A5061240448- Evolution and Genetic Dynamics
- Chromosomal and Genetic Variations
- Genetic diversity and population structure
- Malaria Research and Control
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Mosquito-borne diseases and control
- Plant and animal studies
- Bacterial Genetics and Biotechnology
- Genetic Mapping and Diversity in Plants and Animals
- Insect Resistance and Genetics
- Animal Behavior and Reproduction
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Evolutionary Game Theory and Cooperation
- Genetics, Bioinformatics, and Biomedical Research
- Genomics and Chromatin Dynamics
- Invertebrate Immune Response Mechanisms
- Animal Genetics and Reproduction
- Microbial Metabolic Engineering and Bioproduction
- Parasite Biology and Host Interactions
- Insect and Arachnid Ecology and Behavior
- Bacteriophages and microbial interactions
- Neurobiology and Insect Physiology Research
- Bioinformatics and Genomic Networks
Harvard University
2015-2024
Harvard University Press
2001-2024
Broad Institute
2015-2020
ORCID
2020
Northeastern University
2019
Massachusetts Institute of Technology
2017
Evolutionary Genomics (United States)
2003-2014
IIT@Harvard
2014
Institut de Biologia Evolutiva
2013
Fred Hutch Cancer Center
2013
Genetic and Phenotypic Variation.- Organisation of Random Drift.- Mutation the Neutral Theory.- Darwinian Selection.- Inbreeding, Population Subdivision, Migration.- Molecular Genetics.- Evolutionary Quantitative Genomics.- Human Genetics.
Abstract A method is presented for the rapid in vitro amplification of DNA sequences that flank a region known sequence. The uses polymerase chain reaction (PCR), but it has primers oriented reverse direction usual orientation. template restriction fragment been ligated upon itself to form circle. This procedure inverse PCR (IPCR) many applications molecular genetics, example, and identification flanking transposable elements. In this paper we show feasibility IPCR by amplifying an IS1...
Five point mutations in a particular beta-lactamase allele jointly increase bacterial resistance to clinically important antibiotic by factor of approximately 100,000. In principle, evolution this high-resistance might follow any the 120 mutational trajectories linking these alleles. However, we demonstrate that 102 are inaccessible Darwinian selection and many remaining have negligible probabilities realization, because four five fail drug some combinations. Pervasive biophysical pleiotropy...
The mutation process ultimately defines the genetic features of all populations and, hence, has a bearing on wide range issues involving evolutionary genetics, inheritance, and disorders, including predisposition to cancer. Nevertheless, formidable technical barriers have constrained our understanding rate at which mutations arise molecular spectrum their effects. Here, we report use complete-genome sequencing in characterization spontaneously arising yeast Saccharomyces cerevisiae. Our...
Abstract Frequencies of mutant sites are modeled as a Poisson random field in two species that share sufficiently recent common ancestor. The selective effect the new alleles can be favorable, neutral, or detrimental. model is applied to sample configurations nucleotides alcohol dehydrogenase gene (Adh) Drosophila simulans and yakuba. Assuming synonymous mutation rate 1.5 x 10(-8) per site year 10 generations year, we obtain estimates for effective population size (N(e) = 6.5 10(6)),...
Comparison of the gene-expression profiles between adults Drosophila melanogaster and simulans has uncovered evolution genes that exhibit sex-dependent regulation. Approximately half showed differences in expression species, among these, ∼83% involved a gain, loss, increase, decrease, or reversal sex-biased expression. Most interspecific messenger RNA abundance affect male-biased genes. Genes differ species functional clustering only if they were sex-biased. Our results suggest selection may...
Abstract Reduced representation genome‐sequencing approaches based on restriction digestion are enabling large‐scale marker generation and facilitating genomic studies in a wide range of model nonmodel systems. However, sampling chromosomes may introduce bias allele frequency estimation due to polymorphisms sites. To explore the effects this nonrandom its sensitivity different evolutionary parameters, we developed coalescent‐simulation framework mimic biased recovery restriction‐based...
Identifying the properties of gene networks that influence their evolution is a fundamental research goal. However, modes cannot be inferred solely from distribution natural variation, because selection interacts with demography and mutation rates to shape polymorphism divergence. We estimated effects naturally occurring mutations on expression while minimizing effect selection. demonstrate sensitivity increases both increasing trans-mutational target size presence TATA box. Genes greater...
The neutral theory of molecular evolution predicts that the amount polymorphisms within a species will increase proportionally with census population size (Nc). However, this prediction has not been borne out in practice: while range Nc spans many orders magnitude, levels genetic diversity fall comparatively narrow range. Although theoretical arguments have invoked increased efficacy natural selection larger populations to explain discrepancy, few direct empirical tests hypothesis conducted....
Evolving lineages face a constant intracellular threat: most new coding sequence mutations destabilize the folding of encoded protein. Misfolded proteins form insoluble aggregates and are hypothesized to be intrinsically cytotoxic. Here, we experimentally isolate fitness cost caused by toxicity misfolded proteins. We exclude other costs protein misfolding, such as loss functional or attenuation growth-limiting synthesis resources, comparing growth rates budding yeast expressing folded...
The emergence of resistance during multidrug chemotherapy impedes the treatment many human diseases, including malaria, TB, HIV, and cancer. Although certain combination therapies have long been known to be more effective in curing patients than single drugs, impact such treatments on evolution drug is unclear. In particular, very little about how affected by nature interactions--synergy or antagonism--between drugs. Here we directly measure effect various inhibitory subinhibitory...
The spread of high-level pyrimethamine resistance in Africa threatens to curtail the therapeutic lifetime antifolate antimalarials. We studied possible evolutionary pathways evolution using an approach which all mutational intermediates were created by site-directed mutagenesis and assayed for their level drug resistance. coding sequence dihydrofolate reductase (DHFR) from malaria parasite Plasmodium falciparum was mutagenized, tests carried out Escherichia coli under conditions endogenous...
Significance If we could rear genetically identical individuals from a variety of genetic backgrounds and them in the same environment, how much phenotypic variation between genotype would see? Would different differ their degree variability? What account for these differences? We used Drosophila inbred lines to address questions focusing on variability locomotor handedness. show that genotypes vary dramatically propensity variability, itself, as trait, can be heritable, loci affecting...
Significance Traditional methods for estimating malaria transmission based on mosquito sampling are not standardized and unavailable in many countries sub-Saharan Africa. Such studies especially difficult to implement when is low, low the goal of elimination. Malaria-control efforts Senegal have resulted changes population genomics evidenced by increased allele sharing among parasite genomes, often including genomic identity between independently sampled parasites. Fitting an epidemiological...