Bicluster pattern of codon context usages between flavivirus and vector mosquito Aedes aegypti: relevance to infection and transcriptional response of mosquito genes

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 inusages 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 contexts bias in evolution of vector-virus interactions at the molecular level.

Does adaptation to vertebrate codon usage relate to flavivirus emergence potential?

“…Therefore, versatility in gene expression and protein synthesis is at premium, and certain changes in the viral RNA genome could affect the fitness of the virus in a specific host. Indeed, viral fitness changes relate to dinucleotide frequencies, codon preferences, and codon pair biases [ 5 , 14 , 15 , 53 , 54 ].…”

“…Ecology, different virus-host relationships and biogeographical migrations of flavivirus species may explain observed genetic differences among subgroups [ 13 , 15 , 16 , 55 , 56 ]. Phylogenetic studies have acknowledged three groups that reflect the evolutionary and ecological dynamics: tick-borne, mosquito-borne ( Aedes and Culex species), and no known-vector flaviviruses [ 57 – 63 ].…”

Full-Genome Characterization and Genetic Evolution of West African Isolates of Bagaza Virus

“…Flaviviruses can infect and replicate in hosts of different phyla. Therefore, their versatility in gene expression and protein synthesis and changes in the viral RNA genome could affect the fitness of the virus in a specific host relating to dinucleotide frequencies, codon preferences, and codon pair biases [ 97 , 98 , 99 ]. Nevertheless, ecology, different virus-host relationships, biogeographical migrations of flavivirus species and genetic differences may explain observed differences in flaviviral codon usage preference to human housekeeping genes [ 98 , 100 , 101 ].…”

Genome Investigations of Vector Competence in Aedes aegypti to Inform Novel Arbovirus Disease Control Approaches

“…We also observed that codon context (the propensity of adjacent codons to consistently pair with themselves or another codon) among Asian and American DENV isolates showed a bias toward (A)(A/T)(A)-(A)(A/T)(A) coding sequences and general avoidance of (C/G)(C/A)(C/G)-(C/G)(C/A)(C/G) coding sequences across all four serotypes [119]. In addition to DENV, we also compared [121] the codon context bias of other flaviviruses, including West Nile virus (WNV) and yellow fever virus (YFV), and determined that codon context bias varies in a bicluster manner with A. aegypti genes that have been shown to be differentially expressed following infection by these viruses [92]. This result suggests that codon context sequences of A. aegypti and the flaviviruses may play an important role in determining successful infection by these viruses.…”