About

Fred Samuel Dietrich is an Associate Professor of Molecular Genetics and Microbiology at Duke University. His research interests focus on using genomic technology to address fundamental biological questions related to fungi and human pathogens. His laboratory investigates the set of genes found in fungi, starting with the complete genome sequence of Saccharomyces cerevisiae, and characterizes genomes of related organisms such as Ashbya gossypii to define gene sets and identify gene loss. He explores genetic variation within fungal pathogen species, including Cryptococcus neoformans, to understand diversity and divergence among isolates. Additionally, his work involves applying bioinformatic and experimental tools to the human genome, establishing high-throughput sequencing capacities to address questions about human and mouse gene sets. Dietrich's background includes undergraduate studies in mathematics at UC Davis, graduate work at MIT in Gerry Fink’s lab, and contributions to the S. cerevisiae genome project at Stanford. He was recruited to Duke in July 2000, where his research emphasizes the genomic evolution of fungi, especially pathogenic species like Cryptococcus neoformans, and the interface between automated sequence acquisition and bioinformatics.

Research topics

• Biology
• Genetics
• Computational biology
• Ecology
• Molecular biology
• Microbiology
• Immunology

Selected publications

• Intrinsically disordered sequences can tune fungal growth and the cell cycle for specific temperatures

  UNC Libraries · 2025-08-01

  articleOpen access
  PublisherDOI

• Distinct evolutionary trajectories following loss of RNA interference in <i>Cryptococcus neoformans</i>

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-08-16 · 1 citations

  preprintOpen access

  Abstract While increased mutation rates typically have negative consequences in multicellular organisms, hypermutation can be advantageous for microbes adapting to the environment. Previously, we identified two hypermutator Cryptococcus neoformans clinical isolates that rapidly develop drug resistance due to transposition of a retrotransposon, Cnl1. Cnl1-mediated hypermutation is caused by a nonsense mutation in the gene encoding a novel RNAi component, Znf3, combined with a tremendous transposon burden. To elucidate adaptative mechanisms following RNAi loss, two bioinformatic pipelines were developed to identify RNAi loss-of-function mutations in a collection of 387 sequenced C. neoformans isolates. Remarkably, several RNAi-loss isolates were identified that are not hypermutators and have not accumulated transposons. To test if these RNAi loss-of-function mutations can cause hypermutation, the mutations were introduced into a non-hypermutator strain with a high transposon burden, which resulted in a hypermutator phenotype. To further investigate if RNAi-loss isolates can become hypermutators, in vitro passaging was performed. Although no hypermutators were found in two C. neoformans RNAi-loss strains after short-term passage, hypermutation was observed in a passaged C. deneoformans strain with increased transposon burden. Consistent with a two-step evolution, when an RNAi-loss isolate was crossed with an isolate containing a high Cnl1 burden, F1 hypermutator progeny inheriting a high transposon burden were identified. In addition to Cnl1 transpositions, insertions of a novel gigantic DNA transposon KDZ1 (∼11 kb), contributed to hypermutation in the progeny. Our results suggest that RNAi loss is relatively common (7/387, ∼1.8%) and enables distinct evolutionary trajectories: hypermutation following transposon accumulation or survival without hypermutation. Significance Statement There is a dearth of antifungal drugs available to treat Cryptococcus neoformans , a human fungal pathogen of global impact. We previously identified natural hypermutators with a loss-of-function mutation in the RNAi machinery and transposon expansion. Here, we identified several novel natural isolates with RNAi defects, none of which are hypermutators or have undergone transposon expansion. Furthermore, we demonstrate that these isolates can lie on a pathway to hypermutation following introduction of a transposon burden. In addition, a novel DNA transposon class was discovered that contributes to antifungal drug resistance. These findings highlight the importance of transposons in driving rapid adaptation in the absence of RNAi and reveal distinct evolutionary trajectories following RNAi loss, a relatively common event in C. neoformans .

  PublisherOA PDFDOI

• Distinct evolutionary trajectories following loss of RNA interference in <i>Cryptococcus neoformans</i>

  Proceedings of the National Academy of Sciences · 2024-11-13 · 15 citations

  articleOpen access

  While increased mutation rates typically have negative consequences in multicellular organisms, hypermutation can be advantageous for microbes adapting to the environment. Previously, we identified two hypermutator Cryptococcus neoformans clinical isolates that rapidly develop drug resistance due to transposition of a retrotransposon, Cnl1. Cnl1-mediated hypermutation is caused by a nonsense mutation in a gene encoding an RNA interference (RNAi) component, ZNF3 , combined with a tremendous transposon burden. To elucidate adaptive mechanisms following RNAi loss, two bioinformatic pipelines were developed to identify RNAi loss-of-function (LOF) mutations in a collection of 387 sequenced C. neoformans isolates. Remarkably, several RNAi-loss isolates were identified that are not hypermutators and have not accumulated transposons. To test whether these RNAi LOF mutations can cause hypermutation, the mutations were introduced into a nonhypermutator strain with a high transposon burden, which resulted in a hypermutator phenotype. To further investigate whether RNAi-loss isolates can become hypermutators, in vitro passaging was performed. Although no hypermutators were found in two C. neoformans RNAi-loss strains after short-term passage, hypermutation was observed in a passaged Cryptococcus deneoformans strain with an increased transposon burden. Consistent with a two-step evolution, when an RNAi-loss isolate was crossed with an isolate containing a high Cnl1 burden, F1 hypermutator progeny inheriting a high transposon burden were identified. In addition to Cnl1 transpositions, insertions of a gigantic DNA transposon KDZ1 (~11 kb) contributed to hypermutation in the progeny. Our results suggest that RNAi loss is relatively common (7/387, ~1.8%) and enables distinct evolutionary trajectories: hypermutation following transposon accumulation or survival without hypermutation.

  PublisherOA PDFDOI

• Intrinsically disordered sequences can tune fungal growth and the cell cycle for specific temperatures

  Current Biology · 2024-07-31 · 12 citations

  articleOpen access
  PublisherOA PDFDOI

• Core gene set of the species <i>Saccharomyces cerevisiae</i>

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-09-08 · 1 citations

  preprintOpen access1st authorCorresponding

  Abstract Examination of the genome sequence of Saccharomyces cerevisiae strain S288c and 93 additional diverse strains allows identification of the 5885 genes that make up the core set of genes in this species and gives a better sense of the organization and plasticity of this genome. S. cerevisiae strains each contain dozens to hundreds of strain-specific genes. In addition to a variable content of retrotransposons Ty1-Ty6, some strains contain a novel transposable element, Ty7. Examination further shows that some annotated putative protein coding genes are likely artifacts. We propose altering approximately 5% of the current annotations in the widely used reference strain S288c. Potential null alleles are common and found in all 94 strains examined, with these potential null alleles typically containing a single stop codon or frameshift. There are also gene remnants, pseudogenes, and variable arrays of genes. Among the core genes there are now only 364 protein coding genes of unknown function, classified as uncharacterized in the Saccharomyces Genome Database. This work suggests that there is a role for carefully edited and annotated genome sequences in understanding the genome organization and content of a species. We propose that gene remnants be added to the repertoire of features found in the S. cerevisiae genome, and likely other fungal species.

  PublisherOA PDFDOI

• Biomolecular condensates in fungi are tuned to function at specific temperatures

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-11-27 · 1 citations

  preprintOpen access

  Summary Temperature can impact every reaction and molecular interaction essential to a cell. For organisms that cannot regulate their own temperature, a major challenge is how to adapt to temperatures that fluctuate unpredictability and on variable timescales. Biomolecular condensation offers a possible mechanism for encoding temperature-responsiveness and robustness into cell biochemistry and organization. To explore this idea, we examined temperature adaptation in a filamentous-growing fungus called Ashbya gossypii that engages biomolecular condensates containing the RNA-binding protein Whi3 to regulate mitosis and morphogenesis. We collected wild isolates of Ashbya that originate in different climates and found that mitotic asynchrony and polarized growth, which are known to be controlled by the condensation of Whi3, are temperature sensitive. Sequence analysis in the wild strains revealed changes to specific domains within Whi3 known to be important in condensate formation. Using an in vitro condensate reconstitution assay we found that temperature impacts the relative abundance of protein to RNA within condensates and that this directly impacts the material properties of the droplets. Finally, we found that exchanging Whi3 genes between warm and cold isolates was sufficient to rescue some, but not all, condensate-related phenotypes. Together these data demonstrate that material properties of Whi3 condensates are temperature sensitive, that these properties are important for function, and that sequence optimizes properties for a given climate.

  PublisherOA PDFDOI

• RNA viruses, M satellites, chromosomal killer genes, and killer/nonkiller phenotypes in the 100-genomes <i>S. cerevisiae</i> strains

  G3 Genes Genomes Genetics · 2023-07-27 · 10 citations

  articleOpen access

  We characterized previously identified RNA viruses (L-A, L-BC, 20S, and 23S), L-A-dependent M satellites (M1, M2, M28, and Mlus), and M satellite-dependent killer phenotypes in the Saccharomyces cerevisiae 100-genomes genetic resource population. L-BC was present in all strains, albeit in 2 distinct levels, L-BChi and L-BClo; the L-BC level is associated with the L-BC genotype. L-BChi, L-A, 20S, 23S, M1, M2, and Mlus (M28 was absent) were in fewer strains than the similarly inherited 2µ plasmid. Novel L-A-dependent phenotypes were identified. Ten M+ strains exhibited M satellite-dependent killing (K+) of at least 1 of the naturally M0 and cured M0 derivatives of the 100-genomes strains; in these M0 strains, sensitivities to K1+, K2+, and K28+ strains varied. Finally, to complement our M satellite-encoded killer toxin analysis, we assembled the chromosomal KHS1 and KHR1 killer genes and used naturally M0 and cured M0 derivatives of the 100-genomes strains to assess and characterize the chromosomal killer phenotypes.

  PublisherOA PDFDOI

• Biomolecular Condensates in Fungi are Tuned to Function at Specific Temperatures

  SSRN Electronic Journal · 2023-01-01 · 1 citations

  preprintOpen access
  PublisherDOI

• A second decade of overwintering hummingbirds in Florida and Alabama

  The Wilson Journal of Ornithology · 2021-03-01 · 2 citations

  articleSenior author

  For a second decade, from November 2008 to March 2018, we examined the species diversity, return rate, longevity, and migration routes of hummingbirds overwintering in southern Alabama and the panhandle, northern peninsula, and central peninsula of Florida. We captured and banded 11 species of hummingbirds (n= 1,870 individuals), including 931 Rufous Hummingbirds (Selasphorus rufus; 49%), 583 Ruby-throated Hummingbirds (Archilochus colubris; 31%), 219 Black-chinned Hummingbirds (A. alexandri; 12%), 49 Buff-bellied Hummingbirds (Amazilia yucatanensis), 49 Calliope Hummingbirds (S. calliope), 19 Allen's Hummingbirds (S. sasin), 11 Broad-tailed Hummingbirds (S. platycercus), 6 Broad-billed Hummingbirds (Cynanthus latriostris), 1 Anna's Hummingbird (Calypte anna), 1 Costa's Hummingbird (Calypte costae), and 1 White-eared Hummingbird (Hylocharis leucotis). Site fidelity was high, with 299 hummingbirds of 5 species returning at least once. Two Rufous Hummingbirds migrated to our study area in the autumn from the West (Oklahoma and Texas). One Ruby-throated Hummingbird banded in Lakeland, Florida, was recovered in Utopia, New Brunswick, Canada, suggesting the overwintering Ruby-throated Hummingbirds in our study area are migratory and not sedentary.

  PublisherDOI

• Comparative analysis of RNA enrichment methods for preparation of <i>Cryptococcus neoformans</i> RNA sequencing libraries

  bioRxiv (Cold Spring Harbor Laboratory) · 2021-03-02 · 1 citations

  preprintOpen access

  ABSTRACT Ribosomal RNA (rRNA) is the major RNA constituent of cells, therefore most RNA sequencing (RNA-Seq) experiments involve removal of rRNA. This process, called RNA enrichment, is done primarily to reduce cost: without rRNA removal, deeper sequencing would need to be performed to balance the sequencing reads wasted on rRNA. The ideal RNA enrichment method would remove all rRNA without affecting other RNA in the sample. We have tested the performance of three RNA enrichment methods on RNA isolated from Cryptococcus neoformans , a fungal pathogen of humans. We show that the RNase H depletion method unambiguously outperforms the commonly used Poly(A) isolation method: the RNase H method more efficiently depletes rRNA while more accurately recapitulating the expression levels of other RNA observed in an unenriched “gold standard”. The RNase H depletion method is also superior to the Ribo-Zero depletion method as measured by rRNA depletion efficiency and recapitulation of protein-coding gene expression levels, while the Ribo-Zero depletion method performs moderately better in preserving non-coding RNA (ncRNA). Finally, we have leveraged this dataset to identify novel long non-coding RNA (lncRNA) genes and to accurately map the C. neoformans mitochondrial rRNA genes. ARTICLE SUMMARY We compare the efficacy of three different RNA enrichment methods for RNA-Seq in Cryptococcus neoformans : RNase H depletion, Ribo-Zero depletion, and Poly(A) isolation. We show that the RNase H depletion method, which is evaluated in C. neoformans samples for the first time here, is highly efficient and specific in removing rRNA. Additionally, using data generated through these analyses, we identify novel long non-coding RNA genes in C. neoformans . We conclude that RNase H depletion is an effective and reliable method for preparation of C. neoformans RNA-Seq libraries.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01NS042263

  NIH · $1.5M · 2008

• NIH Grant R01GM098287

  NIH · $2.1M · 2016

Frequent coauthors

• Joseph Heitman

  Duke University Hospital

  90 shared

• Peter Philippsen

  University of Basel

  61 shared

• Sophie Brachat

  Novartis (Switzerland)

  60 shared

• Sylvia Voegeli

  University of Basel

  56 shared

• Philippe P. Luedi

  Duke University Hospital

  56 shared

• Krista Gates

  51 shared

• Rainer Pöhlmann

  Duke University

  50 shared

• Sabine Steiner

  University of Basel

  50 shared