Codon Usage Bias And Evolutionary Analyses Of Zika And Crimean-congo Hemorrhagic Fever Virus Genomes And Its Adaptation To Hosts

Like all members of Flaviviridae,Zika virus harbors single stranded RNA genome that directly regulate central dogma.Zika virus(ZIKV)is a member of the family Flaviviridae and contains a single-stranded RNA genome with positive-polarity.Like Dengue,Zika virus is spread by Aedes aegypti mosquito used as a vector to infect human with a wide range of clinical signs,from asymptomatic to influenza-like syndrome.Despite significant progress in genomic analyses,how a viral relationship with two different hosts affect the overall fitness,constancy,and dodging of hosts immune system are elusive.Here we analyzed Zika virus codon-based evolution using eleven strains from different geographical locations.We performed various analysis by calculating several codon usage indices and applying multivariate statistical methods.Nucleotide composition and relative synonymous codon usage(RSCU)analysis revealed that ZIKV shows mutation bias and prefers A and U-ended codons to code amino acids.Effective number of codons analysis indicated that the overall codon usage is similar and slightly biased among all the strains.Codon usage patterns of ZIKV were also found to be influenced by its hosts.Similarity index analysis showed that the overall codon usage patterns of ZIKV have been strongly influenced by Aedes aegypti during evolution.Furthermore,various approaches strongly suggest that mutational bias is the main force shaping codon usage in this virus.However,natural selection and geographical realities cannot be ignored in marginal influence on codon usage.The viral genomes naturally favor Aedes aegypti over human host for tRNA pool in translation.These findings will assist researchers in understanding elements contributing to viral adaptation and evolutionary setup with hosts.Crimean-Congo hemorrhagic fever virus(CCHFV)is a negative-sense,single stranded RNA virus with a three-segmented genome that belongs to the genus Nairovirus within the family Bunyaviridae.CCHFV uses Hyalomma ticks as a vector to infect humans with a wide range of clinical signs,from asymptomatic to Zika-like syndrome.Despite significant progress in genomic analyses,the influences of viral relationships with different hosts on overall viral fitness,survival,and evading the host's immune systems remain unknown.To better understand the evolutionary characteristics of CCHFV,we performed a comprehensive analysis of the codon usage pattern in 179 CCHFV strains by calculating the relative synonymous codon usage(RSCU),effective number of codons(ENC),codon adaptation index(CAI),and other indicators.The results indicate that the codon usage bias of CCHFV is relatively low.Several lines of evidence support the hypothesis that a translation selection factor is shaping codon usage pattern in this virus.A correspondence analysis(CA)showed that other factors,such as base composition,aromaticity,and hydrophobicity may also be involved in shaping the codon usage pattern of CCHFV.Additionally,the results from a comparative analysis of RSCU between CCHFV and its hosts suggest that CCHFV tends to evolve codon usage patterns that are comparable to those of its hosts.Furthermore,the selection pressures from Homo sapiens,Bos taurus,and Ovis aries on the CCHFV RSCU patterns were dominant when compared with selection pressure from Hyalomma spp.vectors.Taken together,both natural selection and mutation pressure are important for shaping the codon usage pattern of CCHFV.We believe that such findings will assist researchers in understanding the evolution of CCHFV and its adaptation to its hosts.