host species share more similar microbiomes, a pattern termed phylosymbiosis. When phylosymbiosis is functionally significant and beneficial, microbial transplants between host species or host hybridization can have detrimental consequences on host biology. In the Nasonia parasitoid wasp genus that contains a phylosymbiotic gut community, both effects occur and provide evidence for selective pressures on the holobiont. Here, we show that bacterial genomes in Nasonia differ from other environments and harbor genes with unique functions that may regulate phylosymbiotic relationships. Furthermore, the bacteria in hybrids are identical to parental species, thus supporting a hologenomic tenet that the same members of the microbiome and the host genome impact phylosymbiosis, hybrid breakdown, and speciation.

microbiology↗