Compositional Variability and Mutation Spectra of Monophyletic SARS-CoV-2 Clades.
Xufei Teng, Qianpeng Li, Zhao Li, Yuansheng Zhang, Guangyi Niu, Jingfa Xiao, Jun Yu, Zhang Zhang, Shuhui Song
Author Information
Xufei Teng: China National Center for Bioinformation, Beijing 100101, China; National Genomics Data Center & CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Qianpeng Li: China National Center for Bioinformation, Beijing 100101, China; National Genomics Data Center & CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Zhao Li: China National Center for Bioinformation, Beijing 100101, China; National Genomics Data Center & CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Yuansheng Zhang: China National Center for Bioinformation, Beijing 100101, China; National Genomics Data Center & CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Guangyi Niu: China National Center for Bioinformation, Beijing 100101, China; National Genomics Data Center & CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Jingfa Xiao: China National Center for Bioinformation, Beijing 100101, China; National Genomics Data Center & CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Jun Yu: China National Center for Bioinformation, Beijing 100101, China; National Genomics Data Center & CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: junyu@big.ac.cn.
Zhang Zhang: China National Center for Bioinformation, Beijing 100101, China; National Genomics Data Center & CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: zhangzhang@big.ac.cn.
Shuhui Song: China National Center for Bioinformation, Beijing 100101, China; National Genomics Data Center & CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: songshh@big.ac.cn.
COVID-19 and its causative pathogen SARS-CoV-2 have rushed the world into a staggering pandemic in a few months, and a global fight against both has been intensifying. Here, we describe an analysis procedure where genome composition and its variables are related, through the genetic code to molecular mechanisms, based on understanding of RNA replication and its feedback loop from mutation to viral proteome sequence fraternity including effective sites on the replicase-transcriptase complex. Our analysis starts with primary sequence information, identity-based phylogeny based on 22,051 SARS-CoV-2 sequences, and evaluation of sequence variation patterns as mutation spectra and its 12 permutations among organized clades. All are tailored to two key mechanisms: strand-biased and function-associated mutations. Our findings are listed as follows: 1) The most dominant mutation is C-to-U permutation, whose abundant second-codon-position counts alter amino acid composition toward higher molecular weight and lower hydrophobicity, albeit assumed most slightly deleterious. 2) The second abundance group includes three negative-strand mutations (U-to-C, A-to-G, and G-to-A) and a positive-strand mutation (G-to-U) due to DNA repair mechanisms after cellular abasic events. 3) A clade-associated biased mutation trend is found attributable to elevated level of negative-sense strand synthesis. 4) Within-clade permutation variation is very informative for associating non-synonymous mutations and viral proteome changes. These findings demand a platform where emerging mutations are mapped onto mostly subtle but fast-adjusting viral proteomes and transcriptomes, to provide biological and clinical information after logical convergence for effective pharmaceutical and diagnostic applications. Such actions are in desperate need, especially in the middle of the War against COVID-19.
