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. 2015 Mar 30;112(15):4749–4754. doi: 10.1073/pnas.1502864112

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Freely available online through the PNAS open access option.

PMC Copyright notice

Fig. 1. — Codon pair bias in humans and mosquitoes. (A) Codon pair preferences are well-correlated (Spearman rho = 0.95) between humans and mice. Human codon pair preferences were calculated as described before (16); those for insects were calculated using genomic sequences of Aedes aegypti. (B) Codon pair preferences are poorly correlated (Spearman rho = 0.26) between humans and mosquitoes. Each circle represents one of the 3,721 possible codon pairs. (C) Codon pairs actually used by natural wild-type dengue virus, type 2 (16681) (red dots). The more times a particular codon pair is used by the virus, the bigger and more red the dot. (D) Codon pairs used by an in silico recoded dengue virus designed to have a good codon pair score in mosquitoes but a bad (negative) codon pair score in humans (blue dots). “hmin” signifies a human minimized virus. (E) The average human codon pair score of the in silico hmin virus (red dot) compared with WT (black dot) and the average codon pair scores of >14,000 human coding genes. (F) The same two viruses as in E (red and black dots) evaluated using mosquito codon pair scores and compared with all Aedes aegypti mosquito coding genes. The in silico hmin virus demonstrates that it is possible to design a synthetic dengue virus drastically deoptimized in humans but optimized in mosquitoes.