Abstract
BackgroundWhen a virus that has grown in a nonhuman host starts an epidemic in the human population, human cells may not provide growth conditions ideal for the virus. Therefore, the invasion of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which is usually prevalent in the bat population, into the human population is thought to have necessitated changes in the viral genome for efficient growth in the new environment. In the present study, to understand host-dependent changes in coronavirus genomes, we focused on the mono- and oligonucleotide compositions of SARS-CoV-2 genomes and investigated how these compositions changed time-dependently in the human cellular environment. We also compared the oligonucleotide compositions of SARS-CoV-2 and other coronaviruses prevalent in humans or bats to investigate the causes of changes in the host environment.ResultsTime-series analyses of changes in the nucleotide compositions of SARS-CoV-2 genomes revealed a group of mono- and oligonucleotides whose compositions changed in a common direction for all clades, even though viruses belonging to different clades should evolve independently. Interestingly, the compositions of these oligonucleotides changed towards those of coronaviruses that have been prevalent in humans for a long period and away from those of bat coronaviruses.ConclusionsClade-independent, time-dependent changes are thought to have biological significance and should relate to viral adaptation to a new host environment, providing important clues for understanding viral host adaptation mechanisms.
Highlights
When a virus that has grown in a nonhuman host starts an epidemic in the human population, human cells may not provide growth conditions ideal for the virus
Our previous work on influenza A-type virus genomes found that the oligonucleotide compositions of the viral genomes differed between hosts, even for viruses within the same subtype (e.g., H1N1 and H3N2 of type A) [11, 12, 14]; we examined changes in the oligonucleotide compositions of influenza H1N1/09, which have been epidemic in humans beginning in 2009, and found that their compositions changed to approach those of the seasonal flu strains H1N1 and H3N2 [11]
The prevalence C → U change in SARS-CoV-2 upon transfer of its host environment from bats to humans suggests that these changes may be due to human-specific APOBEC genes
Summary
When a virus that has grown in a nonhuman host starts an epidemic in the human population, human cells may not provide growth conditions ideal for the virus. Severe acute respiratory syndrome coronavirus-2 (SARSCoV-2), an RNA virus belonging to the betacoronavirus genus, began to spread in the human population in 2019 This viral strain is believed to have been originally prevalent in bats and transferred to the human population. Due to the great threat of COVID-19 and remarkable development of sequencing technology, a massive number of SARS-CoV-2 genome sequences are available in databases, even though the epidemic has lasted for approximately 10 months. These sequence data have provided a wide range of insights into SARS-CoV-2 [5, 6]. When dealing with a massive number of genome sequences, methods based on sequence alignment become problematic because they require a large amount of computational resources
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