Evidence map›Paper›PMID 34427640›Full record

ArticleGenome biology and evolution2021

Causes and Consequences of Purifying Selection on SARS-CoV-2.

Atahualpa Castillo Morales, Alan M Rice, Alexander T Ho, Christine Mordstein, Stefanie Mühlhausen, Samir Watson, Laura Cano, Bethan Young, Grzegorz Kudla, Laurence D Hurst

Open access · goldAbstract read
In one paragraph

Article in Genome biology and evolution, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.9field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 48 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 2 countries.

Atahualpa Castillo MoralesThe Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, United Kingdom.
Alan M RiceThe Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, United Kingdom.
Alexander T HoThe Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, United Kingdom.
Christine MordsteinThe Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, United Kingdom.
Stefanie MühlhausenThe Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, United Kingdom.
Samir WatsonDepartment of Molecular Biology and Genetics, Aarhus University, Denmark.
Laura CanoMRC Human Genetics Unit, Institute for Genetics and Molecular Medicine, The University of Edinburgh, United Kingdom.
Bethan YoungThe Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, United Kingdom.
Grzegorz KudlaMRC Human Genetics Unit, Institute for Genetics and Molecular Medicine, The University of Edinburgh, United Kingdom.
Laurence D HurstThe Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, United Kingdom.ORCID 0000-0002-1002-1054
University of Bath · GBInstitute of Genetics and Cancer · GBAarhus University · DK

Funding

Wellcome Trust
6 · The paper itself

Abstract

Owing to a lag between a deleterious mutation's appearance and its selective removal, gold-standard methods for mutation rate estimation assume no meaningful loss of mutations between parents and offspring. Indeed, from analysis of closely related lineages, in SARS-CoV-2, the Ka/Ks ratio was previously estimated as 1.008, suggesting no within-host selection. By contrast, we find a higher number of observed SNPs at 4-fold degenerate sites than elsewhere and, allowing for the virus's complex mutational and compositional biases, estimate that the mutation rate is at least 49-67% higher than would be estimated based on the rate of appearance of variants in sampled genomes. Given the high Ka/Ks one might assume that the majority of such intrahost selection is the purging of nonsense mutations. However, we estimate that selection against nonsense mutations accounts for only ∼10% of all the "missing" mutations. Instead, classical protein-level selective filters (against chemically disparate amino acids and those predicted to disrupt protein functionality) account for many missing mutations. It is less obvious why for an intracellular parasite, amino acid cost parameters, notably amino acid decay rate, is also significant. Perhaps most surprisingly, we also find evidence for real-time selection against synonymous mutations that move codon usage away from that of humans. We conclude that there is common intrahost selection on SARS-CoV-2 that acts on nonsense, missense, and possibly synonymous mutations. This has implications for methods of mutation rate estimation, for determining times to common ancestry and the potential for intrahost evolution including vaccine escape.

Indexed as

MutationCodon, NonsenseCodon UsageCOVID-19Evolution, MolecularHumansModels, GeneticMutation, MissenseMutation RatePolymorphism, Single NucleotideSARS-CoV-2Selection, GeneticSilent MutationCodon, Nonsensecodon usagemutation ratepurifying selectionSARS-CoV-2

Identifiers

PMID34427640
PMCPMC8504154
OpenAlexW3194208617

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.