Publications (44) View all
-
Article: Mosquito Microbiota and Metagenomics, and its Relevance to Disease Transmission
[show abstract] [hide abstract]
ABSTRACT: Application of high throughput sequencing to infer microbial diversity in environmental as well as animal and plant samples is the central theme of metagenomics. This is an immerging area of modern biology that has huge potential to uncover the forms of life we would have never imagined, for example the diversity of microorganisms living within a tiny insect. Metagenomics analyses of disease spreading insects will open up new avenues for better understanding the role of gut microbiota of insect vectors, such as mosquitoes, in ability of these vectors to spread deadly human diseases. The aim of this editorial is to provide the current state of our knowledge on identification of microbial communities in mosquitoes, but more importantly, to give a wakeup call to the vector biology community that it is time to take a good look on the guts of these disease-spreading insects.Biohelikon: Immunity & Diseases. 03/2013; 1(1). -
Article: Nucleotide substitutions in dengue virus serotypes from Asian and American countries: insights into intracodon recombination and purifying selection.
[show abstract] [hide abstract]
ABSTRACT: BACKGROUND: Dengue virus (DENV) infection represents a significant public health problem in many subtropical and tropical countries. Although genetically closely related, the four serotypes of DENV differ in antigenicity for which cross protection among serotypes is limited. It is also believed that both multi-serotype infection as well as the evolution of viral antigenicity may have confounding effects in increased dengue epidemics. Numerous studies have been performed that investigated genetic diversity of DENV, but the precise mechanism(s) of dengue virus evolution are not well understood. RESULTS: We investigated genome-wide genetic diversity and nucleotide substitution patterns in the four serotypes among samples collected from different countries in Asia and Central and South America and sequenced as part of the Genome Sequencing Center for Infectious Diseases' at the Broad Institute. We applied bioinformatics, statistical and coalescent simulation methods to investigate diversity of codon sequences of DENV samples representing the four serotypes. We show that, fixation of nucleotide substitutions is more prominent among the inter-continental isolates (Asian and American) of serotypes 1, 2 and 3 compared to serotype 4 isolates (South and Central America) and are distributed in a non-random manner among the genes encoded by the virus. Nearly one third of the negatively selected sites are associated with fixed mutation sites within serotypes. Our results further show that, of all the sites showing evidence of recombination, the majority (~84%) correspond to sites under purifying selection in the four serotypes. The analysis further shows that genetic recombination occurs within specific codons, albeit with low frequency (< 5% of all recombination sites) throughout the DENV genome of the four serotypes and reveals significant enrichment (p < 0.05) among sites under purifying selection in the virus. CONCLUSION: The study provides the first evidence for intracodon recombination in DENV and suggests that within codon genetic recombination has a significant role in maintaining extensive purifying selection of DENV in natural populations. Our study also suggests that fixation of beneficial mutations may lead to virus evolution via translational selection of specific sites in the DENV genome.BMC Microbiology 02/2013; 13(1):37. · 3.04 Impact Factor -
Article: P53-Mediated Rapid Induction of Apoptosis Conveys Resistance to Viral Infection in Drosophila melanogaster.
[show abstract] [hide abstract]
ABSTRACT: Arthropod-borne pathogens account for millions of deaths each year. Understanding the genetic mechanisms controlling vector susceptibility to pathogens has profound implications for developing novel strategies for controlling insect-transmitted infectious diseases. The fact that many viruses carry genes that have anti-apoptotic activity has long led to the hypothesis that induction of apoptosis could be a fundamental innate immune response. However, the cellular mechanisms mediating the induction of apoptosis following viral infection remained enigmatic, which has prevented experimental verification of the functional significance of apoptosis in limiting viral infection in insects. In addition, studies with cultured insect cells have shown that there is sometimes a lack of apoptosis, or the pro-apoptotic response happens relatively late, thus casting doubt on the functional significance of apoptosis as an innate immunity. Using in vivo mosquito models and the native route of infection, we found that there is a rapid induction of reaper-like pro-apoptotic genes within a few hours following exposure to DNA or RNA viruses. Recapitulating a similar response in Drosophila, we found that this rapid induction of apoptosis requires the function of P53 and is mediated by a stress-responsive regulatory region upstream of reaper. More importantly, we showed that the rapid induction of apoptosis is responsible for preventing the expression of viral genes and blocking the infection. Genetic changes influencing this rapid induction of reaper-like pro-apoptotic genes led to significant differences in susceptibility to viral infection.PLoS Pathogens 02/2013; 9(2):e1003137. · 9.13 Impact Factor -
Article: Codon usage bias: causative factors, quantification methods and genome-wide patterns: with emphasis on insect genomes.
[show abstract] [hide abstract]
ABSTRACT: Codon usage bias refers to the phenomenon where specific codons are used more often than other synonymous codons during translation of genes, the extent of which varies within and among species. Molecular evolutionary investigations suggest that codon bias is manifested as a result of balance between mutational and translational selection of such genes and that this phenomenon is widespread across species and may contribute to genome evolution in a significant manner. With the advent of whole-genome sequencing of numerous species, both prokaryotes and eukaryotes, genome-wide patterns of codon bias are emerging in different organisms. Various factors such as expression level, GC content, recombination rates, RNA stability, codon position, gene length and others (including environmental stress and population size) can influence codon usage bias within and among species. Moreover, there has been a continuous quest towards developing new concepts and tools to measure the extent of codon usage bias of genes. In this review, we outline the fundamental concepts of evolution of the genetic code, discuss various factors that may influence biased usage of synonymous codons and then outline different principles and methods of measurement of codon usage bias. Finally, we discuss selected studies performed using whole-genome sequences of different insect species to show how codon bias patterns vary within and among genomes. We conclude with generalized remarks on specific emerging aspects of codon bias studies and highlight the recent explosion of genome-sequencing efforts on arthropods (such as twelve Drosophila species, species of ants, honeybee, Nasonia and Anopheles mosquitoes as well as the recent launch of a genome-sequencing project involving 5000 insects and other arthropods) that may help us to understand better the evolution of codon bias and its biological significance.Biological Reviews 08/2012; · 9.07 Impact Factor -
Article: Translational selection of genes coding for perfectly conserved proteins among three mosquito vectors.
[show abstract] [hide abstract]
ABSTRACT: The biased usage of synonymous codons affects translational efficiency of genes. We studied codon usage patterns of genes that are perfectly conserved at the amino acid level among three important mosquito vector species: Aedes aegypti (vector of dengue virus), Anopheles gambiae (vector of malaria) and Culex quinquefasciatus (vector of lymphatic filariasis and West Nile Virus). Although these proteins have the same amino acid sequences, non-random usage of synonymous codons is evident among the orthologous genes. The coding sequences of these genes were simulated to generate random mutation sites to be further investigated for patterns of codon bias. It was found that codon usage bias is significantly higher in genes that represented perfectly conserved proteins than genes where variation was apparent at the amino acid sequence. Our results suggest that genes coding for perfectly conserved proteins are highly biased with optimized codons and may be under stringent translational selection in these vector species.Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 06/2012; 12(7):1535-42. · 3.22 Impact Factor
