Abstract
We first conducted time-series analysis of mono- and dinucleotide composition for over 10,000 SARS-CoV-2 genomes, as well as over 1500 Zaire ebolavirus genomes, and found clear time-series changes in the compositions on a monthly basis, which should reflect viral adaptations for efficient growth in human cells. We next developed a sequence alignment free method that extensively searches for advantageous mutations and rank them in an increase level for their intrapopulation frequency. Time-series analysis of occurrences of oligonucleotides of diverse lengths for SARS-CoV-2 genomes revealed seven distinctive mutations that rapidly expanded their intrapopulation frequency and are thought to be candidates of advantageous mutations for the efficient growth in human cells.
Highlights
Time-series changes in mononucleotide composition To investigate whether time-series changes, which were previously found for Zaire ebolavirus, MERS coronavirus and influenza virus (Wada et al, 2016), occur in SARS-CoV-2 isolated from humans, we plotted the mononucleotide composition (%) of each strain of SARS-CoV-2 in an order corresponding the isolation date, after the removal of the polyA-tail in advance (Fig. 1a)
We first noticed the presence of the data that appear to be outliers and found that these were often derived from the sequences where the number of Ns is greater than 1000; this should be an unavoidable situation in the case of urgent sequencing, such as SARS-CoV-2
When shortening the oligonucleotide length to 4-mer, there appeared two cases with over 200% increase, and this was because the highest UUUU has the mutation in both Seq1 and 2 and the second highest UUAC has the mutation in both Seq2 and 3 (Fig. 4)
Summary
Efficient growth after the invasion will likely require changes in the virus genome To study this viral adaptation, we previously analyzed time-series changes in mono- and oligonucleotide compositions of three zoonotic RNA viruses (Zaire ebolavirus, MERS coronavirus and influenza virus) and identified time-series directional changes that were detectable even on a monthly basis (Iwasaki et al, 2011, 2013; Wada et al, 2016). An analysis of 25,000 influenza virus genomes showed that the directional changes were very similar between H1N1 (starting in 1918), H3N2 (starting in 1968) and H1N1/2009 (starting in 2009) (Wada et al, 2016) These reproducible changes of the three independent invasions should reflect viral adaptive processes for efficient growth in human cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
