Effects of Arbovirus Multi-Host Life Cycles on Dinucleotide and Codon Usage Patterns

Abstract

Arthropod-borne viruses (arboviruses) of vertebrates including dengue, zika, chikungunya, Rift Valley fever, and blue tongue viruses cause extensive morbidity and mortality in humans, agricultural animals, and wildlife across the globe. As obligate intercellular pathogens, arboviruses must be well adapted to the cellular and molecular environment of both their arthropod (invertebrate) and vertebrate hosts, which are vastly different due to hundreds of millions of years of separate evolution. Here we discuss the comparative pressures on arbovirus RNA genomes as a result of a dual host life cycle, focusing on pressures that do not alter amino acids. We summarize what is currently known about arboviral genetic composition, such as dinucleotide and codon usage, and how cyclical infection of vertebrate and invertebrate hosts results in different genetic profiles compared with single-host viruses. To serve as a comparison, we compile what is known about arthropod tRNA, dinucleotide, and codon usages and compare this with vertebrates. Additionally, we discuss the potential roles of genetic robustness in arboviral evolution and how it may vary from other viruses. Overall, both arthropod and vertebrate hosts influence the resulting genetic composition of arboviruses, but a great deal remains to be investigated.

Keywords: arbovirus; arthropod-borne viruses; codon; dinucleotide; diversification; mosquito; purifying selection; robustness.

Figure 1

tRNA isoacceptor abundances in Aedes aegypti and Anopheles gambiae mosquitoes. (A) Relative abundance of isoacceptor tRNAs (RAIT) values for Ae. aegypti and An. gambiae mosquitoes. Underabundant tRNAs in both species that are likely due to avoidance of TpA dinucleotides or one-to-stop (OTS) codons are highlighted. RAIT values for (B) Ae. aegypti and (C) An. gambiae were plotted together with relative synonymous codon usage (RSCU) data. There is an imperfect correlation between the two relative abundances demonstrating the complexity of the tRNA-codon usage relationship. Data adapted from Behura and Severson (2011) [60].

Figure 2

Over and underabundant codons in Flaviviridae and hosts. (A) Codons with RSCU values over 1.38 (dotted line) are shown for host and Flaviviridae viruses. Those that are likely the result of compensation for CpG avoidance are highlighted, as are OTS codons. (B) Gly, Arg, Ser, and Leu OTS codon usage is shown across Flaviviridae viruses and hosts. OTS codons are selected against in most systems investigated, likely to avoid lethal non-sense mutations, but are relatively abundant in insect-infecting flaviviruses. Dotted lines represent 1.38 and 0.62. Data adapted from Lobo et al. (2009) [9].