{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:08:14Z","timestamp":1790370494749,"version":"4.1.0"},"reference-count":77,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T00:00:00Z","timestamp":1601251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israeli Science Foundation","doi-asserted-by":"crossref","award":["1333\/16"],"award-info":[{"award-number":["1333\/16"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,23]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>RNA viruses are responsible for some of the worst pandemics known to mankind, including outbreaks of Influenza, Ebola, and COVID-19. One major challenge in tackling RNA viruses is the fact they are extremely genetically diverse. Nevertheless, they share common features that include their dependence on host cells for replication, and high mutation rates. We set out to search for shared evolutionary characteristics that may aid in gaining a broader understanding of RNA virus evolution, and constructed a phylogeny-based data set spanning thousands of sequences from diverse single-stranded RNA viruses of animals. Strikingly, we found that the vast majority of these viruses have a skewed nucleotide composition, manifested as adenine rich (A-rich) coding sequences. In order to test whether A-richness is driven by selection or by biased mutation processes, we harnessed the effects of incomplete purifying selection at the tips of virus phylogenies. Our results revealed consistent mutational biases toward U rather than A in genomes of all viruses. In +ssRNA viruses, we found that this bias is compensated by selection against U and selection for A, which leads to A-rich genomes. In \u2212ssRNA viruses, the genomic mutational bias toward U on the negative strand manifests as A-rich coding sequences, on the positive strand. We investigated possible reasons for the advantage of A-rich sequences including weakened RNA secondary structures, codon usage bias, and selection for a particular amino acid composition, and conclude that host immune pressures may have led to similar biases in coding sequence composition across very divergent RNA viruses.<\/jats:p>","DOI":"10.1093\/molbev\/msaa247","type":"journal-article","created":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T03:30:28Z","timestamp":1601004628000},"page":"575-588","source":"Crossref","is-referenced-by-count":76,"title":["Biased Mutation and Selection in RNA Viruses"],"prefix":"10.1093","volume":"38","author":[{"given":"Talia","family":"Kustin","sequence":"first","affiliation":[{"name":"The Shmunis School of Biomedicine and Cancer Research, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2919-3542","authenticated-orcid":false,"given":"Adi","family":"Stern","sequence":"additional","affiliation":[{"name":"The Shmunis School of Biomedicine and Cancer Research, Tel Aviv University, Tel Aviv, Israel"},{"name":"Edmond J. Safra Center for Bioinformatics, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,9,28]]},"reference":[{"issue":"W1","key":"2021012317494262400_msaa247-B1","doi-asserted-by":"crossref","first-page":"W580","DOI":"10.1093\/nar\/gks498","article-title":"FastML: a web server for probabilistic reconstruction of ancestral sequences","volume":"40","author":"Ashkenazy","year":"2012","journal-title":"Nucleic Acids Res"},{"issue":"7","key":"2021012317494262400_msaa247-B2","doi-asserted-by":"crossref","first-page":"4527","DOI":"10.1093\/nar\/gku075","article-title":"The influence of CpG and UpA dinucleotide frequencies on RNA virus replication and characterization of the innate cellular pathways underlying virus attenuation and enhanced replication","volume":"42","author":"Atkinson","year":"2014","journal-title":"Nucleic Acids 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