The numbers Cilengitide chemical structure of such codons (Syn_multiple and Nonsyn_multiple) are shown along with codons where only one site has a substitution. Fixation of synonymous versus non-synonymous substitutions in DENV genes Many substitutions show fixation tendency in DENV. This was 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). The number of such sites and the total number of substitutions in individual genes are listed in Additional file 3. It shows that the fixed sites are differentially
distributed among the genes. Based on 2×2 contingency tests (Pearson Chi Square), it was found that synonymous or non-synonymous sites which show fixation or non-fixation tendency among samples are significantly biased in specific genes of DENV. Genes encoding membrane glycoprotein precursor M, envelope protein E, and nonstructural proteins NS2A and NS5 show significant bias in the fixed and non-fixed substitutions in serotype 1. In serotype 2, only two genes (anchored capsid
protein C and nonstructural protein NS4B) show such a pattern, whereas only one gene (nonstructural protein NS3) reflects this pattern in serotype 3. In the serotype 4 isolates, no gene shows such substitution sites. In serotype 4 isolates, only learn more 2-4% of the substitution sites are fixed between Central and Southern American DENV isolates compared to 30-40% of such sites between Asian and American serotype 1, 2 and 3 DENV isolates. It was also
selleck chemicals observed that geographical populations within serotypes show extensive codon usage bias. Based on the relative synonymous codon usage (RSCU) index of dengue samples of Asia and America (or South and Central selleck compound America), it was found that codon preferences or non-preferences were significant between geographical origins (Table 3). In the serotype 3 isolates, the association of codon preferences or non-preferences between American and Asian countries was not significant, although rare codon fixation was higher in frequency than that of frequent codons. Table 3 Codon usage bias in dengue virus DENV-1 RSCU > 1 in Asian DENV RSCU < 1 in Asian DENV p value RSCU > 1 in American DENV 91 160 0.02 RSCU <1 in American DENV 193 112 DENV-2 RSCU > 1 in Asian DENV RSCU < 1 in Asian DENV RSCU > 1 in American DENV 35 121 0.000004 RSCU <1 in American DENV 155 79 DENV-3 RSCU > 1 in Asian DENV RSCU < 1 in Asian DENV RSCU > 1 in American DENV 80 132 0.08 RSCU <1 in American DENV 138 116 DENV-4 RSCU > 1 in Central American DENV RSCU <1 in South American DENV RSCU > 1 in Central American DENV 5 13 0.