Evidence for selection on SARS-CoV-2 RNA translation revealed by the evolutionary dynamics of mutations in UTRs and CDSs

Abstract

RNA translation is the rate-limiting step when cells synthesize proteins. Elevating translation efficiency (TE) is intuitively beneficial. Particularly, when viruses invade host cells, how to compete with endogenous RNAs for efficient translation is a major issue to be resolved. We collected millions of worldwide SARS-CoV-2 sequences during the past year and traced the dynamics of allele frequency of every mutation. We defined adaptive and deleterious mutations according to the rise and fall of their frequencies along time. For 5ʹUTR and synonymous mutations in SARS-CoV-2, the selection on TE is evident near start codons. Adaptive mutations generally decrease GC content while deleterious mutations increase GC content. This trend fades away with increasing distance to start codons. Mutations decreasing GC content near start codons would unravel the complex RNA structure and facilitate translation initiation, which are beneficial to SARS-CoV-2, and vice versa. During this evolutionary arms race between human and virus, SARS-CoV-2 tries to improve its cis elements to compete with host RNAs for rapid translation.

uORF-Mediated Translational Regulation of ATF4 Serves as an Evolutionarily Conserved Mechanism Contributing to Non-Small-Cell Lung Cancer (NSCLC) and Stress Response

“…We obtained the population SNP data from multiple species. These SNP data include the human 1000 genome (Kuehn, 2008 ), Drosophila genetic reference panel (Mackay et al, 2012 ), 1000 genome project of Arabidopsis thaliana (Alonso-Blanco et al, 2016 ; Chu and Wei, 2021a ; Wei, 2020 ), and the SNPs called from millions of global SARS-CoV-2 sequences available in GISAID or relevant literatures (Cai et al, 2022 ; Li et al, 2020b ; Liu et al, 2022 ; Martignano et al, 2022 ; Shu and McCauley, 2017 ; Wei, 2022 ; Zhao et al, 2022 ; Zhu et al, 2022 ; Zong et al, 2022 ). We utilized these SNP data to test whether the mutations that abolish uORFs are most deleterious.…”

“…The SNPs in the population of Arabidopsis thaliana were retrieved from previous literatures (Alonso-Blanco et al, 2016 ; Chu and Wei, 2021a ; Wei, 2020 ). The sequences and SNPs of the world-wide SARS-CoV-2 population were downloaded from GISAID (Shu and McCauley, 2017 ) as previously literatures instructed (Liu et al, 2022 ; Zhu et al, 2022 ).…”

“…The SNP (single-nucleotide polymorphism) files of target species came from the following resources: the human 1000 genome project from (Kuehn, 2008 ) ( ftp://ftp.1000genomes.ebi.ac.uk/ ); the Drosophila genetic reference panel from (Mackay et al, 2012 ) ( http://dgrp2.gnets.ncsu.edu/ ); the 1000 genome project of Arabidopsis thaliana from (Alonso-Blanco et al, 2016 ; Chu and Wei, 2021a ; Wei, 2020 ); and the millions of world-wide SARS-CoV-2 sequences from (Liu et al, 2022 ; Shu and McCauley, 2017 ; Zhu et al, 2022 ).…”

Nothing in SARS-CoV-2 Makes Sense Except in the Light of Rna modification?

“…In theory, each RNA molecule should be regarded as ‘a virus individual’ and the unit of LD should be each ‘single sequencing read’. Unfortunately, in most SARS-CoV-2 literature dealing with ‘strains’ [ 18 , 19 ], one sequencing library from one host is regarded as ‘one strain’ to perform LD [ 17 ] regardless of the intra-host polymorphisms caused by deamination. Moreover, misdefinition of ‘a virus individual’ also affects the definition of population size N e .…”

Prediction of the effects of the top 10 synonymous mutations from 26645 SARS-CoV-2 genomes

“…Numerous studies have been carried out to understand the molecular mechanisms of these nonsynonymous mutations on the functions of different SARS-CoV-2 proteins 8 . However, there are only a few studies on the synonymous mutations of SARS-CoV-2 genome 9,10 .…”