Rapid protein sequence evolution via compensatory frameshift is widespread in RNA virus genomes

Park, Dongbin; Hahn, Yoonsoo

doi:10.1186/s12859-021-04182-9

Cited by 9 publications

(21 citation statements)

References 58 publications

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“…Few studies have been reported regarding FSMs in the evolution of viruses, including the viruses in the 13 families (Hughes, et al 2010; Taubenberger and Kash 2010; Breitbart, et al 2017; Simmonds, et al 2017; Zell, et al 2017; Chen, et al 2018; Laenen, et al 2019; Radoshitzky, et al 2019; Rima, et al 2019; Garrison, et al 2020; Hughes, et al 2020; Sun, et al 2022; Zmasek, et al 2022). This could be partially because researchers usually focused on virus evolution on small scales (e.g., intra-species evolution or microevolution of influenza virus or SARS-CoV-2), and FSMs are relatively rare in virus evolution on small scale, as revealed by this report and a previous report (Park and Hahn 2021). Consequently, we had the opportunity in this study to reveal frequencies and multiple features of FSMs in virus evolution on various scales for the first time.…”

Section: Discussionmentioning

confidence: 73%

“…The copyright holder for this preprint this version posted July 21, 2022. ; https://doi.org/10.1101/2022.07.20.500745 doi: bioRxiv preprint Previous reports classified FSMs into 2-indel compensatory FSMs and non-compensatory FSMs, and one report suggested that their frequencies are similar (Park and Hahn 2021;Rogers, et al 2021). Here we identified that, from a broader view, there were 3-, 4-, and 5-indel compensatory FSMs in virus evolution, besides 1-indel non-compensatory FSMs and 2-indel compensatory FSMs (fig.…”

Section: Discussionmentioning

confidence: 99%

“…Because FSMs occurred frequently in the genomes of some species in some families, phylogenetic relationships of some viruses calculated with amino acid sequences could be somehow unreliable because one 2-indel compensatory FSM could be counted as multiple nucleotide substitutions through alignment of the relevant amino acid sequences (Park and Hahn 2021).…”

Section: Discussionmentioning

confidence: 99%

“…Few studies on FSMs in the evolution of viruses have been reported. A recent milestone study parsed 1,233,275 viral sequences of 10,115 genes of many RNA viruses, and found that FSMs occurred in the evolution of 385 genes on small scales (i.e., sequence identities >97%) (Park and Hahn 2021). For instance, 2 of 5,606 the hemagglutinin gene sequences (sequence identities >97%) of H1 subtype influenza virus carried FSMs, and 6 of 685 the hemagglutinin neuraminidase (HN) gene sequences of paramyxoviruses (sequence identities >97%) carried FSMs (Park and Hahn 2021).…”

Section: Introductionmentioning

confidence: 99%

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Frameshift Mutations in the Microevolution and Macroevolution of Viruses

Shao

Sun

et al. 2022

Preprint

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Some nucleotide insertions or deletions (indels) in protein-coding open reading frames lead to frameshift mutations (FSMs) which can change amino acid sequences drastically. FSMs are widely distributed in the genomes of many organisms. However, few studies have been reported regarding frequencies of FSMs in microevolution or macroevolution. Many viruses evolve much more rapidly than cellular organisms, and they are hence suitable to investigate frequencies of FSMs in microevolution or macroevolution. In this report, we identified 667 FSMs in gene sequences of 13 virus families and each FSM changed approximately 11 amino acid residues on average. Of the FSMs, 89.21% were 2-indel compensatory FSMs, and the remaining were 1-, 3-, 4-, 5-indel FSMs. We found that FSMs usually occurred more frequently in the viruses of the same family with smaller sequence identities, and FSMs occurred in the sequences of with identities of 60.0−69.9% more frequently than in the sequences with identities of 90.0−99.9% or 80.0−89.9% by approximately 34.9 or 13.1 times on average. We also found FSMs occurred at different frequencies among genes in the same virus genome, among species in the same virus family, or among virus families (e.g., more frequently in Coronaviridae than in Orthomyxoviridae). These results suggest that FSMs are more frequent in the inter-species or macroevolution than in the intra-species or microevolution of viruses. They provide novel evidence for the hopeful monster hypothesis in evolutionary biology. They inspire researchers to investigate the roles, frequencies, features, and functions of FSMs in other viruses and cellular organisms.

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Frameshift Mutations in the Microevolution and Macroevolution of Viruses

Shao

Sun

et al. 2022

Preprint

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“…It has been described in various viral genomes that frameshifting due to nucleotide insertions or deletions (indels), which may cause the premature termination of protein synthesis, can be restored to produce functional proteins by a secondary indel near the primary indel site. This phenomenon is known as "compensatory frameshift" [32], and may explain the low amino acid identity in LIS I and II. These LIS regions could be the result of successive indel followed by compensatory frameshift events.…”

Section: Discussionmentioning

confidence: 99%

New Insights into the Genome Organization of Yeast Double-Stranded RNA LBC Viruses

2022

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The yeasts Torulaspora delbrueckii (Td) and Saccharomyces cerevisiae (Sc) may show a killer phenotype that is encoded in dsRNA M viruses (V-M), which require the helper activity of another dsRNA virus (V-LA or V-LBC) for replication. Recently, two TdV-LBCbarr genomes, which share sequence identity with ScV-LBC counterparts, were characterized by high-throughput sequencing (HTS). They also share some similar characteristics with Sc-LA viruses. This may explain why TdV-LBCbarr has helper capability to maintain M viruses, whereas ScV-LBC does not. We here analyze two stretches with low sequence identity (LIS I and LIS II) that were found in TdV-LBCbarr Gag-Pol proteins when comparing with the homologous regions of ScV-LBC. These stretches may result from successive nucleotide insertions or deletions (indels) that allow compensatory frameshift events required to maintain specific functions of the RNA-polymerase, while modifying other functions such as the ability to bind V-M (+)RNA for packaging. The presence of an additional frameshifting site in LIS I may ensure the synthesis of a certain amount of RNA-polymerase until the new compensatory indel appears. Additional 5′- and 3′-extra sequences were found beyond V-LBC canonical genomes. Most extra sequences showed high identity to some stretches of the canonical genomes and can form stem-loop structures. Further, the 3′-extra sequence of two ScV-LBC genomes contains rRNA stretches. The origin and possible functions of these extra sequences are here discussed.

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Deep Insertion, Deletion, and Missense Mutation Libraries for Exploring Protein Variation in Evolution, Disease, and Biology

Macdonald

Nedrud

Grimes

et al. 2022

Preprint

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Insertions and deletions (indels) are a major source of genetic variation in evolution and the cause of nearly 30 percent of Mendelian disease. Despite their importance, indels are left out of nearly every systematic mutational scan to date due to technical challenges associated with making indel-containing libraries, limiting our understanding of indels in disease, biology, and evolution. Here we present a library generation method, DIMPLE, that generates deletions, insertions, and missense at similar frequencies within any gene. To benchmark DIMPLE, we generated libraries within four genes (Kir2.1, VatD, TRPV1, and OPRM1) of varying length and evolutionary origin. DIMPLE produces libraries that are near complete, low cost, and low bias. We measured how missense mutations and indels of varying length impact the potassium channel Kir2.1 surface expression. Across all secondary structure, deletions are more disruptive than insertions, beta sheets are extremely sensitive to large deletions, and flexible loops allow insertions far more frequently than deletions. DIMPLE has low bias, ease of use, and low cost will enable high throughput probing of the importance of indels in disease and evolution.

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Rapid protein sequence evolution via compensatory frameshift is widespread in RNA virus genomes

Cited by 9 publications

References 58 publications

Frameshift Mutations in the Microevolution and Macroevolution of Viruses

Frameshift Mutations in the Microevolution and Macroevolution of Viruses

New Insights into the Genome Organization of Yeast Double-Stranded RNA LBC Viruses

Deep Insertion, Deletion, and Missense Mutation Libraries for Exploring Protein Variation in Evolution, Disease, and Biology

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