38 Works

Data from: Stoichiometry controls activity of phase-separated clusters of actin signaling proteins

Lindsay B. Case, Xu Zhang, Jonathon A. Ditlev & Michael K. Rosen
Biomolecular condensates concentrate macromolecules into foci without a surrounding membrane. Many condensates appear to form through multivalent interactions that drive liquid-liquid phase separation (LLPS). LLPS increases the specific activity of actin regulatory proteins toward actin assembly by the Arp2/3 complex. We show that this increase occurs because LLPS of the Nephrin–Nck–N-WASP signaling pathway on lipid bilayers increases membrane dwell time of N-WASP and Arp2/3 complex, consequently increasing actin assembly. Dwell time varies with relative stoichiometry...

Data from: Natural selection interacts with recombination to shape the evolution of hybrid genomes

Molly Schumer, Chenling Xu, Daniel L Powell, Arun Durvasula, Laurits Skov, Chris Holland, John C Blazier, Sriram Sankararaman, Peter Andolfatto, Gil G Rosenthal & Molly Przeworski
To investigate the consequences of hybridization between species, we studied three replicate hybrid populations that formed naturally between two swordtail fish species, estimating their fine-scale genetic map and inferring ancestry along the genomes of 690 individuals. In all three populations, ancestry from the “minor” parental species is more common in regions of high recombination and where there is linkage to fewer putative targets of selection. The same patterns are apparent in a reanalysis of human...

Data from: Impaired spatial memory codes in a mouse model of Rett syndrome

Sara E. Kee, Xiang Mou, Huda Y. Zoghbi & Daoyun Ji
The Mecp2+/-mouse model recapitulates many phenotypes of patients with Rett syndrome (RTT), including learning and memory deficits. It is unknown, however, how the disease state alters memory circuit functions in vivoin RTT mice. Here we recorded from hippocampal place cells, which are thought to encode spatial memories, in freely moving RTT mice and littermate controls. We found that place cells in RTT mice are impaired in their experience-dependent increase of spatial information. This impairment is...

Data from: Partitioning the effects of spatial isolation, nest habitat, and individual diet in causing assortative mating within a population of threespine stickleback

Lisa Kathryn Snowberg & Daniel I. Bolnick
Assortative mating is measured as a phenotypic or genotypic correlation between mates. Although biologists typically view assortative mating in terms of mate preference for similar partners, correlations between mates can also arise from phenotypic spatial structure arising from spatial isolation or habitat preferences. Here, we test whether diet-assortative mating within an ecologically variable population of threespine stickleback results from small-scale geographic isolation or microhabitat preference. We find evidence for assortative mating in the form of...

Systematic characterization of wing mechanosensors that monitor airflow and wing deformations

Joseph Fabian, Igor Siwanowicz, Myriam Uhrhan, Masateru Maeda, Richard Bomphrey & Huai-Ti Lin
Animal wings deform during flight in ways that can enhance lift, facilitate flight control, and mitigate damage. Monitoring the structural and aerodynamic state of the wing is challenging because deformations are passive, and the flow fields are unsteady; it requires distributed mechanosensors that respond to local airflow and strain on the wing. Without a complete map of the sensor arrays, it is impossible to model control strategies underpinned by them. Here, we present the first...

Data from: Live-cell single particle imaging reveals the role of RNA polymerase II in histone H2A.Z eviction

Anand Ranjan, Vu Q. Nguyen, Sheng Liu, Jan Wisniewski, Kim Jee Min, Xiaona Tang, Gaku Mizuguchi, Vivian Jou, Timothy J. Nickels, Brian P. English, Qinsi Zheng, Ed Luk, Timothee Lionnet, Luke D. Lavis, Carl Wu & Ejlal Elalaoui
The H2A.Z histone variant, a genome-wide hallmark of permissive chromatin, is enriched near transcription start sites in all eukaryotes. H2A.Z is deposited by the SWR1 chromatin remodeler and evicted by unclear mechanisms. We tracked H2A.Z in living yeast at single-molecule resolution, and found that H2A.Z eviction is dependent on RNA Polymerase II (Pol II) and the Kin28/Cdk7 kinase, which phosphorylates Serine 5 of heptapeptide repeats on the carboxy-terminal domain of the largest Pol II subunit...

Data from: Synchronized excitability in a network enables generation of internal neuronal sequences

Yingxue Wang, Zachary Roth & Eva Pastalkova
Hippocampal place field sequences are supported by sensory cues and network internal mechanisms. In contrast, sharp-wave (SPW) sequences, theta sequences, and episode field sequences are internally generated. The relationship of these sequences to memory is unclear. SPW sequences have been shown to support learning and have been assumed to also support episodic memory. Conversely, we demonstrate these SPW sequences were present in trained rats even after episodic memory was impaired and after other internal sequences...

Data from: Tensor analysis reveals distinct population structure that parallels the different computational roles of areas M1 and V1

Jeffrey S. Seely, Matthew T. Kaufman, Stephen I. Ryu, Krishna V. Shenoy, John P. Cunningham & Mark M. Churchland
Cortical firing rates frequently display elaborate and heterogeneous temporal structure. One often wishes to compute quantitative summaries of such structure—a basic example is the frequency spectrum—and compare with model-based predictions. The advent of large-scale population recordings affords the opportunity to do so in new ways, with the hope of distinguishing between potential explanations for why responses vary with time. We introduce a method that assesses a basic but previously unexplored form of population-level structure: when...

Data from: Birth-and-death evolution of the fatty acyl-CoA reductase (FAR) gene family and diversification of cuticular hydrocarbon synthesis in Drosophila

Cédric Finet, Kailey Slavik, Jian Pu, Sean B. Carroll & Henry Chung
The birth-and-death evolutionary model proposes that some members of a multigene family are phylogenetically stable and persist as a single copy over time whereas other members are phylogenetically unstable and undergo frequent duplication and loss. Functional studies suggest that stable genes are likely to encode essential functions, while rapidly evolving genes reflect phenotypic differences in traits that diverge rapidly among species. One such class of rapidly diverging traits are insect cuticular hydrocarbons (CHCs), which play...

Data from: Convergence and non-convergence in ecological, phenotypic, and genetic divergence across replicate population pairs of lake and stream stickleback

Renaud Kaeuffer, Catherine Lynn Peichel, Daniel I. Bolnick & Andrew P. Hendry
Convergent (or parallel) evolution provides strong evidence for a deterministic role of natural selection: similar phenotypes evolve when independent populations colonize similar environments. In reality, however, independent populations in similar environments always show some differences: some non-convergent evolution is present. It is therefore important to explicitly quantify the convergent and non-convergent aspects of trait variation, and to investigate the ecological and genetic explanations for each. We performed such an analysis for threespine stickleback (Gasterosteus aculeatus)...

Data from: Experimental evolution of Legionella pneumophila in mouse macrophages leads to strains with altered determinants of environmental survival

Alexander W. Ensminger, Yosuf Yassin, Alexander Miron & Ralph R. Isberg
The Gram-negative bacterium, Legionella pneumophila, is a protozoan parasite and accidental intracellular pathogen of humans. We propose a model in which host cycling through multiple protozoan hosts in the environment holds L. pneumophila in a state of evolutionary stasis as a broad host-range pathogen. Using an experimental evolution approach, we tested this hypothesis by restricting L. pneumophila to growth within mouse macrophages for hundreds of generations. Whole-genome resequencing and high-throughput genotyping identified several parallel adaptive...

Inference of nonlinear receptive field subunits with spike-triggered clustering

Nishal Shah, Nora Brackbill, Colleen Rhoades, Alexandra Kling, Georges Goetz, Alan Litke, Alexander Sher, Eero Simoncelli & E.J. Chichilnisky
Responses of sensory neurons are often modeled using a weighted combination of rectified linear subunits. Since these subunits often cannot be measured directly, a flexible method is needed to infer their properties from the responses of downstream neurons. We present a method for maximum likelihood estimation of subunits by soft-clustering spike-triggered stimuli, and demonstrate its effectiveness in visual neurons. Subunits estimated from parasol retinal ganglion cells (RGCs) in macaque retina partitioned the receptive field into...

Data from: Developmental mechanisms of stripe patterns in rodents

Ricardo Mallarino, Corneliu Henegar, Mercedes Mirasierra, Marie Manceau, Carsten Schradin, Mario Vallejo, Slobodan Beronja, Gregory S. Barsh & Hopi E. Hoekstra
Mammalian colour patterns are among the most recognizable characteristics found in nature and can have a profound impact on fitness. However, little is known about the mechanisms underlying the formation and subsequent evolution of these patterns. Here we show that, in the African striped mouse (Rhabdomys pumilio), periodic dorsal stripes result from underlying differences in melanocyte maturation, which give rise to spatial variation in hair colour. We identify the transcription factor ALX3 as a regulator...

Data from: Molecular, spatial and functional single-cell profiling of the hypothalamic preoptic region

Jeffrey R. Moffitt, Dhananjay Bambah-Mukku, Stephen W. Eichhorn, Eric Vaughn, Karthik Shekhar, Julio D. Perez, Nimrod D. Rubinstein, Junjie Hao, Aviv Regev, Catherine Dulac & Xiaowei Zhuang
The hypothalamus controls essential social behaviors and homeostatic functions. However, the cellular architecture of hypothalamic nuclei, including the molecular identity, spatial organization, and function of distinct cell types, is poorly understood. Here, we developed an imaging-based cell type identification and mapping method and combined it with single-cell RNA-sequencing to create a molecularly annotated and spatially resolved cell atlas of the mouse hypothalamic preoptic region. We profiled ~1 million cells, identified ~70 neuronal populations characterized by...

Data from: Identification of a transporter complex responsible for the cytosolic entry of nitrogen-containing-bisphosphonates

Zhou Yu, Lauren E. Surface, Chong Yon Park, Max A Horlbeck, Gregory A Wyant, Monther Abu-Remaileh, Timothy R. Peterson, David M. Sabatini, Jonathan S. Weissman & Erin K. O'Shea
Nitrogen-containing-bisphosphonates (N-BPs) are widely prescribed to treat osteoporosis and other bone-related diseases. Although previous studies established that N-BPs function by inhibiting the mevalonate pathway in osteoclasts, the mechanism by which N-BPs enter the cytosol from the extracellular space to reach their molecular target is not understood. Here we implemented a CRISPRi-mediated genome-wide screen and identified SLC37A3 (solute carrier family 37 member A3) as a gene required for the action of N-BPs in mammalian cells. We...

Data from: A genetic signature of the evolution of loss of flight in the Galapagos cormorant

Alejandro Burga, Wang Weiguang, Eyal Ben-David, Paul C. Wolf, Andrew M. Ramey, Claudio Verdugo, Karen Lyons, Patricia G. Parker & Leonid Kruglyak
We have a limited understanding of the genetic and molecular basis of evolutionary changes in the size and proportion of limbs. We studied wing and pectoral skeleton reduction leading to flightlessness in the Galapagos cormorant (Phalacrocorax harrisi). We sequenced and de novo assembled the genomes of four cormorant species and applied a predictive and comparative genomics approach to find candidate variants that may have contributed to the evolution of flightlessness. These analyses and cross-species experiments...

Data from: Nuclear microenvironments modulate transcription from low-affinity enhancers

Albert Tsai, Anand K. Muthusamy, Mariana R. P. Alves, Luke D. Lavis, Robert H. Singer, David L. Stern, Justin Crocker & Mariana RP Alves
Transcription factors bind low-affinity DNA sequences for only short durations. It is not clear how brief, low-affinity interactions can drive efficient transcription. Here we report that the transcription factor Ultrabithorax (Ubx) utilizes low-affinity binding sites in the Drosophila melanogaster shavenbaby (svb) locus and related enhancers in nuclear microenvironments of high Ubx concentrations. Related enhancers colocalize to the same microenvironments independently of their chromosomal location, suggesting that microenvironments are highly differentiated transcription domains. Manipulating the affinity...

Data from: The kinetochore prevents centromere-proximal crossover recombination during meiosis

Nadine Vincenten, Lisa-Marie Kuhl, Isabel Lam, Ashwini Oke, Alastair R. W. Kerr, Andreas Hochwagen, Jennifer C. Fung, Scott Keeney, Gerben Vader & Adèle L. Marston
During meiosis, crossover recombination is essential to link homologous chromosomes and drive 22 faithful chromosome segregation. Crossover recombination is non-random across the genome, 23 and centromere-proximal crossovers are associated with an increased risk of aneuploidy, 24 including Trisomy 21 in humans. Here, we identify the conserved Ctf19/CCAN kinetochore sub- 25 complex as a major factor that minimizes potentially deleterious centromere-proximal crossovers 26 in budding yeast. We uncover multi-layered suppression of pericentromeric recombination by the 27...

Genomic changes underlying repeated niche shifts in an adaptive radiation

David A. Marques, Felicity C. Jones, Federica Di Palma, David M. Kingsley & Thomas E. Reimchen
In adaptive radiations, single lineages rapidly diversify by adapting to many new niches. Little is known yet about the genomic mechanisms involved, i.e. the source of genetic variation or genomic architecture facilitating or constraining adaptive radiation. Here, we investigate genomic changes associated with repeated invasion of many different freshwater niches by threespine stickleback in the Haida Gwaii archipelago, Canada, by re-sequencing single genomes from one marine and 28 freshwater populations. We find 89 likely targets...

Data from: Engineering ER-stress dependent non-conventional mRNA splicing

Weihan Li, Voytek Okreglak, Jirka Peschek, Philipp Kimmig, Meghan Zubradt, Jonathan S. Weissman & Peter Walter
The endoplasmic reticulum (ER) protein folding capacity is balanced with the protein folding burden to prevent accumulation of un- or misfolded proteins. The ER membrane-resident kinase/RNase Ire1 maintains ER protein homeostasis through two fundamentally distinct processes. First, Ire1 can initiate a transcriptional response through a non-conventional mRNA splicing reaction to increase the ER folding capacity. Second, Ire1 can decrease the ER folding burden through selective mRNA decay. In Saccharomyces cerevisiae and Schizosaccharomyces pombe, the two...

Data supplement for: Disrupting cortico-cerebellar communication impairs dexterity

Britton Sauerbrei, Jian-Zhong Guo, Jeremy Cohen, Matteo Mischiati, Austin Graves, Ferruccio Pisanello, Kristin Branson & Adam Hantman
This dataset, along with the corresponding code, is a supplement to “Disrupting cortico-cerebellar communication impairs dexterity” (Guo*, Sauerbrei* et al., eLife 2021). It consists of single-unit electrophysiology data from the pontine nuclei, Purkinje cells, cerebellar nuclei, and motor cortex of awake mice, along with measurements of the hand position of mice performing reaching movements. These data address the question of how the dynamics of motor cortex and cerebellum interact to control skilled reaching. First, we...

Conserved structural elements specialize ATAD1 as a membrane protein extraction machine

Lan Wang, Hannah Toutkoushian, Vladislav Belyy, Claire Kokontis & Peter Walter
The mitochondrial AAA protein ATAD1 (in humans; Msp1 in yeast) removes mislocalized membrane proteins, as well as stuck import substrates from the mitochondrial outer membrane, facilitating their re-insertion into their cognate organelles and maintaining mitochondria’s protein import capacity. In doing so, it helps to maintain proteostasis in mitochondria. How ATAD1 tackles the energetic challenge to extract hydrophobic membrane proteins from the lipid bilayer and what structural features adapt ATAD1 for its particular function has remained...

A dominant-negative SOX18 mutant disrupts multiple regulatory layers essential to transcription factor activity

Jieqiong Lou, Alex McCann, Mehdi Moustaqil, Matthew Graus, Ailisa Blum, Frank Fontaine, Hui Liu, Winnie Luu, Peter Koopman, Emma Sierecki, Yann Gambin, Frédéric Meunier, Zhe Liu, Elizabeth Hinde & Mathias Francois
Few genetically dominant mutations involved in human disease have been fully explained at the molecular level. In cases where the mutant gene encodes a transcription factor, the dominant-negative mode of action of the mutant protein is particularly poorly understood. Here, we studied the genome-wide mechanism underlying a dominant-negative form of the SOX18 transcription factor (SOX18RaOp) responsible for both the classical mouse mutant Ragged Opossum and the human genetic disorder Hypotrichosis-Lymphedema-Telangiectasia-Renal Syndrome. Combining three single-molecule imaging...

Pinpointing the neural signatures of single-exposure visual recognition memory

Vahid Mehrpour, Travis Meyer, Eero P. Simoncelli & Nicole C. Rust
Memories of the images that we have seen are thought to be reflected in the reduction of neural responses in high-level visual areas such as inferotemporal (IT) cortex, a phenomenon known as repetition suppression (RS). We challenged this hypothesis with a task that required rhesus monkeys to report whether images were novel or repeated while ignoring variations in contrast, a stimulus attribute that is also known to modulate the overall IT response. The monkeys’ behavior...

Data from: Gene flow mediates the role of sex chromosome meiotic drive during complex speciation

Colin D. Meiklejohn, Emily L. Landeen, Kathleen E. Gordon, Thomas Rzatkiewicz, Sarah B. Kingan, Anthony J. Geneva, Jeffrey P. Vedanayagam, Christina A. Muirhead, Daniel Garrigan, David L. Stern & Daven C. Presgraves
During speciation, sex chromosomes often accumulate interspecific genetic incompatibilities faster than the rest of the genome. The drive theory posits that sex chromosomes are susceptible to recurrent bouts of meiotic drive and suppression, causing the evolutionary build-up of divergent cryptic sex-linked drive systems and, incidentally, genetic incompatibilities. To assess the role of drive during speciation, we combine high-resolution genetic mapping of X-linked hybrid male sterility with population genomics analyses of divergence and recent gene flow...

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