The study also indicates that fixation of specific mutations leads to codon usage bias in dengue virus. One of the interesting findings is that only three amino acids (Leu, Ser and Arg) in the DENV polyprotein are GSI-IX associated with multiple substitutions within codons. Furthermore, the results of this study suggest, for the first time, that intracodon recombination does occur in DENV and is significantly associated with the extent of purifying selection in each serotype. This suggests

that genetic recombination within codons plays an important role in maintaining extensive purifying selection of DENV in PI3K inhibitor natural populations. Authors’ information SKB’s current work focuses on genetic and genomic dissection of dengue susceptibility

of Aedes aegypti vector mosquitoes. He has a broad interest in vector borne diseases with emphasis on vector-virus interactions, disease ecology and evolution and vector competence of disease transmission. He works as a Research Assistant Professor in the Department of Biological Sciences and the Eck Institute for Global Health at the University of Notre Dame, Indiana. DWS’s research is broadly focused on mosquito genetics and genomics. His work primarily concerns genetic analysis of mosquito vector competence to various pathogens as well as on development and application of molecular tools to investigate population biology of see more mosquitoes. He is a Professor of Biological Sciences and the Director of the Eck Institute for Global Health at the University of Notre Dame, Indiana. Acknowledgements We are thankful to Dr. Mathew Henn, Broad Institute of MIT & Harvard, Cambridge for allowing us to use the GRID data and Dr. Mabel Berois for critical reading of the manuscript. This work was supported in part by grants AI088335 from the National Institute of Allergy and Infectious Disease, National Institutes of Health and TW008138-A1 a Fogarty International Research Chlormezanone Collaboration Award from the National Institutes of

Health. Electronic supplementary material Additional file 1: Table S1: List of GenBank accession numbers of dengue virus samples investigated in the study. The country and year of collection of samples are also provided. (XLSX 14 KB) Additional file 2: Table S2: Relative rate of nucleotide substitutions (based on HKY85 model) within serotypes of dengue virus. (DOCX 14 KB) Additional file 3: Table S3: Distribution of synonymous (syn) and non-synonymous (non-syn) sites among different genes of dengue virus. The numbers in parenthesis are counts of substitutions that are fixed within serotypes. The p value shows statistical significance of association between synonymous or nonsynonymous sites with or without tendency of fixation in each gene.