Sequence analysis of SARS-CoV-2 genome reveals features important for vaccine design

Jacob Kames; David Dillon Holcomb; Ofer Kimchi; Michael DiCuccio; Nobuko Hamasaki-Katagiri; Tony Wang; Anton A Komar; Aikaterini Alexaki; Chava Kimchi-Sarfaty

Codon usage is biased across all domains of life, i.e., synonymous codons occur at different frequencies in different organisms [4, 5] . It is thought that preferred codons correspond to more abundant tRNAs, and therefore, are translated more efficiently [6] . Similarly, there is bias in codon pair usage, with certain codon pairs occurring at a much different frequency than would be expected based on the codon usage [5] . Codon pair usage also appears to affect translation efficiency [6] , although the mechanism is not entirely clear, and it has been argued that dinucleotide usage may be the driving force in determining viral sequence fitness, while codon pair bias may be a secondary effect of altered dinucleotide frequency [7] . Considering that viruses are obligate intracellular parasites and rely on the host-cell machinery for proper expression of their genes, it is worth noting that their codon usage often does not closely resemble the codon usage of their hosts [8, 9] , a phenomenon that is not well understood. In this regard, a thorough characterization of codon, codon pair and dinucleotide usage of SARS-CoV-2 can provide useful information regarding expression potential of the viral genes and the fitness of the virus in its human or other hosts. Furthermore, it has been shown that viral attenuation can be achieved through extensive changes in codon pair usage of viral genes [2] . Since the mechanism of viral attenuation through codon pair deoptimization is not entirely clear, this in-depth analysis is necessary to guide the development of new vaccines.