179 Works

Data from: Evolution of mutation rates in hypermutable populations of Escherichia coli propagated at very small effective population size

Tanya Singh, Meredith Hyun & Paul Sniegowski
Mutation is the ultimate source of the genetic variation—including variation for mutation rate itself—that fuels evolution. Natural selection can raise or lower the genomic mutation rate of a population by changing the frequencies of mutation rate modifier alleles associated with beneficial and deleterious mutations. Existing theory and observations suggest that where selection is minimized, rapid systematic evolution of mutation rate either up or down is unlikely. Here, we report systematic evolution of higher and lower...

Data from: Chimpanzees breed with genetically dissimilar mates

Kara K. Walker, Rebecca S. Rudicell, Yingying Li, Beatrice H. Hahn, Emily Wroblewski & Anne E. Pusey
Inbreeding adversely affects fitness, whereas heterozygosity often augments it. Therefore, mechanisms to avoid inbreeding and increase genetic distance between mates should be advantageous in species where adult relatives reside together. Here we investigate mate choice for genetic dissimilarity in chimpanzees, a species in which many females avoid inbreeding through dispersal, but where promiscuous mating and sexual coercion can limit choice when related adults reside together. We take advantage of incomplete female dispersal in Gombe National...

Data from: Gender disparity in physician authorship among commentary articles in high impact medical journals

Mira Mamtani, Frances Shofer, Anita Mudan, Utsha Khatri, Rachael Walker, Jaya Aysola & Jeanmarie Perrone
Background: There is an attrition of women physicians in academic medicine hierarchy. Scholarship in medical journals plays a direct role in career advancement, promotion, and authoritative recognition, and women physician authors are underrepresented in original research articles. Objectives: We sought to determine if women physician authors are similarly underrepresented in commentary articles within high impact journals. Design/Setting/Participants: In this observational study, we abstracted gender, degree, and authorship position from January 1, 2014 to October 16,...

Data from: Nanoaperture fabrication via colloidal lithography for single molecule fluorescence analysis

Shawn H. Pfeil, Kevin Y. Chen, Yale E. Goldman, Shane A. Fiorenza, Ryan M. Jamiolkowski & Alyssa M. Tate
In single molecule fluorescence studies, background emission from labeled substrates often restricts their concentrations to non-physiological nanomolar values. One approach to address this challenge is the use of zero-mode waveguides (ZMWs), nanoscale holes in a thin metal film that physically and optically confine the observation volume allowing much higher concentrations of fluorescent substrates. Standard fabrication of ZMWs utilizes slow and costly E-beam nano-lithography. Herein, ZMWs are made using a self-assembled mask of polystyrene microspheres, enabling...

The soil microbiome increases plant survival and modifies interactions with root endosymbionts in the field

Corlett Wood, Shaniya Markalanda, Connor McFadden & Steven Cassidy
Evidence is accumulating that the soil microbiome—the community of microorganisms living in soils—has a major effect on plant traits and fitness. However, most work to date has taken place under controlled laboratory conditions and has not experimentally disentangled the effect of the soil microbiome on plant performance from the effects of key endosymbiotic constituents. As a result, it is difficult to extrapolate from existing data to understand the role of the soil microbiome in natural...

Isolating human monoclonal antibodies against adeno-associated virus from donors with pre-existing immunity

James Wilson, April R. Giles, Roberto Calcedo & Anna P. Tretiakova
With the advent of single B-cell cloning technology, we can isolate antibodies against virtually any antigen to study the interaction of a given pathogen with the immune system and develop novel therapeutic strategies. Antibodies directed against the capsid of adeno-associated viruses (AAV) are a significant obstacle to effectively leveraging AAV as a gene-delivery vector in seropositive individuals. In order to design next-generation vectors that can evade neutralization by these antibodies, studies have mapped the epitopes...

Hepatic estrogen sulfotransferase distantly sensitizes mice to hemorrhagic shock-induced acute lung injury

Yang Xie, Anne Barbosa, Meishu Xu, Patrick Oberly, Songrong Ren, Robbert Gibbs, Samuel Poloyac, Wenchao Song, Jie Fan & Wen Xie
Hemorrhagic shock (HS) is a potential life-threatening condition that may lead to injury to multiple organs, including the lung. The estrogen sulfotransferase (EST, or SULT1E1) is a conjugating enzyme that sulfonates and deactivates estrogens. In this report, we showed that the expression of Est was markedly induced in the liver, but not in the lung of female mice subject to hemorrhagic shock and resuscitation (HS/R). Genetic ablation or pharmacological inhibition of Est effectively protected female...

Neurofilament light as a biomarker in traumatic brain injury

Pashtun Shahim, Adam Politis, Andre Van Der Merwe, Brian Moore, Yi-Yu Chou, Dzung Pham, John Butman, Ramon Diaz-Arrastia, Jessica Gill, David Brody, Henrik Zetterberg, Kaj Blennow & Leighton Chan
Objective: To determine whether serum neurofilament light (NfL) correlates with CSF NfL, traumatic brain injury (TBI) diagnosis, injury severity, brain volume, and diffusion tensor imaging (DTI) estimates of traumatic axonal injury (TAI). Methods: Participants were prospectively enrolled in Sweden and the United States between 2011 and 2019. The Swedish cohort included 45 hockey players with acute concussion sampled at 6 days, 31 with repetitive concussion with persistent postconcussive symptoms (PCS) assessed with paired CSF and...

Genomic evidence for correlated trait combinations and antagonistic selection contributing to counterintuitive genetic patterns of adaptive diapause divergence in Rhagoletis flies

McCall Calvert, Meredith Doellman, Jeffrey Feder, Glenn Hood, Peter Meyers, Scott Egan, Thomas Powell, Mary Glover, Cheyenne Tait, Hannes Schuler, Stewart Berlocher, James Smith, Patrik Nosil, Dan Hahn & Gregory Ragland
Adaptation to novel environments often results in unanticipated genomic responses to selection. Here, we illustrate how multifarious, correlational selection helps explain a counterintuitive pattern of genetic divergence between the recently derived apple- and ancestral hawthorn-infesting host races of Rhagoletis pomonella (Diptera: Tephritidae). The Apple host race terminate diapause and emerge as adults earlier in the season than the hawthorn host race to coincide with the earlier fruiting phenology of their apple hosts. However, alleles at...

Data from: Unraveling B-lymphocytes in CNS inflammatory diseases: Distinct mechanisms and treatment targets

Bruna Klein Da Costa, Renata Brant De Souza Melo, Giordani Rodrigues Dos Passos, Douglas Gomes Meneses Sevilha Castro, Jefferson Becker, Amit Bar-Or & Douglas Kazutoshi Sato
Specific therapies targeting B lymphocytes in multiple sclerosis (MS) have demonstrated reductions in disease activity and disability progression. Several observational studies have also shown the effects of targeting B lymphocytes in other rare CNS inflammatory diseases, such as neuromyelitis optica spectrum disorder (NMOSD) and autoimmune encephalitis (AE). However, some drugs targeting cytokine receptors involved in B-lymphocyte maturation and proliferation resulted in negative outcomes in MS. These apparently conflicting findings have stimulated research on the pathophysiologic...

Data from: Family network size and survival across the lifespan of female macaques

Lauren J. N. Brent, Angelina Ruiz Lambides & Michael L. Platt
Two decades of research suggest social relationships have a common evolutionary basis in humans and other gregarious mammals. Critical to the support of this idea is growing evidence that mortality is influenced by social integration, but when these effects emerge and how long they last is mostly unknown. Here, we report in adult female macaques that the impact of number of close adult female relatives, a proxy for social integration, on survival is not experienced...

Data from: Clinical factors associated with long-term complete remission versus poor response to chemotherapy in HIV-infected children and adolescents with Kaposi sarcoma receiving bleomycin and vincristine: a retrospective observational study

Nader Kim El-Mallawany, William Kamiyango, Jeremy S. Slone, Jimmy Villiera, Carrie L. Kovarik, Carrie M. Cox, Dirk P. Dittmer, Saeed Ahmed, Gordon E. Schutze, Michael E. Scheurer, Peter N. Kazembe & Parth S. Mehta
Kaposi sarcoma (KS) is the most common HIV-associated malignancy in children and adolescents in Africa. Pediatric KS is distinct from adult disease. We evaluated the clinical characteristics associated with long-term outcomes. We performed a retrospective observational analysis of 70 HIV-infected children and adolescents with KS less than 18 years of age diagnosed between 8/2010 and 6/2013 in Lilongwe, Malawi. Local first-line treatment included bleomycin and vincristine plus nevirapine-based highly active anti-retroviral therapy (HAART). Median age...

Data from: High-throughput sequencing of the T-cell receptor beta chain gene distinguishes two subgroups of cutaneous T-cell lymphoma

Jie Wang, Bryan Rea, Paul Haun, Ryan Emerson, Ilan Kirsch & Adam Bagg
HTS of the TCR beta chain distinguishes two subgroups of CTCLT-cell repertoire characterization data are provided herein as a supplement to: High-Throughput Sequencing of the T-cell receptor beta chain gene distinguishes two subgroups of cutaneous T-cell lymphoma By Jie Wang, MD, Bryan Rea, MD, Paul Haun, MD, Ryan Emerson, PhD, Ilan Kirsch, MD, and Adam Bagg, MD

Data from: Rapid seasonal evolution in innate immunity of wild Drosophila melanogaster

Emily L. Behrman, Virginia M. Howick, Martin Kapun, Fabian Staubach, Alan O. Bergland, Dmitri A. Petrov, Brian P. Lazzaro & Paul S. Schmidt
Understanding the rate of evolutionary change and the genetic architecture that facilitates rapid adaptation is a current challenge in evolutionary biology. Comparative studies show that genes with immune function are among the most rapidly evolving genes across a range of taxa. Here, we use immune defence in natural populations of Drosophila melanogaster to understand the rate of evolution in natural populations and the genetics underlying rapid change. We probed the immune system using the natural...

Data from: Stability of the gorilla microbiome despite simian immunodeficiency virus infection

Andrew H. Moeller, Martine Peeters, Ahidjo Ayouba, Eitel Mpoudi Ngole, Amadine Esteban, Beatrice H. Hahn & Howard Ochman
Simian immunodeficiency viruses (SIVs) have been discovered in over 45 primate species; however, the pathogenic potential of most SIV strains remains unknown due to difficulties inherent in observing wild populations. Because those SIV infections that are pathogenic have been shown to induce changes in the host's gut microbiome, monitoring the microbiota present in faecal samples can provide a noninvasive means for studying the effects of SIV infection on the health of wild-living primates. Here, we...

Data from: Massively parallel multiplex DNA sequencing for specimen identification using an Illumina MiSeq platform

Shadi Shokralla, Teresita M. Porter, Joel F. Gibson, Rafal Dobosz, Daniel H. Janzen, Winnie Hallwachs, G. Brian Golding & Mehrdad Hajibabaei
Genetic information is a valuable component of biosystematics, especially specimen identification through the use of species-specific DNA barcodes. Although many genomics applications have shifted to High-Throughput Sequencing (HTS) or Next-Generation Sequencing (NGS) technologies, sample identification (e.g., via DNA barcoding) is still most often done with Sanger sequencing. Here, we present a scalable double dual-indexing approach using an Illumina Miseq platform to sequence DNA barcode markers. We achieved 97.3% success by using half of an Illumina...

Data from: Secondary contact and local adaptation contribute to genome-wide patterns of clinal variation in Drosophila melanogaster

Alan O. Bergland, Ray Tobler, Josefa Gonzalez, Paul Schmidt, Dimitri A. Petrov & Dmitri Petrov
Populations arrayed along broad latitudinal gradients often show patterns of clinal variation in phenotype and genotype. Such population differentiation can be generated and maintained by both historical demographic events and local adaptation. These evolutionary forces are not mutually exclusive and can in some cases produce nearly identical patterns of genetic differentiation among populations. Here, we investigate the evolutionary forces that generated and maintain clinal variation genome-wide among populations of Drosophila melanogaster sampled in North America...

Data from: Mapping the fitness landscape of gene expression uncovers the cause of antagonism and sign epistasis between adaptive mutations

Hsin-Hung Chou, Nigel F. Delaney, Jeremy A. Draghi & Christopher J. Marx
How do adapting populations navigate the tensions between the costs of gene expression and the benefits of gene products to optimize the levels of many genes at once? Here we combined independently-arising beneficial mutations that altered enzyme levels in the central metabolism of Methylobacterium extorquens to uncover the fitness landscape defined by gene expression levels. We found strong antagonism and sign epistasis between these beneficial mutations. Mutations with the largest individual benefit interacted the most...

Data from: CHIIMP: an automated high-throughput microsatellite genotyping approach reveals greater allelic diversity in wild chimpanzees

Hannah J. Barbian, Andrew Jesse Connell, Alexa N. Avitto, Ronnie M. Russell, Andrew G. Smith, Madhurima S. Gundlapally, Alexander L. Shazad, Yingying Li, Frederic Bibollet-Ruche, Emily E. Wroblewski, Deus Mjungu, Elizabeth V. Lonsdorf, Fiona A. Stewart, Alexander K. Piel, Anne E. Pusey, Paul M. Sharp & Beatrice H. Hahn
Short tandem repeats (STRs), also known as microsatellites, are commonly used to non-invasively genotype wild-living endangered species, including African apes. Until recently, capillary electrophoresis has been the method of choice to determine the length of polymorphic STR loci. However, this technique is labor intensive, difficult to compare across platforms, and notoriously imprecise. Here we developed a MiSeq-based approach and tested its performance using previously genotyped fecal samples from long-term studied chimpanzees in Gombe National Park,...

Data from: Distributed rhythm generators underlie Caenorhabditis elegans forward locomotion

Anthony D Fouad, Shelly Teng, Julian R Mark, Alice Liu, Pilar Alvarez-Illera, Hongfei Ji, Angelica Du, Priya D Bhirgoo, Eli Cornblath, Sihui Asuka Guan & Christopher Fang-Yen
Coordinated rhythmic movements are ubiquitous in animal behavior. In many organisms, chains of neural oscillators underlie the generation of these rhythms. In C. elegans, locomotor wave generation has been poorly understood; in particular, it is unclear where in the circuit rhythms are generated, and whether there exists more than one such generator. We used optogenetic and ablation experiments to probe the nature of rhythm generation in the locomotor circuit. We found that multiple sections of...

Data from: Broad geographic sampling reveals predictable, pervasive, and strong seasonal adaptation in Drosophila

Heather E. Machado, Alan O. Bergland, Ryan Taylor, Susanne Tilk, Emily Behrman, Kelly Dyer, Daniel K. Fabian, Thomas Flatt, Josefa González, Talia L. Karasov, Iryna Kozeretska, Brian P. Lazzaro, Thomas JS Merritt, John E. Pool, Katherine O’Brien, Subhash Rajpurohit, Paula R. Roy, Stephen W. Schaeffer, Svitlana Serga, Paul Schmidt, Dmitri Petrov & Bernard Kim
To advance our understanding of adaptation to temporally varying selection pressures, we identified signatures of seasonal adaptation occurring in parallel among Drosophila melanogaster populations. Specifically, we estimated allele frequencies genome-wide from flies sampled early and late in the growing season from 20 widely dispersed populations. We identified parallel seasonal allele frequency shifts across North America and Europe, demonstrating that seasonal adaptation is a general phenomenon of temperate fly populations. Seasonally fluctuating polymorphisms are enriched at...

Directed Evolution of AAV for Efficient Gene Delivery to Canine and Primate Retina - Raw counts of variants from deep sequencing

Leah Byrne, Timothy Day, Meike Visel, Deniz Dalkara, Valerie Dufour, Felipe Pompeo Marinho, William Merigan, Gustavo Aguirre, William Beltran, David Schaffer & John Flannery
Efficient AAV-mediated gene delivery remains a significant obstacle to effective retinal gene therapies. Here, we apply the process of directed evolution – guided by deep sequencing and followed by direct in vivo secondary selection of high-performing vectors with a GFP-barcoded library – to create AAV viral capsids with new capabilities to deliver genes to the outer retina in large animals. The resulting vectors resulted in efficient targeting of photoreceptors, bipolar cells, and RPE cells in...

Splice altering variant predictions in four archaic hominin genomes

Colin Brand, Laura Colbran & John Anthony Capra
This file contains high-quality autosomal SNVs that occur among four high-coverage archaic genomes aligned to the hg19/GRCh37 reference genome. Each entry corresponds to a single variant with a distinct GENCODE, Human Release 24, annotation per genomic position. Data per variant includes the genomic position, reference/alternate alleles, archaic genotypes, gene annotation, and additional data relevant to the analysis of splicing variants: SpliceAI annotations gene constraint measured using data from gnomAD variant conservation measured using phyloP allele...

Divalent cations bind to phosphoinositides to induce ion and isomer specific propensities for nano-cluster initiation in bilayer membranes

Ravi Radhakrishnan, Ryan Bradley, Paul Janmey & David Slochower
We report all-atom molecular dynamics simulations of physiologically composed asymmetric bilayers containing phosphoinositides in the presence of monovalent and divalent cations. We have characterized the molecular mechanism by which these divalent cations interact with phosphoinositides. Calcium desolvates more readily, consistent with single-molecule calculations, and forms a network of ionic-like bonds that serve as a "molecular glue'' that allows a single ion to coordinate with up to three phosphatidylinositol-(4,5)-bisphosphate lipids. The phosphatidylinositol-(3,5)-bisphosphate isomer shows no such...

Wolbachia-infected ant colonies have increased reproductive investment and an accelerated life cycle

Rohini Singh & Timothy Linksvayer
Wolbachia is a widespread group of maternally-transmitted endosymbiotic bacteria that often manipulates the reproductive strategy and life history of its hosts to favor its own transmission. Wolbachia mediated phenotypic effects are well characterized in solitary hosts, although evidence of similar effects are rare in eusocial insects, such as ants. The invasive pharaoh ant, Monomorium pharaonis, shows natural variation in Wolbachia infection between colonies and can be readily bred under laboratory conditions. We previously showed that...

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