- Evolution and Genetic Dynamics
- Bacteriophages and microbial interactions
- Plant Virus Research Studies
- Evolutionary Game Theory and Cooperation
- RNA and protein synthesis mechanisms
- Mathematical and Theoretical Epidemiology and Ecology Models
- HIV Research and Treatment
- Genetic diversity and population structure
- RNA Research and Splicing
- SARS-CoV-2 and COVID-19 Research
- Genomics and Phylogenetic Studies
- HIV/AIDS drug development and treatment
- Animal Virus Infections Studies
- CRISPR and Genetic Engineering
- Plant and animal studies
- HIV/AIDS Research and Interventions
- Cancer-related molecular mechanisms research
- Peptidase Inhibition and Analysis
- Hepatitis C virus research
- Bacterial Infections and Vaccines
- Viral Infections and Immunology Research
- Bayesian Methods and Mixture Models
- Distributed and Parallel Computing Systems
- Parallel Computing and Optimization Techniques
- Physiological and biochemical adaptations
University of North Carolina at Chapel Hill
2014-2024
St. Joseph Hospital
2022
St. Vincent's HealthCare
2022
University of Houston
2010
AIDS United
2009
Johns Hopkins University Center for AIDS Research
2009
University of Malawi
2008
Flagstaff Medical Center
2007
University of Idaho
2006
University of Colorado Colorado Springs
2002
Abstract Fisher’s geometric model of adaptive evolution argues that should generally result from the substitution many mutations small effect because advantageous be more common than those large effect. However, evidence for both by steps and has been mixed. Here we report supporting results a new experimental test model. We subjected bacteriophage ϕ6 to intensified genetic drift in populations caused viral fitness decline through accumulation deleterious mutation. then propagated mutated...
Natural and experimental systems have failed to universally demonstrate a trade-off between generalism specialism. When does occur it is difficult attribute its cause antagonistic pleiotropy without dissecting the genetic basis of adaptation, few previous experiments provide these data. Here we investigate evolution expanded host range (generalism) in RNA virus phi6, an model system allowing adaptive mutations be readily identified. We isolated 10 spontaneous mutants on each three novel...
Hotter is better a hypothesis of thermal adaptation that posits the rate-depressing effects low temperature on biochemical reactions cannot be overcome by physiological plasticity or genetic adaptation. If so, then genotypes populations adapted to warmer temperatures will have higher maximum growth rates than those temperatures. Here we test hotter measuring reaction norms for intrinsic rate population among an intraspecific collection bacteriophages recently isolated from nature. Consistent...
Although deleterious mutations are believed to play a critical role in evolution, assessing their realized effect has been difficult. A key parameter governing the of is nature epistasis, interaction between mutations. RNA viruses should provide one best systems for investigating epistasis because high mutation rate allows thorough investigation mutational effects and interactions. Nonetheless, previous investigations by S. Crotty co-workers F. Elena have unable detect significant epistasis....
The ability of a virus population to colonize novel host is predicted depend on the equilibrium frequency potential colonists (i.e., genotypes capable infecting host) in source population. In this study, we investigated determinants RNA bacteriophage 6. We isolated 40 spontaneous mutants Pseudomonas syringae and sequenced their attachment genes identify responsible mutations. observed 16 different mutations gene used new statistical approach estimate that 39 additional were missed by our...
Bacteriophage genomic evolution has been largely characterized by rampant, promiscuous horizontal gene transfer involving both homologous and nonhomologous source DNA. This pattern emerged through study of the tailed double-stranded DNA (dsDNA) phages is based upon a sparse sampling enormous diversity these phages. The single-stranded family Microviridae, including phiX174, appear to evolve qualitatively different mechanisms, possibly as result their strictly lytic lifestyle small genome...
Two major goals of laboratory evolution experiments are to integrate from genotype phenotype fitness, and understand the genetic basis adaptation in natural populations. Here we demonstrate that both possible by re-examining outcome a previous experiment which bacteriophage G4 was adapted high temperatures. We quantified evolutionary changes thermal reaction norms--the curves describe effect temperature on growth rate phages--and decomposed into modes biological interest. Our analysis...
The distribution of fitness effects for beneficial mutations is paramount importance in determining the outcome adaptation. It generally assumed that follow an exponential distribution, example, theoretical treatments quantitative genetics, clonal interference, experimental evolution, and adaptation DNA sequences. This assumption has been justified by statistical theory extreme values, because fitnesses conferred should represent samples from right tail distribution. Yet value theory, there...
Objectives: To characterize HIV-1 env compartmentalization between cerebrospinal fluid (CSF) and peripheral blood plasma over all stages of the disease course, to determine relationship extent CSF clinical neurologic status. Design: Paired specimens were collected from 66 HIV-infected patients cross-sectionally representing major relating HIV-associated disease, including primary infection, asymptomatic chronic infection with minor global impairment, immune deficiency dementia. Methods:...
RNA secondary structure plays a central role in the replication and metabolism of all viruses, including retroviruses like HIV-1. However, structures with known function represent only fraction reported for HIV-1NL4-3. One tool to assess importance is examine their conservation over evolutionary time. To this end, we used SHAPE model second primate lentiviral genome, SIVmac239, which shares 50% sequence identity at nucleotide level Only about half paired nucleotides are both genomic RNAs...
Competition for resources has long been viewed as a key agent of divergent selection. Theory holds that populations facing severe intraspecific competition will tend to use wider range resources, possibly even using entirely novel are less in demand. Yet, there have few experimental tests these ideas. Using the bacterial virus (bacteriophage) ϕ 6 model system, we examined whether host promotes evolution resource use. In laboratory, exhibits narrow but readily produces mutants capable...
Neisseria gonorrhoeae lipooligosaccharide (LOS) undergoes antigenic variation at a high rate, and this can be monitored by changes in strain's ability to bind LOS-specific monoclonal antibodies. We report here the cloning identification of gene, lsi-2, that mediate variation. The DNA sequence lsi-2 has been determined for N. 1291, strain expresses high-molecular-mass LOS, derivative strain, RS132L, produces truncated LOS. In parental contains string 12 guanines middle its coding sequence....
Ecological speciation hypotheses claim that assortative mating evolves as a consequence of divergent natural selection for ecologically important traits. Reproductive isolation is expected to be particularly likely evolve by this mechanism in species such phytophagous insects mate the habitats which they eat. We tested expectation monitoring evolution reproductive laboratory populations an RNA virus undergoes genetic exchange only when multiple genotypes coinfect same host. subjected four...
Individual cells of Neisseria gonorrhoeae may express a single lipooligosaccharide (LOS) component on their cell surfaces, or they simultaneously multiple LOS structures. Strain FA19 expresses components that react with monoclonal antibodies (MAbs) 2-1-L8 and 1B2. The genetic locus responsible for this phenotype in was identified by isolating clone is able to impart the ability both molecules strain 1291, expressing only MAb 1B2-reactive LOS. This clone, pCLB1, characterized, gene expression...
Middle East respiratory syndrome coronavirus (MERS-CoV) utilizes dipeptidyl peptidase 4 (DPP4) as an entry receptor. While bat, camel, and human DPP4 support MERS-CoV infection, several orthologs, including mouse, ferret, hamster, guinea pig DPP4, do not. Previous work revealed that glycosylation of mouse plays a role in blocking infection. Here, we tested whether also acts determinant permissivity for DPP4. We found that, while important these additional sequence structural determinants...
Competition for resources is thought to play a critical role in both the origins and maintenance of biodiversity. Although numerous laboratory evolution experiments have confirmed that competition can be key driver adaptive diversification, few demonstrated its resulting diversity. We investigate conditions favour origin alternative generalist specialist resource-use phenotypes within same population. Previously, we hosts among φ6 bacteriophage mixed novel (non-permissive) ancestral...
ABSTRACT Coinfection of the same host cell by multiple viruses may lead to increased competition for limited cellular resources, thus reducing fitness an individual virus. Selection should favor that can limit or prevent coinfection, and it is not surprising many have evolved mechanisms do so. Here we explore whether coinfection in RNA bacteriophage φ6 infects Pseudomonas phaseolicola . We estimated comparing frequency hybrids produced two marked phage strains predicted a mathematical model...
We explore the ability of optimal foraging theory to explain observation among marine bacteriophages that host range appears be negatively correlated with abundance in local environment. modified Charnov's classic diet composition model describe ecological dynamics related generalist and specialist φX174 G4, confirmed phages are ecologically favored only at high densities. Our accurately predicted phage populations laboratory microcosms, but had limited success predicting evolutionary...
Abstract Sex is ubiquitous in the natural world, but nature of its benefits remains controversial. Previous studies have suggested that a major advantage sex ability to eliminate interference between selection on linked mutations, phenomenon known as Hill–Robertson interference. However, those may missed both important advantages and disadvantages sexual reproduction because they did not allow distributions mutational effects interactions (i.e., genetic architecture) evolve. Here we...