On the Verge of Life: Distribution of Nucleotide Sequences in Viral RNAs.

The aim of the study is to analyze viruses using parameters obtained from distributions of nucleotide sequences in the viral RNA. Seeking for the input data homogeneity, we analyze single-stranded RNA viruses only. Two approaches are used to obtain the nucleotide sequences; In the first one, chunks of equal length (four nucleotides) are considered. In the second approach, the whole RNA genome is divided into parts by adenine or the most frequent nucleotide as a "space". Rank-frequency distributions are studied in both cases. The defined nucleotide sequences are signs comparable to a certain extent to syllables or words as seen from the nature of their rank-frequency distributions. Within the first approach, the Pólya and the negative hypergeometric distribution yield the best fit. For the distributions obtained within the second approach, we have calculated a set of parameters, including entropy, mean sequence length, and its dispersion. The calculated parameters became the basis for the classification of viruses. We observed that proximity of viruses on planes spanned on various pairs of parameters corresponds to related species. In certain cases, such a proximity is observed for unrelated species as well calling thus for the expansion of the set of parameters used in the classification. We also observed that the fifth most frequent nucleotide sequences obtained within the second approach are of different nature in case of human coronaviruses (different nucleotides for MERS, SARS-CoV, and SARS-CoV-2 versus identical nucleotides for four other coronaviruses). We expect that our findings will be useful as a supplementary tool in the classification of diseases caused by RNA viruses with respect to severity and contagiousness.