36 Works

Data from: A public database of memory and naive B-cell receptor sequences

William S. DeWitt, Paul Lindau, Thomas M. Snyder, Anna M. Sherwood, Marissa Vignali, Christopher S. Carlson, Philip D. Greenberg, Natalie Duerkopp, Ryan O. Emerson & Harlan S. Robins
The vast diversity of B-cell receptors (BCR) and secreted antibodies enables the recognition of, and response to, a wide range of epitopes, but this diversity has also limited our understanding of humoral immunity. We present a public database of more than 37 million unique BCR sequences from three healthy adult donors that is many fold deeper than any existing resource, together with a set of online tools designed to facilitate the visualization and analysis of...

Data from: Demographic history of a recent invasion of house mice on the isolated Island of Gough

Melissa M. Gray, Daniel Wegmann, Ryan J. Haasl, Michael A. White, Sofia I. Gabriel, Jeremy B. Searle, Richard J. Cuthbert, Peter G. Ryan & Bret A. Payseur
Island populations provide natural laboratories for studying key contributors to evolutionary change, including natural selection, population size, and the colonization of new environments. The demographic histories of island populations can be reconstructed from patterns of genetic diversity. House mice (Mus musculus) inhabit islands throughout the globe, making them an attractive system for studying island colonization from a genetic perspective. Gough Island, in the central South Atlantic Ocean, is one of the remotest islands in the...

Data from: The early spread and epidemic ignition of HIV-1 in human populations

Nuno R. Faria, Andrew Rambaut, Marc A. Suchard, Guy Baele, Trevor Bedford, Melissa J. Ward, Andrew J. Tatem, João D. Sousa, Nimalan Arinaminpathy, Jacques Pépin, David Posada, Martine Peeters, Oliver P. Pybus & Philippe Lemey
Thirty years after the discovery of HIV-1, the early transmission, dissemination and establishment of the virus in human populations remain unclear. Using statistical approaches applied to HIV-1 sequence data from central Africa, we show that from the 1920s Kinshasa was the focus of early transmission and the source of pre-1960 pandemic viruses elsewhere. Location and dating estimates were validated using the earliest HIV-1 archival sample, also from Kinshasa. The epidemic histories of HIV-1 group M...

Data from: Seasonality in the migration and establishment of H3N2 Influenza lineages with epidemic growth and decline

Daniel Zinder, Trevor Bedford, Edward B. Baskerville, Robert J. Woods, Manojit Roy & Mercedes Pascual
Background: Influenza A/H3N2 has been circulating in humans since 1968, causing considerable morbidity and mortality. Although H3N2 incidence is highly seasonal, how such seasonality contributes to global phylogeographic migration dynamics has not yet been established. In this study, we incorporate time-varying migration rates in a Bayesian MCMC framework. We focus on migration within China and between China and North-America as case studies, then expand the analysis to global communities. Results: Incorporating seasonally varying migration rates...

Data from: A key metabolic gene for recurrent freshwater colonization and radiation in fishes

Asano Ishikawa, Naoki Kabeya, Koki Ikeya, Ryo Kakioka, Jennifer N. Cech, Naoki Osada, Miguel C. Leal, Jun Inoue, Manabu Kume, Atsushi Toyoda, Ayumi Tezuka, Atsushi J. Nagano, Yo Y. Yamasaki, Yuto Suzuki, Tomoyuki Kokita, Hiroshi Takahashi, Kay Lucek, David Marques, Yusuke Takehana, Kiyoshi Naruse, Seiichi Mori, Oscar Monroig, Nemiah Ladd, Carsten J. Schubert, Blake Matthews … & Jun Kitano
Colonization of new ecological niches has triggered large adaptive radiations. Although some lineages have made use of such opportunities, not all do so. The factors causing this variation among lineages are largely unknown. Here, we show that deficiency in docosahexaenoic acid (DHA), an essential ω-3 fatty acid, can constrain freshwater colonization by marine fishes. Our genomic analyses revealed multiple independent duplications of the fatty acid desaturase gene Fads2 in stickleback lineages that subsequently colonized and...

Data from: Sex chromosome turnover contributes to genomic divergence between incipient stickleback species

Kohta Yoshida, Takashi Makino, Katsushi Yamaguchi, Shuji Shigenobu, Mitsuyasu Hasebe, Masakado Kawata, Manabu Kume, Seiichi Mori, Catherine L. Peichel, Atsushi Toyoda, Asao Fujiyama & Jun Kitano
Sex chromosomes turn over rapidly in some taxonomic groups, where closely related species have different sex chromosomes. Although there are many examples of sex chromosome turnover, we know little about the functional roles of sex chromosome turnover in phenotypic diversification and genomic evolution. The sympatric pair of Japanese threespine stickleback (Gasterosteus aculeatus) provides an excellent system to address these questions: the Japan Sea species has a neo-sex chromosome system resulting from a fusion between an...

Data from: Does plasticity enhance or dampen phenotypic parallelism? A test with three lake-stream stickleback pairs.

Krista B. Oke, Mehvish Bukhari, Renaud Kaeuffer, Gregor Rolshausen, Katja Räsänen, Daniel I. Bolnick, Catherine L. Peichel & Andrew P. Hendry
Parallel (and convergent) phenotypic variation is most often studied in the wild, where it is difficult to disentangle genetic versus environmentally-induced effects. As a result, the potential contributions of phenotypic plasticity to parallelism (and non-parallelism) are rarely evaluated in a formal sense. Phenotypic parallelism could be enhanced by plasticity that causes stronger parallelism across populations in the wild than would be expected from genetic differences alone. Phenotypic parallelism could be dampened if site-specific plasticity induced...

Data from: Annotation of pseudogenic gene segments by massively parallel sequencing of rearranged lymphocyte receptor loci

Jared Dean, Ryan O. Emerson, Marissa Vignali, Anna M. Sherwood, Mark J. Rieder, Christopher S. Carlson & Harlan Robins
Background: The adaptive immune system generates a remarkable range of antigen-specific T-cell receptors (TCRs), allowing the recognition of a diverse set of antigens. Most of this diversity is encoded in the complementarity determining region 3 (CDR3) of the β chain of the αβ TCR, which is generated by somatic recombination of noncontiguous variable (V), diversity (D), and joining (J) gene segments. Deletion and non-templated insertion of nucleotides at the D-J and V-DJ junctions further increases...

Data from: Extreme heterogeneity of influenza virus infection in single cells

Alistair B. Russell, Cole Trapnell & Jesse D. Bloom
Viral infection can dramatically alter a cell's transcriptome. However, these changes have mostly been studied by bulk measurements on many cells. Here we use single-cell mRNA sequencing to examine the transcriptional consequences of influenza virus infection. We find extremely wide cell-to-cell variation in the productivity of viral transcription - viral transcripts comprise less than a percent of total mRNA in many infected cells, but a few cells derive over half their mRNA from virus. Some...

Data from: Defining the alloreactive T cell repertoire using high-throughput sequencing of mixed lymphocyte reaction culture

Ryan O. Emerson, James M. Mathew, Iwona M. Konieczna, Harlan S. Robins & Joseph R. Leventhal
The cellular immune response is the most important mediator of allograft rejection and is a major barrier to transplant tolerance. Delineation of the depth and breadth of the alloreactive T cell repertoire and subsequent application of the technology to the clinic may improve patient outcomes. As a first step toward this, we have used MLR and high-throughput sequencing to characterize the alloreactive T cell repertoire in healthy adults at baseline and 3 months later. Our...

Data from: Arabidopsis hybrid speciation processes

Roswitha Schmickl & Marcus A. Koch
The genus Arabidopsis provides a unique opportunity to study fundamental biological questions in plant sciences utilizing the diploid model species A. thaliana and A. lyrata. However, only a few studies have focused on introgression and hybrid speciation in Arabidopsis, although polyploidy is a common phenomenon within this genus. More recently, there is growing evidence of significant gene flow between the various Arabidopsis species. So far, we know A. suecica and A. kamchatica as fully stabilized...

Data from: Admixture mapping of male nuptial color and body shape in a recently formed hybrid population of threespine stickleback

Tiffany B. Malek, Janette W. Boughman, Ian Dworkin & Catherine L. Peichel
Despite recent progress, we still know relatively little about the genetic architecture that underlies adaptation to divergent environments. Determining whether the genetic architecture of phenotypic adaptation follows any predictable patterns requires data from a wide variety of species. However, in many organisms, genetic studies are hindered by the inability to perform genetic crosses in the laboratory or by long generation times. Admixture mapping is an approach that circumvents these issues by taking advantage of hybridization...

Data from: Adaptive evolution and environmental durability jointly structure phylodynamic patterns in avian influenza viruses

Benjamin Roche, John M. Drake, Justin Brown, David E. Stallknecht, Trevor Bedford & Pejman Rohani
Avian influenza viruses (AIVs) have been pivotal to the origination of human pandemic strains. Despite their scientific and public health significance, however, there remains much to be understood about the ecology and evolution of AIVs in wild birds, where major pools of genetic diversity are generated and maintained. Here, we present comparative phylodynamic analyses of human and AIVs in North America, demonstrating (i) significantly higher standing genetic diversity and (ii) phylogenetic trees with a weaker...

Data from: Caenorhabditis elegans genes affecting interindividual variation in life-span biomarker gene expression

Alexander Mendenhall, Matthew M. Crane, Patricia M. Tedesco, Thomas E. Johnson & Roger Brent
Genetically identical organisms grown in homogenous environments differ in quantitative phenotypes. Differences in one such trait, expression of a single biomarker gene, can identify isogenic cells or organisms that later manifest different fates. For example, in isogenic populations of young adult Caenorhabditis elegans, differences in Green Fluorescent Protein (GFP) expressed from the hsp-16.2 promoter predict differences in life span. Thus, it is of interest to determine how interindividual differences in biomarker gene expression arise. Prior...

Application of simultaneous selective pressures slows adaptation

Lauren Merlo, Kathleen Sprouffske, Taylor Howard, Kristin Gardiner, Aleah Caulin, Steven Blum, Perry Evans, Antonio Bedalov, Paul Sniegowski & Carlo Maley
Background and objectives: Beneficial mutations that arise in an evolving asexual population may compete or interact in ways that alter the overall rate of adaptation through mechanisms such as clonal or functional interference. The application of multiple selective pressures simultaneously may allow for a greater number of adaptive mutations, increasing the opportunities for competition between selectively advantageous alterations, and thereby reducing the rate of adaptation. Methodology: We evolved a strain of Saccharomyces cerevisiae that could...

Data from: Purifying selection maintains dosage-sensitive genes during degeneration of the threespine stickleback Y chromosome

Michael A. White, Jun Kitano & Catherine L. Peichel
Sex chromosomes are subject to unique evolutionary forces that cause suppression of recombination, leading to sequence degeneration and the formation of heteromorphic chromosome pairs (i.e., XY or ZW). Although progress has been made in characterizing the outcomes of these evolutionary processes on vertebrate sex chromosomes, it is still unclear how recombination suppression and sequence divergence typically occur and how gene dosage imbalances are resolved in the heterogametic sex. The threespine stickleback fish (Gasterosteus aculeatus) is...

Data from: Consistency of VDJ rearrangement and substitution parameters enables accurate B cell receptor sequence annotation

Duncan K. Ralph, & Frederick A. Matsen
VDJ rearrangement and somatic hypermutation work together to produce antibody-coding B cell receptor (BCR) sequences for a remarkable diversity of antigens. It is now possible to sequence these BCRs in high throughput; analysis of these sequences is bringing new insight into how antibodies develop, in particular for broadly-neutralizing antibodies against HIV and influenza. A fundamental step in such sequence analysis is to annotate each base as coming from a specific one of the V, D,...

Data from: Single‐cell profiling screen identifies microtubule‐dependent reduction of variability in signaling

C. Gustavo Pesce, William J. Peria, Stefan Zdraljevic, Daniel Rockwell, Richard C. Yu, Alejandro Colman-Lerner, Roger Brent, Alan Bush & María Victoria Repetto
Populations of isogenic cells often respond coherently to signals, despite differences in protein abundance and cell state. Previously, we uncovered processes in the Saccharomyces cerevisiae pheromone response system (PRS) that reduced cell‐to‐cell variability in signal strength and cellular response. Here, we screened 1,141 non‐essential genes to identify 50 “variability genes”. Most had distinct, separable effects on strength and variability of the PRS, defining these quantities as genetically distinct “axes” of system behavior. Three genes affected...

Data from: Mapping polyclonal HIV-1 antibody responses via next-generation neutralization fingerprinting

Nicole A. Doria-Rose, Han R. Altae-Tran, Ryan S. Roark, Stephen D. Schmidt, Matthew S. Sutton, Mark K. Louder, Gwo-Yu Chuang, Robert T. Bailer, Valerie Cortez, Rui Kong, Krisha McKee, Sijy O'Dell, Felicia Wang, Salim S. Abdool Karim, James M. Binley, Mark Connors, Barton F. Haynes, Malcolm A. Martin, David C. Montefiori, Lynn Morris, Julie Overbaugh, Peter D. Kwong, John R. Mascola, Ivelin S. Georgiev & Sijy O’Dell
Computational neutralization fingerprinting, NFP, is an efficient and accurate method for predicting the epitope specificities of polyclonal antibody responses to HIV-1 infection. Here, we present next-generation NFP algorithms that substantially improve prediction accuracy for individual donors and enable serologic analysis for entire cohorts. Specifically, we developed algorithms for: (a) selection of optimized virus neutralization panels for NFP analysis, (b) estimation of NFP prediction confidence for each serum sample, and (c) identification of sera with potentially...

Data from: The impacts of Wolbachia and the microbiome on mate choice in Drosophila melanogaster

Devin Arbuthnott, Tera C. Levin & Daniel E. L. Promislow
Symbionts and parasites can manipulate their hosts’ reproduction to their own benefit, profoundly influencing patterns of mate choice and evolution of the host population. Wolbachia is one of the most widespread symbionts among arthropods, and one that alters its hosts’ reproduction in diverse and dramatic ways. While we are beginning to appreciate how Wolbachia's extreme manipulations of host reproduction can influence species diversification and reproductive isolation, we understand little about how symbionts and Wolbachia, in...

Phosphotyrosine peptide abundance in control and Cul5-deficient MCF10A cells

Jonathan Cooper
The Cullin 5 RING ligase complex inhibits Src activity and Src-dependent transformation of MCF10A epithelial cells, in part by targeting pY proteins such as pYCas for degradation by the ubiquitin-proteasome system (Teckchandani et al., 2014). Because overexpression of Cas alone did not phenocopy CRL5 inhibition (Teckchandani et al., 2014), we infer that CRL5 down-regulates additional pY proteins that become limiting when Cas is over-expressed. We sought to identify such pY proteins by screening for pY...

Data from: Evolutionary inferences from the analysis of exchangeability

Andrew P. Hendry, Renaud Kaeuffer, Erika Crispo, Catherine Lynn Peichel & Daniel I. Bolnick
Evolutionary inferences are usually based on statistical models that compare mean genotypes and phenotypes (or their frequencies) among populations. An alternative is to use the actual distribution of genotypes and phenotypes to infer the “exchangeability” of individuals among populations. We illustrate this approach by using discriminant functions on principal components to classify individuals among paired lake and stream populations of threespine stickleback in each of six independent watersheds. Classification based on neutral and non-neutral microsatellite...

Data from: Minimizing the average distance to a closest leaf in a phylogenetic tree

, Aaron Gallagher, Connor McCoy, Frederick A. Matsen & Connor O. McCoy
When performing an analysis on a collection of molecular sequences, it can be convenient to reduce the number of sequences under consideration while maintaining some characteristic of a larger collection of sequences. For example, one may wish to select a subset of high-quality sequences that represent the diversity of a larger collection of sequences. One may also wish to specialize a large database of characterized “reference sequences” to a smaller subset that is as close...

Data from: Quantifying MCMC exploration of phylogenetic tree space

Chris Whidden, & Frederick A. Matsen
In order to gain an understanding of the effectiveness of phylogenetic Markov chain Monte Carlo (MCMC), it is important to understand how quickly the empirical distribution of the MCMC converges to the posterior distribution. In this paper we investigate this problem on phylogenetic tree topologies with a metric that is especially well suited to the task: the subtree prune-and-regraft (SPR) metric. This metric directly corresponds to the minimum number of MCMC rearrangements required to move...

Data from: Effective online Bayesian phylogenetics via sequential Monte Carlo with guided proposals

Mathieu Fourment, Brian C. Claywell, Vu Dinh, Connor McCoy, & Aaron E. Darling
Modern infectious disease outbreak surveillance produces continuous streams of sequence data which require phylogenetic analysis as data arrives. Current software packages for Bayesian phylogenetic inference are unable to quickly incorporate new sequences as they become available, making them less useful for dynamically unfolding evolutionary stories. This limitation can be addressed by applying a class of Bayesian statistical inference algorithms called sequential Monte Carlo (SMC) to conduct online inference, wherein new data can be continuously incorporated...

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