Jacob Lucas Steenwyk

Jacob Lucas Steenwyk
University of California, Berkeley | UCB · Department of Molecular and Cell Biology

Doctor of Philosophy
Investigating genome function and evolution

About

103
Publications
20,259
Reads
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1,326
Citations
Introduction
https://jlsteenwyk.com My research, conducted as part of the Antonis Rokas Lab at Vanderbilt University, aims to utilize various 'omics approaches to understand the evolution and function of fungal genomes. These analyses inform the evolution and/or divergence of traits important to our lives such as pathogenicity. More generally, I am most interested in how populations and/or species evolve, diverge, and what genomic elements and traits define them.
Additional affiliations
May 2016 - August 2022
Vanderbilt University
Position
  • PhD Student
Education
August 2015 - May 2016
Clark University
Field of study
  • Biochemistry and Molecular Biology
August 2011 - May 2015
Clark University
Field of study
  • Biochemistry and Molecular Biology

Publications

Publications (103)
Article
Full-text available
Invasive aspergillosis is a deadly fungal disease; more than 400,000 patients are infected worldwide each year and the mortality rate can be as high as 50-95%. Of the ~450 species in the genus Aspergillus only a few are known to be clinically relevant, with the major pathogen Aspergillus fumigatus being responsible for ~50% of all invasive mold inf...
Article
Full-text available
Aspergillus fumigatus is both an environmental saprobe and an opportunistic human fungal pathogen. Knowledge of genomic variation across A. fumigatus isolates is essential for understanding the evolution of pathogenicity, virulence, and resistance to antifungal drugs. Here, we investigated 206 A. fumigatus isolates (133 clinical and 73 environmenta...
Article
Bioinformatic analysis-such as genome assembly quality assessment, alignment summary statistics, relative synonymous codon usage, file format conversion, and processing and analysis-is integrated into diverse disciplines in the biological sciences. Several command-line pieces of software have been developed to conduct some of these individual analy...
Article
The evolutionary rates of functionally related genes often covary. We present a gene coevolution network inferred from examining nearly 3 million orthologous gene pairs from 332 budding yeast species spanning ~400 million years of evolution. Network modules provide insight into cellular and genomic structure and function. Examination of the phenoty...
Preprint
Mutations fuel the diversity of life forms on earth through changes of nucleotides in DNA sequence. Patterns of mutations are biased; for example, mutational biases toward adenine and thymine have been previously noted in bacteria and biases for transitions over transversions are observed in diverse groups of organisms. However, the mutational bias...
Preprint
Aspergillus fumigatus is both an environmental saprobe and an opportunistic human fungal pathogen. Knowledge of genomic variation across A. fumigatus isolates is essential for understanding the evolution of pathogenicity, virulence, and resistance to antifungal drugs. Here, we investigated 206 A. fumigatus isolates (133 clinical and 73 environmenta...
Article
Full-text available
Unique DNA repair enzymes that provide self-resistance against therapeutically important, genotoxic natural products have been discovered in bacterial biosynthetic gene clusters (BGCs). Among these, the DNA glycosylase AlkZ is essential for azinomycin B production and belongs to the HTH-42 superfamily of uncharacterized proteins. Despite their wide...
Article
Full-text available
Aspergillus fumigatus causes a range of human and animal diseases collectively known as aspergillosis. A. fumigatus possesses and expresses a range of genetic determinants of virulence, which facilitate colonisation and disease progression, including the secretion of mycotoxins. Gliotoxin (GT) is the best studied A. fumigatus mycotoxin with a wide...
Article
Full-text available
Clear and effective figures are central to successfully communicating scientific data. Here, we present ggpubfigs, an R package with colorblind-friendly color palettes and extensions of the ggplot2 graphic system, which helps make publication-quality scientific figures from quantitative data; ggpubfigs is an open-source and user-friendly tool that...
Preprint
Molecular evolution studies, such as phylogenomic studies and genome-wide surveys of positive selection, often rely on gene families of single-copy orthologs (SC-OGs). In contrast, large gene families with multiple homologs in one or more species - a phenomenon observed among several important families of genes such as transporters and transcriptio...
Preprint
Unique DNA repair enzymes that provide self-resistance against genotoxic natural products have been discovered recently in bacterial biosynthetic gene clusters (BGCs). The DNA glycosylase AlkZ belongs to a superfamily of uncharacterized proteins found in antibiotic producers and pathogens, but despite its importance to azinomycin B resistance, the...
Preprint
Invasive aspergillosis is a deadly fungal disease; more than 400,000 patients are infected worldwide each year and the mortality rate can be as high as 50-95%. Of the ~450 species in the genus Aspergillus only a few are known to be clinically relevant, with the major pathogen Aspergillus fumigatus being responsible for ~50% of all invasive mold inf...
Preprint
Full-text available
Bioinformatic analysis-such as genome assembly quality assessment, alignment summary statistics, relative synonymous codon usage, paired-end aware quality trimming and filtering of sequencing reads, file format conversion, and processing and analysis-is integrated into diverse disciplines in the biological sciences. Several command-line pieces of s...
Article
Full-text available
The DNA mismatch repair (MMR) pathway corrects mismatched bases produced during DNA replication and is highly conserved across the tree of life, reflecting its fundamental importance for genome integrity. Loss of function in one or a few MMR genes can lead to increased mutation rates and microsatellite instability, as seen in some human cancers. Wh...
Article
Full-text available
Certain Aspergillus fungi cause aspergillosis, a set of diseases that typically affect immunocompromised individuals. Most cases of aspergillosis are caused by Aspergillus fumigatus , which infects millions of people annually. Some closely related so-called cryptic species, such as Aspergillus lentulus , can also cause aspergillosis, albeit at lowe...
Preprint
Full-text available
Aspergillus fumigatus causes a range of human and animal diseases collectively known as aspergillosis. A. fumigatus possesses and expresses a range of genetic determinants of virulence, which facilitate colonisation and disease progression, including the secretion of mycotoxins. Gliotoxin (GT) is the best studied A. fumigatus mycotoxin with a wide...
Article
Full-text available
Aspergillus fumigatus is a major opportunistic fungal pathogen of immunocompromised and immunocompetent hosts. To successfully establish an infection, A. fumigatus needs to use host carbon sources, such as acetate, present in the body fluids and peripheral tissues. However, utilization of acetate as a carbon source by fungi in the context of infect...
Article
Full-text available
Identification and retrieval of genes of interest from genomic data is an essential step for many bioinformatic applications. We present orthofisher, a command-line tool for automated identification and retrieval of genes with high sequence similarity to a query profile-Hidden Markov Model sequence alignment across a set of proteomes. Performance a...
Preprint
Full-text available
Gene coevolution - which refers to gene pairs whose evolutionary rates covary across speciation events - is often observed among functionally related genes. We present a comprehensive gene coevolution network inferred from the examination of nearly three million gene pairs from 332 budding yeast species spanning ~400 million years of eukaryotic evo...
Preprint
Full-text available
Aspergillus fumigatus is a major opportunistic fungal pathogen of immunocompromised and immunocompetent hosts. To successfully establish an infection, A. fumigatus needs to use host carbon sources, such as acetate, present in the body fluids and peripheral tissues. However, utilisation of acetate as a carbon source by fungi in the context of infect...
Article
Full-text available
The ongoing global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for coronavirus disease 2019 (COVID-19), first described in Wuhan, China. A subset of COVID-19 patients has been reported to have acquired secondary infections by microbial pathogens, such as opportunistic fungal pathogens from the...
Article
Full-text available
Aspergillosis is an important opportunistic human disease caused by filamentous fungi in the genus Aspergillus. Roughly 70% of infections are caused by Aspergillus fumigatus, with the rest stemming from approximately a dozen other Aspergillus species. Several of these pathogens are closely related to A. fumigatus and belong in the same taxonomic se...
Article
Full-text available
Reverse ecology is the inference of ecological information from patterns of genomic variation. One rich, heretofore underutilized, source of ecologically relevant genomic information is codon optimality or adaptation. Bias toward codons that match the tRNA pool is robustly associated with high gene expression in diverse organisms, suggesting that c...
Preprint
Full-text available
The DNA mismatch repair (MMR) pathway corrects mismatched bases produced during DNA replication and is highly conserved across the tree of life, reflecting its fundamental importance for genome integrity. Loss of function in one or a few MMR genes can lead to increased mutation rates and microsatellite instability, as seen in some human cancers. Wh...
Article
Full-text available
Cell cycle checkpoints and DNA repair pathways contribute to maintaining genome integrity and are thought to be evolutionarily ancient and broadly conserved. For example, in the yeast Saccharomyces cerevisiae and humans, DNA damage induces activation of a checkpoint effector kinase, Rad53p (human homolog Chk2), to promote cell cycle arrest and tran...
Preprint
Full-text available
Aspergillosis is an important opportunistic human disease caused by filamentous fungi in the genus Aspergillus . Roughly 70% of infections are caused by Aspergillus fumigatus , with the rest stemming from approximately a dozen other Aspergillus species. Several of these pathogens are closely related to A. fumigatus and belong in the same taxonomic...
Article
Full-text available
Topological conflict or incongruence is widespread in phylogenomic data. Concatenation- and coalescent-based approaches often result in incongruent topologies, but the causes of this conflict can be difficult to characterize. We examined incongruence stemming from conflict between likelihood-based signal (quantified by the difference in gene-wise l...
Article
Full-text available
Motivation: Diverse disciplines in biology process and analyze multiple sequence alignments (MSAs) and phylogenetic trees to evaluate their information content, infer evolutionary events and processes, and predict gene function. However, automated processing of MSAs and trees remains a challenge due to the lack of a unified toolkit. To fill this g...
Article
Phylogenomic studies using genome-scale amounts of data have greatly improved understanding of the tree of life. Despite the diversity, ecological significance, and biomedical and industrial importance of fungi, evolutionary relationships among several major lineages remain poorly resolved, especially those near the base of the fungal phylogeny. To...
Article
Full-text available
Andy Warhol‐like portrait of budding yeasts by Jacob L. Steenwyk (https://jlsteenwyk.com/arts.html). For further details, readers are referred to the article by Steenwyk on page 55 of this issue.
Article
Full-text available
Highly divergent sites in multiple sequence alignments (MSAs), which can stem from erroneous inference of homology and saturation of substitutions, are thought to negatively impact phylogenetic inference. Thus, several different trimming strategies have been developed for identifying and removing these sites prior to phylogenetic inference. However...
Article
Full-text available
used the alignment-free feature frequency profile (FFP) method to reconstruct a broad sketch of the tree of life (ToL). The FFP tree reports many relationships that strongly contradict the current consensus view of the ToL, including sister group relationships for plants + animals, Bacteria + Archaea, and Mollusca (incorrectly referred to as cnidar...
Preprint
Full-text available
The ongoing global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) first described from Wuhan, China. A subset of COVID-19 patients has been reported to have acquired secondary infections by microbial pathogens, such as fungal opportunistic pathogens from...
Article
Full-text available
Ascomycota, the largest and most well-studied phylum of fungi, contains three subphyla: Saccharomycotina (budding yeasts), Pezizomycotina (filamentous fungi), and Taphrinomycotina (fission yeasts). Despite its importance, we lack a comprehensive genome-scale phylogeny or understanding of the similarities and differences in the mode of genome evolut...
Preprint
Full-text available
Diverse disciplines in biology process and analyze multiple sequence alignments (MSAs) and phylogenetic trees to evaluate their information content, infer evolutionary events and processes, and predict gene function. However, automated processing of MSAs and trees remains a challenge due to the lack of a unified toolkit. To fill this gap, we introd...
Article
Full-text available
Aspergillus fungi in section Fumigati include important human pathogens. Here, we sequenced the genomes of two strains of Aspergillus hiratsukae and two strains of Aspergillus felis The average genome sizes are 29.5 Mb for A. hiratsukae and 31.8 Mb for A. felis.
Preprint
Full-text available
Phylogenomic studies based on genome-scale amounts of data have greatly improved understanding of the tree of life. Despite their diversity, ecological significance, and biomedical and industrial importance, large-scale phylogenomic studies of Fungi are lacking. Furthermore, several evolutionary relationships among major fungal lineages remain cont...
Article
Full-text available
Aspergillus fumigatus is a major human pathogen. In contrast, Aspergillus fischeri and the recently described Aspergillus oerlinghausenensis , the two species most closely related to A. fumigatus , are not known to be pathogenic. Some of the genetic determinants of virulence (or "cards of virulence") that A . fumigatus possesses are secondary metab...
Preprint
Full-text available
G-protein coupled receptors (GPCRs) are extracellular signalling receptors that sense environmental cues to coordinate a biological response. Fungi sense their environment primarily through GPCR-mediated signalling pathways, which in turn regulate fungal development, metabolism, virulence and mycotoxin biosynthesis. A. fumigatus is an important hum...
Preprint
Full-text available
Reverse ecology is the inference of ecological information from patterns of genomic variation. One rich, heretofore underutilized, source of ecologically-relevant genomic information is codon optimality or adaptation. Bias toward codons that match the tRNA pool is robustly associated with high gene expression in diverse organisms, suggesting that c...
Article
Full-text available
Aspergillus fumigatus is an opportunistic fungal pathogen that secretes an array of immune-modulatory molecules, including secondary metabolites (SMs), which contribute to enhancing fungal fitness and growth within the mammalian host. Gliotoxin (GT) is a SM that interferes with the function and recruitment of innate immune cells, which are essentia...
Preprint
Full-text available
Choi and Kim (PNAS, 117: 3678-3686; first published February 4, 2020; https://doi.org/10.1073/pnas.1915766117) used the alignment-free Feature Frequency Profile (FFP) method to reconstruct a broad sketch of the tree of life based on proteome data from 4,023 taxa. The FFP-based reconstruction reports many relationships that strongly contradict the c...
Preprint
Full-text available
Highly divergent sites in multiple sequence alignments, which stem from erroneous inference of homology and saturation of substitutions, are thought to negatively impact phylogenetic inference. Trimming methods aim to remove these sites before phylogenetic inference, but recent analysis suggests that doing so can worsen inference. We introduce Clip...
Article
Interspecific hybridization substantially alters genotypes and phenotypes and can give rise to new lineages. Hybrid isolates that differ from their parental species in infection-relevant traits have been observed in several human-pathogenic yeasts and plant-pathogenic filamentous fungi but have yet to be found in human-pathogenic filamentous fungi....
Article
Full-text available
Gene regulatory networks (GRNs) drive developmental and cellular differentiation, and variation in their architectures gives rise to morphological diversity. Pioneering studies in Aspergillus fungi, coupled with subsequent work in other filamentous fungi, have shown that the GRN governed by the BrlA, AbaA, and WetA proteins controls the development...
Preprint
Full-text available
Ascomycota, the largest and best-studied phylum of fungi, contains three subphyla: Saccharomycotina (budding yeasts), Pezizomycotina (filamentous fungi), and Taphrinomycotina (fission yeasts); organisms from all three subphyla have been invaluable as models in diverse fields (e.g., biotechnology, cell biology, genetics, and medicine). Despite its i...
Article
Full-text available
Fungal pathogens are a global threat to human health. For example, fungi from the genus Aspergillus cause a spectrum of diseases collectively known as aspergillosis. Most of the >200,000 life-threatening aspergillosis infections per year worldwide are caused by Aspergillus fumigatus. Recently, molecular typing techniques have revealed that aspergil...
Preprint
Full-text available
Aspergillus fumigatus is a major human pathogen that causes hundreds of thousands of infections yearly with high mortality rates. In contrast, Aspergillus fischeri and the recently described Aspergillus oerlinghausenensis , the two species most closely related to A. fumigatus , are not known to be pathogenic. Some of the “cards of virulence” that A...
Article
Full-text available
Aspergillus nidulans is an opportunistic fungal pathogen in patients with immunodeficiency, and virulence of A. nidulans isolates has mainly been studied in the context of chronic granulomatous disease (CGD), with characterization of clinical isolates obtained from non-CGD patients remaining elusive. This study therefore carried out a detailed biol...
Preprint
Full-text available
Fungal pathogens are a global threat to human health. For example, fungi from the genus Aspergillus cause a spectrum of diseases collectively known as aspergillosis. Most of the >200,000 life-threatening aspergillosis infections per year worldwide are caused by Aspergillus fumigatus . Recently, molecular typing techniques have revealed that aspergi...
Article
Full-text available
“Biology is more like history than it is like physics. You have to know the past to understand the present.”–Carl Sagan (1980). © 2020 Rokas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the origina...
Article
Full-text available
Aspergillus fumigatus is a major opportunistic fungal pathogen of humans, but most of its close relatives are nonpathogenic. Why is that so? This important, yet largely unanswered, question can be addressed by examining how A. fumigatus and its close nonpathogenic relatives are similar or different with respect to virulence-associated traits. We in...
Article
Full-text available
Genomic studies of yeasts from the wild have increased considerably in the last few years. This revolution has been fueled by advances in high-throughput sequencing technologies and a better understanding of yeast ecology and phylogeography, especially for biotechnologically important species. The present review aims to first introduce new bioinfor...
Preprint
Full-text available
Aspergillus nidulans is an opportunistic fungal pathogen in patients with immunodeficiency and virulence of A. nidulans isolates has mainly been studied in the context of the chronic granulomatous disease (CGD), with characterization of clinical isolates obtained from non-CGD patients remaining elusive. This study therefore carried out a detailed b...
Article
Full-text available
Covering: up to 2019 Fungi produce a remarkable diversity of secondary metabolites: small, bioactive molecules not required for growth but which are essential to their ecological interactions with other organisms. Genes that participate in the same secondary metabolic pathway typically reside next to each other in fungal genomes and form biosynthet...
Preprint
Full-text available
Aspergillus fumigatus is a major opportunistic human pathogen. Multiple traits contribute to A. fumigatus pathogenicity, including its ability to produce specific secondary metabolites, such as gliotoxin. Gliotoxin is known to inhibit the host immune response, and genetic mutants that inactivate gliotoxin biosynthesis (or secondary metabolism in ge...
Article
Full-text available
Objective Phylogenetic trees that contain hundreds to thousands of taxa are now routinely generated. Retrieving the relationships among a subset of taxa in these large phylogenies can be a challenging or time-consuming task. Addressing this challenge requires the development of tools that facilitate the easy retrieval of subtrees from any user-spec...
Preprint
Full-text available
Gene regulatory networks (GRNs) drive developmental and cellular differentiation, and variation in their architectures gives rise to morphological diversity. Pioneering studies in Aspergillus fungi, coupled with subsequent work in other filamentous fungi, have shown that the GRN governed by the BrlA, AbaA, and WetA proteins controls the development...
Article
Full-text available
Fermented foods provide novel ecological opportunities for natural populations of microbes to evolve through successive recolonization of resource-rich substrates. Comparative genomic data have reconstructed the evolutionary histories of microbes adapted to food environments, but experimental studies directly demonstrating the process of domesticat...
Article
Full-text available
The draft genome of the ascomycete fungus Xylaria flabelliformis (previously known as Xylaria cubensis ) was sequenced using Illumina paired-end technology. The assembled genome is 41.2 Mb long and contains 11,404 genes. This genome will contribute to our understanding of X. flabelliformis secondary metabolism and the organism’s ability to live as...
Article
Full-text available
Variation in synonymous codon usage is abundant across multiple levels of organization: between codons of an amino acid, between genes in a genome, and between genomes of different species. It is now well understood that variation in synonymous codon usage is influenced by mutational bias coupled with both natural selection for translational effici...