Understanding how microbial pathogens adapt to treatments, humans and clinical environments is key infer mechanisms of virulence, transmission drug resistance. This may help improve therapies diagnostics for infections with a poor prognosis, such as those caused by fungal pathogens, including Candida. Here we analysed genomic variants across approximately 2,000 isolates from six Candida species (C. glabrata, C. auris, albicans, tropicalis, parapsilosis orthopsilosis) identified genes under...

Fungal infections are a growing medical concern, in part due to increased resistance one or multiple antifungal drugs. However, the evolutionary processes underpinning acquisition of drug poorly understood. Here, we used experimental microevolution study adaptation yeast pathogen Candida glabrata fluconazole and anidulafungin, two widely drugs with different modes action. Our results show widespread ability rapid both Resistance, including multidrug resistance, is often acquired at moderate...

Abstract Structural variants (SVs) underlie genomic variation but are often overlooked due to difficult detection from short reads. Most algorithms have been tested on humans, and it remains unclear how applicable they in other organisms. To solve this, we develop perSVade (personalized structural detection), a sample-tailored pipeline that provides optimally called SVs their inferred accuracy, as well small copy number variants. PerSVade increases SV calling accuracy benchmark of six...

Information that regulates gene expression is encoded throughout each but if different regulatory regions can be understood in isolation, or they interact, unknown. Here we measure mRNA levels for 10,000 open reading frames (ORFs) transcribed from either an inducible constitutive promoter. We find the strength of cotranslational regulation on determined by promoter architecture. By using a novel computational genetic screen 6402 RNA-seq experiments, identify RNA helicase Dbp2 as mechanism...

Oxidative phosphorylation is among the most conserved mitochondrial pathways. However, one of cornerstones this pathway, multi-protein complex NADH : ubiquinone oxidoreductase (complex I) has been lost multiple independent times in diverse eukaryotic lineages. The causes and consequences these convergent losses remain poorly understood. Here, we used a comparative genomics approach to reconstruct evolutionary paths leading I loss infer possible scenarios. By mining available nuclear genomes,...

A synthetic gene circuit for quantifying the strength of native feedback regulation among RNA binding proteins in yeast.

The limited number of available antifungal drugs and the increasing fungal isolates that show drug or multidrug resistance pose a serious medical threat. Several yeast pathogens, such as

Organisms regulate gene expression through changes in the activity of transcription factors (TFs). In yeast, response genes to TF is generally assumed be encoded promoter. To directly test this assumption, we chose 42 and, for each, replaced promoter with a synthetic inducible and measured how protein as function activity. Most exhibited gene-specific dose-response curves not due differences mRNA stability, translation, or stability. Instead, most have an intrinsic ability buffer effects...

Frameshifting errors are common and mRNA quality control pathways, such as nonsense-mediated decay (NMD), exist to degrade these aberrant transcripts. Recent work has shown the existence of a genetic link between NMD codon-usage mediated decay. Here we present computational evidence that pathways synergic for removing frameshifts.

Auto regulatory feedback loops occur in the regulation of molecules ranging from ATP to MAP kinases zinc. Negative can increase a system’s robustness, while positive mediate transitions between cell states. Recent genome-wide experimental and computational studies predict hundreds novel loops. However, not all physical interactions are regulatory, many methods cannot detect self-interactions. Our understanding is therefore hampered by lack high-throughput experimentally quantify presence,...

ABSTRACT Structural variants (SVs) like translocations, deletions, and other rearrangements underlie genetic phenotypic variation. SVs are often overlooked due to difficult detection from short-read sequencing. Most algorithms yield low recall on humans, but the performance in organisms is unclear. Similarly, despite remarkable differences across species’ genomes, most approaches use parameters optimized for humans. To overcome this enable species-tailored approaches, we developed perSVade...

Abstract Information that regulates gene expression is encoded throughout each but if different regulatory regions can be understood in isolation, or they interact, unknown. Here we measure mRNA levels for 10,000 open reading frames (ORFs) transcribed from either an inducible constitutive promoter. We find the strength of co-translational regulation on determined by promoter architecture. Using a novel computational-genetic screen 6402 RNA-seq experiments identify RNA helicase Dbp2 as...

Cells regulate gene expression by changing the concentration and activity of transcription factors (TFs). The response each to changes in TF is generally assumed be encoded promoter. Here we show that, even when promoter itself remains constant, has a unique dose curve. Many genes have an intrinsic ability either buffer or amplify effects high activity. We present coupled mathematical model experimental system for quantifying this property. Promoter buffering can sequences both open reading...

Abstract Living organisms are error-prone. Every second a single human cell produces over 100 transcripts with substitution, frameshift or splicing error. Multiple mRNA quality control pathways exist to degrade these transcripts. Many of involve co-translational regulation stability, such as nonsense mediated decay (NMD) and reduced stability suboptimal codon usage. Recent work has shown the existence genetic link between NMD codon-usage decay. Here we present new computational evidence...