Publications by authors named "Nathan Brandt"

Article Synopsis
  • Copy number variants (CNVs) are crucial for genetic variation and evolution, but their formation and effects are not well understood, particularly concerning local genomic sequences.
  • Research indicates that specific genomic features, like long terminal repeats (LTRs) and origins of DNA replication (ARS), influence the rapid formation and adaptive significance of CNVs during evolutionary processes in glutamine-limited environments.
  • Experimental evolution in engineered strains shows that altering these genomic elements affects CNV formation rates and fitness, with a significant portion of CNVs linked to a mechanism called Origin Dependent Inverted Repeat Amplification (ODIRA).
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Meiosis is required for the formation of gametes in all sexually reproducing species and the process is well conserved across the tree of life. However, meiosis is sensitive to a variety of external factors, which can impact chromosome pairing, recombination, and fertility. For example, the optimal temperature for successful meiosis varies between species of plants and animals.

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Meiotic recombination is an evolutionary force that acts by breaking up genomic linkage, increasing the efficacy of selection. Recombination is initiated with a double-strand break which is resolved via a crossover, which involves the reciprocal exchange of genetic material between homologous chromosomes, or a non-crossover, which results in small tracts of non-reciprocal exchange of genetic material. Crossover and non-crossover rates vary between species, populations, individuals, and across the genome.

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FlhDC is a heterohexameric complex that acts as a master regulator of flagellar biosynthesis genes in numerous bacteria. Previous studies have identified a single operon encoding this complex. However, we found that two loci are present throughout , and two additional copies are also present in Paraburkholderia unamae.

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Cell growth and quiescence in eukaryotic cells is controlled by an evolutionarily conserved network of signaling pathways. Signal transduction networks operate to modulate a wide range of cellular processes and physiological properties when cells exit proliferative growth and initiate a quiescent state. How signaling networks function to respond to diverse signals that result in cell cycle exit and establishment of a quiescent state is poorly understood.

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A fundamental assumption, common to the vast majority of high-throughput transcriptome analyses, is that the expression of most genes is unchanged among samples and that total cellular RNA remains constant. As the number of analyzed experimental systems increases however, different independent studies demonstrate that this assumption is often violated. We present a calibration method using RNA spike-ins that allows for the measurement of absolute cellular abundance of RNA molecules.

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Copy number variants (CNVs) are a pervasive source of genetic variation and evolutionary potential, but the dynamics and diversity of CNVs within evolving populations remain unclear. Long-term evolution experiments in chemostats provide an ideal system for studying the molecular processes underlying CNV formation and the temporal dynamics with which they are generated, selected, and maintained. Here, we developed a fluorescent CNV reporter to detect de novo gene amplifications and deletions in individual cells.

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Cellular responses to changing environments frequently involve rapid reprogramming of the transcriptome. Regulated changes in mRNA degradation rates can accelerate reprogramming by clearing or stabilizing extant transcripts. Here, we measured mRNA stability using 4-thiouracil labeling in the budding yeast Saccharomyces cerevisiae during a nitrogen upshift and found that 78 mRNAs are subject to destabilization.

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We studied adaptive evolution of gene expression using long-term experimental evolution of in ammonium-limited chemostats. We found repeated selection for non-synonymous variation in the DNA binding domain of the transcriptional activator, GAT1, which functions with the repressor, DAL80 in an incoherent type-1 feedforward loop (I1-FFL) to control expression of the high affinity ammonium transporter gene, MEP2. Missense mutations in the DNA binding domain of GAT1 reduce its binding to the GATAA consensus sequence.

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Cell growth rate is regulated in response to the abundance and molecular form of essential nutrients. InSaccharomyces cerevisiae(budding yeast), the molecular form of environmental nitrogen is a major determinant of cell growth rate, supporting growth rates that vary at least threefold. Transcriptional control of nitrogen use is mediated in large part by nitrogen catabolite repression (NCR), which results in the repression of specific transcripts in the presence of a preferred nitrogen source that supports a fast growth rate, such as glutamine, that are otherwise expressed in the presence of a nonpreferred nitrogen source, such as proline, which supports a slower growth rate.

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Cells regulate their rate of growth in response to signals from the external world. As the cell grows, diverse cellular processes must be coordinated including macromolecular synthesis, metabolism and ultimately, commitment to the cell division cycle. The chemostat, a method of experimentally controlling cell growth rate, provides a powerful means of systematically studying how growth rate impacts cellular processes - including gene expression and metabolism - and the regulatory networks that control the rate of cell growth.

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An essential property of all cells is the ability to exit from active cell division and persist in a quiescent state. For single-celled microbes this primarily occurs in response to nutrient deprivation. We studied the genetic requirements for survival of Saccharomyces cerevisiae when starved for either of two nutrients: phosphate or leucine.

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Rett syndrome is a neurodevelopmental disorder characterized by cognitive and adaptive regression with autistic features, loss of acquired skills, and stereotypic hand movements that almost exclusively affects females. It is an X-linked dominant disorder, with presumed lethality in males. Nonetheless, there are a few descriptions of males suspected of having Rett syndrome.

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