A5079773342- Evolution and Genetic Dynamics
- Gene Regulatory Network Analysis
- Fungal and yeast genetics research
- Bioinformatics and Genomic Networks
- Plant Virus Research Studies
- Genomics and Phylogenetic Studies
- Single-cell and spatial transcriptomics
- Genetics, Bioinformatics, and Biomedical Research
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Genetic diversity and population structure
- Genetic Mapping and Diversity in Plants and Animals
- Genetics and Physical Performance
- Endoplasmic Reticulum Stress and Disease
- Biomedical Text Mining and Ontologies
- Bacteriophages and microbial interactions
- vaccines and immunoinformatics approaches
- Microbial infections and disease research
- Biotin and Related Studies
- Adipose Tissue and Metabolism
- Heat shock proteins research
- Esophageal and GI Pathology
- Protist diversity and phylogeny
- Prenatal Screening and Diagnostics
- Morphological variations and asymmetry
Arizona State University
2019-2025
University of Pennsylvania
2024
Stanford University
2016-2020
New York University
2013-2020
National Human Genome Research Institute
2012
National Institutes of Health
2012
University of California, Santa Barbara
2011
Harvard University Press
2011
Harvard University
2010
Center for Systems Biology
2010
We describe the draft genome of microcrustacean Daphnia pulex, which is only 200 megabases and contains at least 30,907 genes. The high gene count a consequence an elevated rate duplication resulting in tandem clusters. More than third Daphnia's genes have no detectable homologs any other available proteome, most amplified families are specific to lineage. coexpansion interacting within metabolic pathways suggests that maintenance duplicated not random, analysis expression under different...
Evolving lineages face a constant intracellular threat: most new coding sequence mutations destabilize the folding of encoded protein. Misfolded proteins form insoluble aggregates and are hypothesized to be intrinsically cytotoxic. Here, we experimentally isolate fitness cost caused by toxicity misfolded proteins. We exclude other costs protein misfolding, such as loss functional or attenuation growth-limiting synthesis resources, comparing growth rates budding yeast expressing folded...
Building a genotype-phenotype-fitness map of adaptation is central goal in evolutionary biology. It difficult even when adaptive mutations are known because it hard to enumerate which phenotypes make these adaptive. We address this problem by first quantifying how the fitness hundreds yeast mutants responds subtle environmental shifts. then model number collectively influence decomposing patterns variation. find that small inferred can predict near their original glucose-limited evolution...
The protein-folding chaperone Hsp90 has been proposed to buffer the phenotypic effects of mutations. potential for and other putative buffers increase robustness mutation had major impact on disease models, quantitative genetics, evolutionary theory. But sometimes contradicts expectations a by potentiating rapid changes that would otherwise not occur. Here, we quantify Hsp90's ability or potentiate (i.e., diminish enhance) genetic variation single-cell morphological features in budding...
The phrase "survival of the fittest" has become an iconic descriptor how natural selection works. And yet, precisely measuring fitness, even for single-celled microbial populations growing in controlled laboratory conditions, remains a challenge. While numerous methods exist to perform these measurements, including recently developed utilizing DNA barcodes, all are limited their precision differentiate strains with small fitness differences. In this study, we rule out some major sources...
Abstract Yeasts are naturally diverse, genetically tractable, and easy to grow such that researchers can investigate any number of genotypes, environments, or interactions thereof. However, studies yeast transcriptomes have been limited by the processing capabilities traditional RNA sequencing techniques. Here we optimize a powerful, high‐throughput single‐cell (scRNAseq) platform, SPLiT‐seq (Split Pool Ligation‐based Transcriptome sequencing), for yeasts apply it 43,388 cells multiple...
Abstract Background Neural tube defects (NTDs) are common birth (~1 in 1000 pregnancies the US and Europe) that have complex origins, including environmental genetic factors. A low level of maternal folate is one well-established risk factor, with periconceptional folic acid supplementation reducing occurrence NTD by 50-70%. Gene variants metabolic pathway (e.g., MTHFR rs1801133 (677 C > T) MTHFD1 rs2236225 (R653Q)) been found to increase risk. We hypothesized additional folate/B12 genes...
Pleiotropy-when a single mutation affects multiple traits-is controversial topic with far-reaching implications. Pleiotropy plays central role in debates about how complex traits evolve and whether biological systems are modular or organized such that every gene has the potential to affect many traits. is also critical initiatives evolutionary medicine seek trap infectious microbes tumors by selecting for mutations encourage growth some conditions at expense of others. Research these fields,...
There is growing interest in designing multidrug therapies that leverage tradeoffs to combat resistance. Tradeoffs are common evolution and occur when, for example, resistance one drug results sensitivity another. Major questions remain about the extent which reliable, specifically, whether mutants provide a given all suffer similar tradeoffs. This question difficult because drug-resistant observed clinic, even those evolved controlled laboratory settings, often biased towards large fitness...
There is growing interest in designing multidrug therapies that leverage tradeoffs to combat resistance. Tradeoffs are common evolution and occur when, for example, resistance one drug results sensitivity another. Major questions remain about the extent which reliable, specifically, whether mutants provide a given all suffer similar tradeoffs. This question difficult because drug-resistant observed clinic, even those evolved controlled laboratory settings, often biased towards large fitness...
Over recent decades, studies of cell-to-cell heterogeneity have shown that meaningful variation in stress responses is an evolved trait, exemplified by bet hedging. Here, we expand upon this work using a high-throughput single-cell transcriptomics approach S. cerevisiae to study responses. We measured individual transcriptional profiles over ten thousand cells subjected two types stress: protein misfolding (an intrinsic stress) and nutrient deprivation extrinsic stress). Doing so, saw...
Here, we introduce intracellular genomic amplification (INgen), a method that harnesses the cell membrane as natural reaction chamber for DNA amplification, enabling downstream sequencing and sorting. Unlike traditional single-cell techniques, INgen utilizes strand-displacing, isothermal polymerase to amplify within fixed, permeabilized cells while maintaining cell's structural integrity. This approach overcomes challenges associated with both typical hindrances encountered when previously...
There is growing interest in designing multidrug therapies that leverage tradeoffs to combat resistance. Tradeoffs are common evolution and occur when, for example, resistance one drug results sensitivity another. Major questions remain about the extent which reliable, specifically, whether mutants provide a given all suffer similar tradeoffs. This question difficult because drug-resistant observed clinic, even those evolved controlled laboratory settings, often biased towards large fitness...
Across species and environments, the ribosome content of cell populations correlates with population growth rate. The robustness universality this correlation have led to its classification as a "growth law." This law has fueled theories about how evolution selects for microbial organisms that maximize their rate based on nutrient availability, it informed models individual cells regulate rates ribosomal content. However, due methodological limitations, rarely been studied at level cells. While
ABSTRACT Yeasts are naturally diverse, genetically tractable, and easy to grow in a myriad of experimental conditions such that researchers have the ability investigate any number genotypes, strains, environments, or interaction thereof. However, studies variation yeast transcriptome been limited by processing capabilities available RNA sequencing techniques. Here we optimize powerful, high-throughput single-cell (scRNAseq) platform for yeasts. This utilizes combinatorial barcoding strategy...
Countless studies monitor the growth rate of microbial populations as a measure fitness. However, an enormous gap separates growth-rate differences measurable in laboratory from those that natural selection can distinguish efficiently. Taking advantage recent discovery transcript and protein levels budding yeast closely track rate, we explore possibility be more sensitively inferred by monitoring proteomic response to growth, rather than itself. We find set proteins whose levels, aggregate,...
SUMMARY Building a genotype-phenotype-fitness map of adaptation is central goal in evolutionary biology. It notoriously difficult even when the adaptive mutations are known because it hard to enumerate which phenotypes make these adaptive. We address this problem by first quantifying how fitness hundreds yeast mutants responds subtle environmental shifts and then modeling number they must collectively influence decomposing patterns variation. find that small predicts near their original...