Abstract
The mosquito Aedes aegypti is the primary vector of dengue virus (DENV) infection in most of the subtropical and tropical countries. Besides DENV, yellow fever virus (YFV) is also transmitted by A. aegypti. Susceptibility of A. aegypti to West Nile virus (WNV) has also been confirmed. Although studies have indicated correlation of codon bias between flaviviridae and their animal/insect hosts, it is not clear if codon sequences have any relation to susceptibility of A. aegypti to DENV, YFV and WNV. In the current study, usages of codon context sequences (codon pairs for neighboring amino acids) of the vector (A. aegypti) genome as well as the flaviviral genomes are investigated. We used bioinformatics methods to quantify codon context bias in a genome-wide manner of A. aegypti as well as DENV, WNV and YFV sequences. Mutual information statistics was applied to perform bicluster analysis of codon context bias between vector and flaviviral sequences. Functional relevance of the bicluster pattern was inferred from published microarray data. Our study shows that codon context bias of DENV, WNV and YFV sequences varies in a bicluster manner with that of specific sets of genes of A. aegypti. Many of these mosquito genes are known to be differentially expressed in response to flaviviral infection suggesting that codon context sequences of A. aegypti and the flaviviruses may play a role in the susceptible interaction between flaviviruses and this mosquito. The bias in usages of codon context sequences likely has a functional association with susceptibility of A. aegypti to flaviviral infection. The results from this study will allow us to conduct hypothesis-driven tests to examine the role of codon context bias in evolution of vector–virus interactions at the molecular level.
Similar content being viewed by others
References
Akashi H (2001) Gene expression and molecular evolution. Curr Opin Genet Dev 11:660–666
Anderson MJ (2001) A new method for non-parametric multivariate analysis of variance. Austral Ecol 26:32–46
Anderson MJ, Willis TJ (2003) Canonical analysis of principal coordinates: a useful method of constrained ordination for ecology. Ecology 84:511–525
Barrett AD, Higgs S (2007) Yellow fever: a disease that has yet to be conquered. Annu Rev Entomol 52:209–229
Behura SK, Severson DW (2011) Coadaptation of isoacceptor tRNA genes and codon usage bias for translation efficiency in Aedes aegypti and Anopheles gambiae. Insect Mol Biol 20:177–187
Behura SK, Severson DW (2012a) Intrinsic features of Aedes aegypti genes affect transcriptional responsiveness of mosquito genes to dengue virus infection. Infect Genet Evol 12:1413–1418
Behura SK, Severson DW (2012b) Comparative analysis of codon usage bias and codon context patterns between Dipteran and Hymenopteran sequenced genomes. PLoS One 7:e43111
Behura SK, Severson DW (2013a) Codon usage bias: causative factors, quantification methods and genome-wide patterns: with emphasis on insect genomes. Biol Rev 88:49–61
Behura SK, Severson DW (2013b) Nucleotide substitutions in dengue virus serotypes from Asian and American countries: insights into intracodon recombination and purifying selection. BMC Microbiol 13:37
Behura SK, Gomez-Machorro C, Harker BW, deBruyn B, Lovin DD, Hemme RR, Mori A, Romero-Severson J, Severson DW (2011) Global cross-talk of genes of the mosquito Aedes aegypti in response to dengue virus infection. PLoS Negl Trop Dis 5:e1385
Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, Drake JM, Brownstein JS, Hoen AG, Sankoh O, Myers MF, George DB, Jaenisch T, Wint GR, Simmons CP, Scott TW, Farrar JJ, Hay SI (2013) The global distribution and burden of dengue. Nature 496:504–507
Bossi L, Ruth JR (1980) The influence of codon context on genetic code translation. Nature 286:123–127
Buckingham RH (1990) Codon context. Experientia 46:1126–1133
Buckingham RH (1994) Codon context and protein synthesis: enhancements of the genetic code. Biochimie 76:351–354
Camiolo S, Farina L, Porceddu A (2012) The relation of codon bias to tissue-specific gene expression in Arabidopsis thaliana. Genetics 192:641–649
Center for Disease Control and Prevention (2013) West Nile virus in the United States: guidelines for surveillance, prevention, and control. http://www.cdc.gov/ncidod/dvbid/westnile/mosquitospecies.htm. Accessed 21 Dec 2013
Chauhan C, Behura SK, Debruyn B, Lovin DD, Harker BW, Gomez-Machorro C, Mori A, Romero-Severson J, Severson DW (2012) Comparative expression profiles of midgut genes in dengue virus refractory and susceptible Aedes aegypti across critical period for virus infection. PLoS One 7:e47350
Coleman JR, Papamichail D, Skiena S, Futcher B, Wimmer E, Mueller S (2008) Virus attenuation by genome-scale changes in codon pair bias. Science 320:1784–1787
Colpitts TM, Cox J, Vanlandingham DL, Feitosa FM, Cheng G, Kurscheid S, Wang P, Krishnan MN, Higgs S, Fikrig E (2011) Alterations in the Aedes aegypti transcriptome during infection with West Nile, dengue and yellow fever viruses. PLoS Pathog 7:e1002189
Cook S, Bennett SN, Holmes EC, De Chesse R, Moureau G, de Lamballerie X (2006) Isolation of a new strain of the flavivirus cell fusing agent virus in a natural mosquito population from Puerto Rico. J Gen Virol 87:735–748
de Hoon MJ, Imoto S, Nolan J, Miyano S (2004) Open source clustering software. Bioinformatics 20:1453–1454
Gardner CL, Ryman KD (2010) Yellow fever: a reemerging threat. Clin Lab Med 30:237–260
Girard YA, Mayhew GF, Fuchs JF, Li H, Schneider BS, McGee CE, Rocheleau TA, Helmy H, Christensen BM, Higgs S, Bartholomay LC (2010) Transcriptome changes in Culex quinquefasciatus (Diptera: Culicidae) salivary glands during West Nile virus. J Med Entomol 47:421–435
Gould EA, Solomon T (2008) Pathogenic flaviviruses. Lancet 371:500–509
Gupta N, Aggarwal S (2008) MIBiClus: mutual Information based biclustering algorithm. Int J Comput Sci 3:2
Guzman MG, Halstead SB, Artsob H, Buchy P, Farrar J, Gubler DJ, Hunsperger E, Kroeger A, Margolis HS, Martínez E, Nathan MB, Pelegrino JL, Simmons C, Yoksan S, Peeling RW (2010) Dengue: a continuing global threat. Nat Rev Microbiol 8:S7–S16
Hayes EB, Sejvar JJ, Zaki SR, Lanciotti RS, Bode AV, Campbell GL (2005) Virology, pathology, and clinical manifestations of West Nile virus disease. Emerg Infect Dis 11:1174–1179
Heinz FX, Stiasny K (2012) Flaviviruses and flavivirus vaccines. Vaccine 30:4301–4306
Hsieh SC, Liu IJ, King CC, Chang GJ, Wang WK (2008) A strong endoplasmic reticulum retention signal in the stem-anchor region of envelope glycoprotein of dengue virus type 2 affects the production of virus-like particles. Virology 374:338–350
Irwin B, Heck JD, Hatfield GW (1995) Codon pair utilization biases influence translational elongation step times. J Biol Chem 270:22801–22806
Lobo FP, Mota BE, Pena SD, Azevedo V, Macedo AM, Tauch A, Machado CR, Franco GR (2009) Virus-host coevolution: common patterns of nucleotide motif usage in Flaviviridae and their hosts. PLoS One 4:e6282
Mackenzie JS, Gubler DJ, Petersen LR (2004) Emerging flaviviruses: the spread and resurgence of Japanese encephalitis, West Nile and dengue viruses. Nat Med 10:S98–S109
Mantel N (1967) The detection of disease clustering and a generalized regression approach. Cancer Res 27:209–220
Moura G, Pinheiro M, Silva R, Miranda I, Afreixo V, Dias G, Freitas A, Oliveira JL, Santos MA (2005) Comparative context analysis of codon pairs on an ORFeome scale. Genome Biol 6:R28
Moura G, Pinheiro M, Arrais J, Gomes AC, Carreto L, Freitas A, Oliveira JL, Santos MA (2007) Large scale comparative codon-pair context analysis unveils general rules that fine-tune evolution of mRNA primary structure. PLoS One 2:e847
Mueller S, Papamichail D, Coleman JR, Skiena S, Wimmer E (2006) Reduction of the rate of poliovirus protein synthesis through large-scale codon deoptimization causes attenuation of viral virulence by lowering specific infectivity. J Virol 80:9687–9696
Najafabadi HS, Salavati R (2008) Sequence-based prediction of protein–protein interactions by means of codon usage. Genome Biol 9:R87
Najafabadi HS, Goodarzi H, Salavati R (2009) Universal function-specificity of codon usage. Nucleic Acids Res 37:7014–7023
Novoa EM, Ribas de Pouplana L (2012) Speeding with control: codon usage, tRNAs, and ribosomes. Trends Genet 28:574–581
Pugachev KV, Guirakhoo F, Monath TP (2005) New developments in flavivirus vaccines with special attention to yellow fever. Curr Opin Infect Dis 18:387–394
Ramirez JL, Dimopoulos G (2010) The Toll immune signaling pathway control conserved anti-dengue defenses across diverse Ae. aegypti strains and against multiple dengue virus serotypes. Dev Comp Immunol 34:625–629
Rocha EP (2004) Codon usage bias from tRNA’s point of view: redundancy, specialization, and efficient decoding for translation optimization. Genome Res 14:2279–2286
Rodriguez O, Singh BK, Severson DW, Behura SK (2012) Translational selection of genes coding for perfectly conserved proteins among three mosquito vectors. Infect Genet Evol 12:1535–1542
Rossi SL, Ross TM, Evans JD (2010) West Nile virus. Clin Lab Med 30:47–65
Sim S, Dimopoulos G (2010) Dengue virus inhibits immune responses in Aedes aegypti cells. PLoS One 5:e10678
Solomon T, Mallewa M (2001) Dengue and other emerging flaviviruses. J Infect 42:104–115
Souza-Neto JA, Sim S, Dimopoulos G (2009) An evolutionary conserved function of the JAK-STAT pathway in anti-dengue defense. Proc Natl Acad Sci USA 106:17841–17846
Suthar MS, Diamond MS, Gale M Jr (2013) West Nile virus infection and immunity. Nat Rev Microbiol 11:115–128
Turell MJ, O’Guinn ML, Dohm DJ, Jones JW (2001) Vector competence of North American mosquitoes (Diptera: Culicidae) for West Nile virus. J Med Entomol 8:130–134
Vanlandingham DL, McGee CE, Klinger KA, Vessey N, Fredregillo C, Higgs S (2007) Relative susceptibilties of South Texas mosquitoes to infection with West Nile virus. Am J Trop Med Hyg 77:925–928
Xi Z, Ramirez JL, Dimopoulos G (2008) The Aedes aegypti toll pathway controls dengue virus infection. PLoS Pathog 4:e1000098
Acknowledgments
The authors are thankful to Casey Hill for critically reading the manuscript. This study was supported in part from grant RO3-TW008138, Fogarty International Research Collaboration Award (FIRCA), National Institutes of Health (NIH), USA.
Author information
Authors and Affiliations
Corresponding author
Additional information
Communicated by S. Hohmann.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Behura, S.K., Severson, D.W. Bicluster pattern of codon context usages between flavivirus and vector mosquito Aedes aegypti: relevance to infection and transcriptional response of mosquito genes. Mol Genet Genomics 289, 885–894 (2014). https://doi.org/10.1007/s00438-014-0857-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00438-014-0857-x