12 results on '"Clayton M. Carey"'
Search Results
2. Adaptive duplication and genetic diversification of protein kinase R contribute to the specificity of bat-virus interactions
- Author
-
Stéphanie Jacquet, Michelle Culbertson, Chi Zhang, Adil El Filali, Clément De La Myre Mory, Jean-Baptiste Pons, Ondine Filippi-Codaccioni, M. Elise Lauterbur, Barthélémy Ngoubangoye, Jeanne Duhayer, Clément Verez, Chorong Park, Clara Dahoui, Clayton M. Carey, Greg Brennan, David Enard, Andrea Cimarelli, Stefan Rothenburg, Nels C. Elde, Dominique Pontier, Lucie Etienne, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Vaccine Related ,Rare Diseases ,Infectious Diseases ,Emerging Infectious Diseases ,Multidisciplinary ,Prevention ,Biodefense ,[SDV]Life Sciences [q-bio] ,Genetics ,Small Pox ,Infection ,Biotechnology - Abstract
Several bat species act as asymptomatic reservoirs for many viruses that are highly pathogenic in other mammals. Here, we have characterized the functional diversification of the protein kinase R (PKR), a major antiviral innate defense system. Our data indicate that PKR has evolved under positive selection and has undergone repeated genomic duplications in bats in contrast to all studied mammals that have a single copy of the gene. Functional testing of the relationship between PKR and poxvirus antagonists revealed how an evolutionary conflict with ancient pathogenic poxviruses has shaped a specific bat host-virus interface. We determined that duplicated PKRs of the Myotis species have undergone genetic diversification, allowing them to collectively escape from and enhance the control of DNA and RNA viruses. These findings suggest that viral-driven adaptations in PKR contribute to modern virus-bat interactions and may account for bat-specific immunity.
- Published
- 2022
3. Adaptive duplication and functional diversification of Protein kinase R contribute to the uniqueness of bat-virus interactions
- Author
-
Stéphanie Jacquet, Michelle Culbertson, Chi Zang, Adil El Filali, Clément De La Myre Mory, Jean-Baptiste Pons, Ondine Filippi-Codaccioni, M. Elise Lauterbur, Barthélémy Ngoubangoye, Jeanne Duhayer, Clément Verez, Chorong Park, Clara Dahoui, Clayton M. Carey, Greg Brennan, David Enard, Andrea Cimarelli, Stefan Rothenburg, Nels C. Elde, Dominique Pontier, Lucie Etienne, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
[SDV]Life Sciences [q-bio] ,[SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE] ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity - Abstract
Several bat species act as asymptomatic reservoirs for many viruses that are instead highly pathogenic in other mammals. Here, we have characterized the functional diversification of the Protein kinase R (PKR), a major antiviral innate defense system. Our data indicate that PKR has evolved under positive selection and has undergone repeated genomic duplications in bats, in contrast to all studied mammals that possess a single copy of the gene. Functional testing of the relationship between PKR and poxvirus antagonists revealed how an evolutionary conflict with ancient pathogenic poxviruses has shaped a specific bat host-virus interface. More importantly, we determined that duplicated PKRs of the Myotis species have undergone functional diversification allowing them to collectively escape from and enhance control of DNA and RNA viruses. These findings suggest that viral-driven adaptations in PKR contribute to modern virus-bat interactions and may account for bat specific immunity.
- Published
- 2022
4. Structure of the germline genome of Tetrahymena thermophila and relationship to the massively rearranged somatic genome
- Author
-
Eileen P Hamilton, Aurélie Kapusta, Piroska E Huvos, Shelby L Bidwell, Nikhat Zafar, Haibao Tang, Michalis Hadjithomas, Vivek Krishnakumar, Jonathan H Badger, Elisabet V Caler, Carsten Russ, Qiandong Zeng, Lin Fan, Joshua Z Levin, Terrance Shea, Sarah K Young, Ryan Hegarty, Riza Daza, Sharvari Gujja, Jennifer R Wortman, Bruce W Birren, Chad Nusbaum, Jainy Thomas, Clayton M Carey, Ellen J Pritham, Cédric Feschotte, Tomoko Noto, Kazufumi Mochizuki, Romeo Papazyan, Sean D Taverna, Paul H Dear, Donna M Cassidy-Hanley, Jie Xiong, Wei Miao, Eduardo Orias, and Robert S Coyne
- Subjects
Tetrahymena thermophila ,chromosome breakage ,intermal eliminated sequence ,genome rearrangement ,transposable element ,centromere ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
The germline genome of the binucleated ciliate Tetrahymena thermophila undergoes programmed chromosome breakage and massive DNA elimination to generate the somatic genome. Here, we present a complete sequence assembly of the germline genome and analyze multiple features of its structure and its relationship to the somatic genome, shedding light on the mechanisms of genome rearrangement as well as the evolutionary history of this remarkable germline/soma differentiation. Our results strengthen the notion that a complex, dynamic, and ongoing interplay between mobile DNA elements and the host genome have shaped Tetrahymena chromosome structure, locally and globally. Non-standard outcomes of rearrangement events, including the generation of short-lived somatic chromosomes and excision of DNA interrupting protein-coding regions, may represent novel forms of developmental gene regulation. We also compare Tetrahymena’s germline/soma differentiation to that of other characterized ciliates, illustrating the wide diversity of adaptations that have occurred within this phylum.
- Published
- 2016
- Full Text
- View/download PDF
5. CRISPR Rube Goldberg machines for visualizing cell lineage
- Author
-
Clayton M. Carey and James A. Gagnon
- Subjects
0301 basic medicine ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,General Neuroscience ,CRISPR ,Cell lineage ,Computational biology ,Biology ,Stem cell ,Neuroscience ,030217 neurology & neurosurgery ,Sequence (medicine) - Abstract
A new technique developed by Garcia-Marques and colleagues uses CRISPR–Cas9 editing to activate an ordered sequence of fluorescent markers in stem cells and their progeny. These tools represent a new way to probe the spatial and temporal patterns of cell lineage progression.
- Published
- 2020
6. Conflicts with diarrheal pathogens trigger rapid evolution of an intestinal signaling axis
- Author
-
Michael S. Kay, Sarah E. Apple, Zoe A. Hilbert, Nels C. Elde, and Clayton M. Carey
- Subjects
Genetics ,0303 health sciences ,030306 microbiology ,Transgene ,Guanylin ,Enterotoxin ,Biology ,03 medical and health sciences ,chemistry.chemical_compound ,Diarrhea ,chemistry ,Genetic variation ,medicine ,Secretion ,medicine.symptom ,Receptor ,030304 developmental biology ,Uroguanylin - Abstract
The pathogenesis of infectious diarrheal diseases is largely attributed to enterotoxin proteins that disrupt intestinal water absorption, causing severe dehydration. Despite profound health consequences, the impacts of diarrhea-causing microbes on the evolutionary history of host species are largely unknown. We investigated patterns of genetic variation in mammalian Guanylate Cyclase-C (GC-C), an intestinal receptor frequently targeted by bacterial enterotoxins, to determine how hosts might adapt in response to diarrheal infections. Under normal conditions, GC-C interacts with endogenous guanylin peptides to promote water secretion in the intestine, but signaling can be hijacked by bacterially-encoded heat-stable enterotoxins (STa) during infection, which leads to overstimulation of GC-C and diarrhea. Phylogenetic analysis in mammals revealed evidence of recurrent positive selection in the GC-C ligand-binding domain in primates and bats, consistent with selective pressures to evade interactions with STa. Using in vitro assays and transgenic intestinal organoids to model STa-mediated diarrhea, we show that GC-C diversification in these lineages results in substantial variation in toxin susceptibility. In bats, we observe a unique pattern of compensatory coevolution in the endogenous GC-C ligand uroguanylin, reflecting intense bouts of positive selection at the receptor-ligand interface. These findings demonstrate control of water physiology as a previously unrecognized interface for genetic conflict and reveal diarrheal pathogens as a source of selective pressure among diverse mammals.
- Published
- 2020
- Full Text
- View/download PDF
7. Diarrheal pathogens trigger rapid evolution of the guanylate cyclase-C signaling axis in bats
- Author
-
Nels C. Elde, Sarah E. Apple, Clayton M. Carey, Michael S. Kay, and Zoe A. Hilbert
- Subjects
Diarrhea ,Sodium-Hydrogen Exchangers ,Bacterial Toxins ,Cystic Fibrosis Transmembrane Conductance Regulator ,Receptors, Enterotoxin ,Cyclic GMP-Dependent Protein Kinase Type II ,Enterotoxin ,Biology ,Microbiology ,Article ,Pathogenesis ,Enterotoxins ,chemistry.chemical_compound ,Chiroptera ,Virology ,Genetic variation ,Animals ,Enterotoxigenic Escherichia coli ,Natriuretic Peptides ,Receptor ,Cyclic GMP ,Vibrio cholerae ,Genetics ,Phylogenetic tree ,Host (biology) ,biology.organism_classification ,Enterocytes ,chemistry ,Guanylate Cyclase ,Parasitology ,Bacteria ,Protein Binding ,Signal Transduction ,Uroguanylin - Abstract
The pathogenesis of infectious diarrheal diseases is largely attributed to enterotoxins that cause dehydration by disrupting intestinal water absorption. We investigated patterns of genetic variation in mammalian guanylate cyclase-C (GC-C), an intestinal receptor targeted by bacterially encoded heat-stable enterotoxins (STa), to determine how host species adapt in response to diarrheal infections. Our phylogenetic and functional analysis of GC-C supports long-standing evolutionary conflict with diarrheal bacteria in primates and bats, with highly variable susceptibility to STa across species. In bats, we further show that GC-C diversification has sparked compensatory mutations in the endogenous uroguanylin ligand, suggesting an unusual scenario of pathogen-driven evolution of an entire signaling axis. Together, these findings suggest that conflicts with diarrheal pathogens have had far-reaching impacts on the evolution of mammalian gut physiology.
- Published
- 2021
8. Endless Conflicts: Detecting Molecular Arms Races in Mammalian Genomes
- Author
-
Clayton M. Carey, Jacob C Cooper, Nitin Phadnis, Christopher J. Leonard, Aaron R. Quinlan, Nels C. Elde, and Brent S. Pedersen
- Subjects
Molecular interactions ,Phylogenetic tree ,Evolutionary biology ,Phylogenetics ,Positive selection ,Biology ,Clade ,Gene ,Genome ,Selection (genetic algorithm) - Abstract
Recurrent positive selection at the codon level is often a sign that a gene is engaged in a molecular arms race – a conflict between the genome of its host and the genome of another species over mutually exclusive access to a resource that has a direct effect on the fitness of both individuals. Detecting molecular arms races has led to a better understanding of how evolution changes the molecular interfaces of proteins when organisms compete over time, especially in the realm of host-pathogen interactions. Here, we present a method for detection of gene-level recurrent positive selection across entire genomes for a given phylogenetic group. We deploy this method on five mammalian clades – primates, mice, deer mice, dogs, and bats – to both detect novel instances of recurrent positive selection and to compare the prevalence of recurrent positive selection between clades. We analyze the frequency at which individual genes are targets of recurrent positive selection in multiple clades. We find that coincidence of selection occurs far more frequently than expected by chance, indicating that all clades experience shared selective pressures. Additionally, we highlight Polymeric Immunoglobulin Receptor (PIGR) as a gene which shares specific amino acids under recurrent positive selection in multiple clades, indicating that it has been locked in a molecular arms race for ∼100My. These data provide an in-depth comparison of recurrent positive selection across the mammalian phylogeny, and highlights of the power of comparative evolutionary approaches to generate specific hypotheses about the molecular interactions of rapidly evolving genes.
- Published
- 2019
9. Recurrent loss-of-function mutations reveal costs to OAS1 antiviral activity in primates
- Author
-
Melissa K. Hartley, Apurva A. Govande, Juliane M. Cooper, Clayton M. Carey, Nels C. Elde, and Philip J. Kranzusch
- Subjects
Models, Molecular ,Primates ,Protein Conformation ,RNase P ,Virus Replication ,Antiviral Agents ,Microbiology ,Virus ,Article ,Evolution, Molecular ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Sequence Analysis, Protein ,Virology ,Endoribonucleases ,2',5'-Oligoadenylate Synthetase ,Animals ,Humans ,Ribonuclease ,Amino Acid Sequence ,Cytotoxicity ,Loss function ,RNA, Double-Stranded ,030304 developmental biology ,Genetics ,0303 health sciences ,Oligoribonucleotides ,biology ,Adenine Nucleotides ,030302 biochemistry & molecular biology ,Alternative splicing ,Genetic Variation ,RNA ,Haplorhini ,Cell biology ,RNA silencing ,Viral replication ,Mutation ,Viruses ,biology.protein ,Parasitology ,030217 neurology & neurosurgery ,Ribonuclease L - Abstract
Immune responses counteract infections and can also cause collateral damage to hosts. We investigated functional outcomes of variation in the rapidly evolving antiviral double-stranded RNA (dsRNA) sensing factor Oligoadenylate Synthetase 1 (OAS1) in primates as a model for understanding how individual immune pathways evolve to minimize deleterious effects on host fitness. Upon binding of dsRNAs, OAS1 polymerizes ATP into 2′–5′ linked oligoadenylate (2-5A), which in turn activates Latent Ribonuclease (RNase L) to kill virus infected cells. OAS1 can undergo auto-activation by host encoded RNAs, raising the question of how it might evolve to mitigate RNase L-mediated cytotoxicity. Using a new yeast-based growth assay, we observed a pattern of frequent loss of 2-5A synthesis by OAS1 from several species. In gorillas, we identified a polymorphism in a conserved substrate binding residue that severely decreases catalytic function. In contrast, lowered 2-5A generation previously associated with variation in humans results from production of unstable OAS1 isoforms. Examination of OAS1 function in monkeys revealed a spectrum of activities, including the complete loss of 2-5A synthesis in tamarins. Frequent loss of catalytic activity in primates suggests that costs associated with OAS1 activation can be so detrimental to host fitness that its pathogen-protective effects are repeatedly forfeited.
- Published
- 2018
- Full Text
- View/download PDF
10. Structure of the germline genome of Tetrahymena thermophila and relationship to the massively rearranged somatic genome
- Author
-
Jie Xiong, Riza M. Daza, Robert S. Coyne, Nikhat Zafar, Tomoko Noto, Lin Fan, Eduardo Orias, Eileen P. Hamilton, Cédric Feschotte, Donna Cassidy-Hanley, Jennifer R. Wortman, Michalis Hadjithomas, Piroska Huvos, Wei Miao, Joshua Z. Levin, Jonathan H. Badger, Romeo Papazyan, Jainy Thomas, Vivek Krishnakumar, Clayton M. Carey, Sharvari Gujja, Sarah Young, Qiandong Zeng, Ryan Hegarty, Paul H. Dear, Terrance Shea, Elisabet Caler, Aurélie Kapusta, Chad Nusbaum, Ellen J. Pritham, Haibao Tang, Shelby L. Bidwell, Kazufumi Mochizuki, Bruce W. Birren, Sean D. Taverna, and Carsten Russ
- Subjects
0301 basic medicine ,Genome evolution ,QH301-705.5 ,Science ,Genomics ,Genome ,General Biochemistry, Genetics and Molecular Biology ,Tetrahymena thermophila ,03 medical and health sciences ,Biology (General) ,Genetics ,genome rearrangement ,General Immunology and Microbiology ,biology ,General Neuroscience ,Tetrahymena ,General Medicine ,Genome project ,Gene rearrangement ,transposable element ,biology.organism_classification ,intermal eliminated sequence ,030104 developmental biology ,centromere ,chromosome breakage ,Medicine ,Programmed DNA elimination ,Chromosome breakage - Abstract
The germline genome of the binucleated ciliate Tetrahymena thermophila undergoes programmed chromosome breakage and massive DNA elimination to generate the somatic genome. Here, we present a complete sequence assembly of the germline genome and analyze multiple features of its structure and its relationship to the somatic genome, shedding light on the mechanisms of genome rearrangement as well as the evolutionary history of this remarkable germline/soma differentiation. Our results strengthen the notion that a complex, dynamic, and ongoing interplay between mobile DNA elements and the host genome have shaped Tetrahymena chromosome structure, locally and globally. Non-standard outcomes of rearrangement events, including the generation of short-lived somatic chromosomes and excision of DNA interrupting protein-coding regions, may represent novel forms of developmental gene regulation. We also compare Tetrahymena’s germline/soma differentiation to that of other characterized ciliates, illustrating the wide diversity of adaptations that have occurred within this phylum.
- Published
- 2016
11. Author response: Structure of the germline genome of Tetrahymena thermophila and relationship to the massively rearranged somatic genome
- Author
-
Eduardo Orias, Robert S. Coyne, Vivek Krishnakumar, Piroska Huvos, Elisabet Caler, Kazufumi Mochizuki, Eileen P. Hamilton, Jainy Thomas, Haibao Tang, Shelby L. Bidwell, Aurélie Kapusta, Terrance Shea, Sean D. Taverna, Sharvari Gujja, Michalis Hadjithomas, Jie Xiong, Chad Nusbaum, Clayton M. Carey, Ellen J. Pritham, Wei Miao, Carsten Russ, Nikhat Zafar, Donna Cassidy-Hanley, Cédric Feschotte, Jonathan H. Badger, Bruce W. Birren, Ryan Hegarty, Paul H. Dear, Sarah Young, Romeo Papazyan, Joshua Z. Levin, Tomoko Noto, Riza M. Daza, Lin Fan, Qiandong Zeng, and Jennifer R. Wortman
- Subjects
Genetics ,Somatic cell ,Tetrahymena ,Biology ,biology.organism_classification ,Genome ,Germline - Published
- 2016
12. Recombinant rubistatin (r-Rub), an MVD disintegrin, inhibits cell migration and proliferation, and is a strong apoptotic inducer of the human melanoma cell line SK-Mel-28
- Author
-
Elda E. Sánchez, Raymund Bueno, Julio G. Soto, Daniel A. Gutierrez, Sara Lucena, Clayton M. Carey, and Christopher Petro
- Subjects
Platelet Aggregation ,Disintegrins ,Molecular Sequence Data ,Apoptosis ,Toxicology ,Article ,HeLa ,Cell Movement ,Cell Line, Tumor ,Crotalid Venoms ,Disintegrin ,Animals ,Humans ,Amino Acid Sequence ,Cloning, Molecular ,Peptide sequence ,Cell Proliferation ,Base Sequence ,biology ,Cell growth ,Crotalus ,Cell migration ,Biological activity ,Sequence Analysis, DNA ,biology.organism_classification ,Molecular biology ,Recombinant Proteins ,Cell biology ,Gene Expression Regulation ,Cell culture ,biology.protein ,Oligopeptides ,HeLa Cells - Abstract
Disintegrins are low molecular weight peptides isolated from viper venom. These peptides bind to integrin receptors using a conserved binding motif sequence containing an RGD or similar motif. As a consequence, disintegrins can inhibit platelet aggregation and inhibit cell migration, proliferation, and initiate apoptosis in cancer cell lines. Rubistatin is a MVD disintegrin cloned from a Crotalus ruber ruber venom gland. The biological activity of MVD disintegrins is poorly understood. Recombinant rubistatin (r-Rub) was cloned into a pET32b plasmid and expressed in reductase-deficient Escherichia coli. Expression was induced with IPTG and the resulting fusion peptide was affinity purified, followed by thrombin cleavage, and removal of vector coded sequences. r-Rub peptide inhibited ADP-induced platelet aggregation by 54% ± 6.38 in whole blood. We assessed the ability of r-Rub to initiate apoptosis in three human cancer cell lines. Cultures of SK-Mel-28, HeLA, and T24 cells were grown for 24 h with 2.5 μM r-Rub followed by Hoechst staining. Chromatin fragmentation was observed in treated SK-Mel-28, but not in T24 or HeLA cells. A TUNEL assay revealed that 51.55% ± 5.28 of SK-Mel-28 cells were apoptotic after 18 h of treatment with 3.5 μM of r-Rub. Cell migration and proliferation assays were performed in order to further characterize the biological effects of r-Rub on SK-Mel-28 cells. At 3 μM, r-Rub inhibited cell migration by 44.4% ± 0.5, while at 3.5 μM it was able to inhibit cell proliferation by 83% ± 6.0.
- Published
- 2012
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.