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David A. Kennedy

Bio: David A. Kennedy is an academic researcher from Pennsylvania State University. The author has contributed to research in topics: Virulence & Population. The author has an hindex of 15, co-authored 34 publications receiving 825 citations. Previous affiliations of David A. Kennedy include University of Chicago & National Institutes of Health.

Papers
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TL;DR: It is shown experimentally that immunization of chickens against Marek's disease virus enhances the fitness of more virulent strains, making it possible for hyperpathogenic strains to transmit.
Abstract: Could some vaccines drive the evolution of more virulent pathogens? Conventional wisdom is that natural selection will remove highly lethal pathogens if host death greatly reduces transmission. Vaccines that keep hosts alive but still allow transmission could thus allow very virulent strains to circulate in a population. Here we show experimentally that immunization of chickens against Marek's disease virus enhances the fitness of more virulent strains, making it possible for hyperpathogenic strains to transmit. Immunity elicited by direct vaccination or by maternal vaccination prolongs host survival but does not prevent infection, viral replication or transmission, thus extending the infectious periods of strains otherwise too lethal to persist. Our data show that anti-disease vaccines that do not prevent transmission can create conditions that promote the emergence of pathogen strains that cause more severe disease in unvaccinated hosts.

297 citations

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TL;DR: This work argues that two key differences between vaccines and drugs explain why vaccines have so far proved more robust against evolution than drugs, and suggests that with careful forethought, it may be possible to identify vaccines at risk of failure even before they are introduced.
Abstract: Why is drug resistance common and vaccine resistance rare? Drugs and vaccines both impose substantial pressure on pathogen populations to evolve resistance and indeed, drug resistance typically emerges soon after the introduction of a drug. But vaccine resistance has only rarely emerged. Using well-established principles of population genetics and evolutionary ecology, we argue that two key differences between vaccines and drugs explain why vaccines have so far proved more robust against evolution than drugs. First, vaccines tend to work prophylactically while drugs tend to work therapeutically. Second, vaccines tend to induce immune responses against multiple targets on a pathogen while drugs tend to target very few. Consequently, pathogen populations generate less variation for vaccine resistance than they do for drug resistance, and selection has fewer opportunities to act on that variation. When vaccine resistance has evolved, these generalities have been violated. With careful forethought, it may be possible to identify vaccines at risk of failure even before they are introduced.

111 citations

Journal ArticleDOI
TL;DR: It is shown that a knockout of this gene leads to increased male–male courtship in D. melanogaster, although it leaves other aspects of mating behavior unchanged.
Abstract: New genes can originate by the combination of sequences from unrelated genes or their duplicates to form a chimeric structure. These chimeric genes often evolve rapidly, suggesting that they undergo adaptive evolution and may therefore be involved in novel phenotypes. Their functions, however, are rarely known. Here, we describe the phenotypic effects of a chimeric gene, sphinx, that has recently evolved in Drosophila melanogaster. We show that a knockout of this gene leads to increased male-male courtship in D. melanogaster, although it leaves other aspects of mating behavior unchanged. Comparative studies of courtship behavior in other closely related Drosophila species suggest that this mutant phenotype of male-male courtship is the ancestral condition because these related species show much higher levels of male-male courtship than D. melanogaster. D. melanogaster therefore seems to have evolved in its courtship behaviors by the recruitment of a new chimeric gene.

84 citations

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TL;DR: It is argued that vaccine resistance is less of a concern than drug resistance because it is less likely to evolve and when it does, it is more harmful to human and animal health and well-being.
Abstract: Vaccines and antimicrobial drugs both impose strong selection for resistance. Yet only drug resistance is a major challenge for 21st century medicine. Why is drug resistance ubiquitous and not vaccine resistance? Part of the answer is that vaccine resistance is far less likely to evolve than drug resistance. But what happens when vaccine resistance does evolve? We review six putative cases. We find that in contrast to drug resistance, vaccine resistance is harder to detect and harder to confirm and that the mechanistic basis is less well understood. Nevertheless, in the cases we examined, the pronounced health benefits associated with vaccination have largely been sustained. Thus, we contend that vaccine resistance is less of a concern than drug resistance because it is less likely to evolve and when it does, it is less harmful to human and animal health and well-being. Studies of pathogen strains that evolve the capacity to replicate and transmit from vaccinated hosts will enhance our ability to develop next-generation vaccines that minimize the risk of harmful pathogen evolution.

76 citations

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TL;DR: In this article, the authors use evolution of virulence theory, along with examples, to identify aquaculture practices that might lead to the evolution of increased pathogen virulence, and identify eight practices common in aquaulture that theory predicts may favor evolution toward higher pathogenvirulence.
Abstract: Infectious diseases are economically detrimental to aquaculture, and with continued expansion and intensification of aquaculture, the importance of managing infectious diseases will likely increase in the future. Here, we use evolution of virulence theory, along with examples, to identify aquaculture practices that might lead to the evolution of increased pathogen virulence. We identify eight practices common in aquaculture that theory predicts may favor evolution toward higher pathogen virulence. Four are related to intensive aquaculture operations, and four others are related specifically to infectious disease control. Our intention is to make aquaculture managers aware of these risks, such that with increased vigilance, they might be able to detect and prevent the emergence and spread of increasingly troublesome pathogen strains in the future.

75 citations


Cited by
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3,734 citations

Journal Article
TL;DR: The methodology proposed automatically adapts to the local structure when simulating paths across this manifold, providing highly efficient convergence and exploration of the target density, and substantial improvements in the time‐normalized effective sample size are reported when compared with alternative sampling approaches.
Abstract: The paper proposes Metropolis adjusted Langevin and Hamiltonian Monte Carlo sampling methods defined on the Riemann manifold to resolve the shortcomings of existing Monte Carlo algorithms when sampling from target densities that may be high dimensional and exhibit strong correlations. The methods provide fully automated adaptation mechanisms that circumvent the costly pilot runs that are required to tune proposal densities for Metropolis-Hastings or indeed Hamiltonian Monte Carlo and Metropolis adjusted Langevin algorithms. This allows for highly efficient sampling even in very high dimensions where different scalings may be required for the transient and stationary phases of the Markov chain. The methodology proposed exploits the Riemann geometry of the parameter space of statistical models and thus automatically adapts to the local structure when simulating paths across this manifold, providing highly efficient convergence and exploration of the target density. The performance of these Riemann manifold Monte Carlo methods is rigorously assessed by performing inference on logistic regression models, log-Gaussian Cox point processes, stochastic volatility models and Bayesian estimation of dynamic systems described by non-linear differential equations. Substantial improvements in the time-normalized effective sample size are reported when compared with alternative sampling approaches. MATLAB code that is available from http://www.ucl.ac.uk/statistics/research/rmhmc allows replication of all the results reported.

1,031 citations

Journal ArticleDOI
TL;DR: The origin and evolution of new genes and their functions in eukaryotes is reviewed, demonstrating that novel genes of the various types significantly impacted the evolution of cellular, physiological, morphological, behavioral, and reproductive phenotypic traits.
Abstract: Ever since the pre-molecular era, the birth of new genes with novel functions has been considered to be a major contributor to adaptive evolutionary innovation. Here, I review the origin and evolution of new genes and their functions in eukaryotes, an area of research that has made rapid progress in the past decade thanks to the genomics revolution. Indeed, recent work has provided initial whole-genome views of the different types of new genes for a large number of different organisms. The array of mechanisms underlying the origin of new genes is compelling, extending way beyond the traditionally well-studied source of gene duplication. Thus, it was shown that novel genes also regularly arose from messenger RNAs of ancestral genes, protein-coding genes metamorphosed into new RNA genes, genomic parasites were co-opted as new genes, and that both protein and RNA genes were composed from scratch (i.e., from previously nonfunctional sequences). These mechanisms then also contributed to the formation of numerous novel chimeric gene structures. Detailed functional investigations uncovered different evolutionary pathways that led to the emergence of novel functions from these newly minted sequences and, with respect to animals, attributed a potentially important role to one specific tissue--the testis--in the process of gene birth. Remarkably, these studies also demonstrated that novel genes of the various types significantly impacted the evolution of cellular, physiological, morphological, behavioral, and reproductive phenotypic traits. Consequently, it is now firmly established that new genes have indeed been major contributors to the origin of adaptive evolutionary novelties.

691 citations

Journal ArticleDOI
TL;DR: The scientific books will also be the best reason to choose, especially for the students, teachers, doctors, businessman, and other professions who are fond of reading.
Abstract: In what case do you like reading so much? What about the type of the complex population dynamics a theoretical empirical synthesis book? The needs to read? Well, everybody has their own reason why should read some books. Mostly, it will relate to their necessity to get knowledge from the book and want to read just to get entertainment. Novels, story book, and other entertaining books become so popular this day. Besides, the scientific books will also be the best reason to choose, especially for the students, teachers, doctors, businessman, and other professions who are fond of reading.

627 citations

01 Jan 1988
TL;DR: In this paper, the authors show the best book to read today, the fish viruses and fish viral diseases that will be the best choice for better reading book and their five times will not spend wasted by reading this website.
Abstract: Give us 5 minutes and we will show you the best book to read today. This is it, the fish viruses and fish viral diseases that will be your best choice for better reading book. Your five times will not spend wasted by reading this website. You can take the book as a source to make better concept. Referring the books that can be situated with your needs is sometime difficult. But here, this is so easy. You can find the best thing of book that you can read.

518 citations