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@article{Hill:2022:10.1101/2022.03.08.481609,
author = {Hill, V and Du, Plessis L and Peacock, TP and Aggarwal, D and Colquhoun, R and Carabelli, AM and Ellaby, N and Gallagher, E and Groves, N and Jackson, B and McCrone, JT and OToole, Á and Price, A and Sanderson, T and Scher, E and Southgate, J and Volz, E and Barclay, WS and Barrett, JC and Chand, M and Connor, T and Goodfellow, I and Gupta, RK and Harrison, EM and Loman, N and Myers, R and Robertson, DL and Pybus, OG and Rambaut, A},
doi = {10.1101/2022.03.08.481609},
title = {The origins and molecular evolution of SARS-CoV-2 lineage B.1.1.7 in the UK},
url = {http://dx.doi.org/10.1101/2022.03.08.481609},
year = {2022}
}

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TY  - JOUR
AB  - <jats:title>Abstract</jats:title><jats:p>The first SARS-CoV-2 variant of concern (VOC) to be designated was lineage B.1.1.7, later labelled by the World Health Organisation (WHO) as Alpha. Originating in early Autumn but discovered in December 2020, it spread rapidly and caused large waves of infections worldwide. The Alpha variant is notable for being defined by a long ancestral phylogenetic branch with an increased evolutionary rate, along which only two sequences have been sampled. Alpha genomes comprise a well-supported monophyletic clade within which the evolutionary rate is more typical of SARS-CoV-2. The Alpha epidemic continued to grow despite the continued restrictions on social mixing across the UK, and the imposition of new restrictions, in particular the English national lockdown in November 2020. While these interventions succeeded in reducing the absolute number of cases, the impact of these non-pharmaceutical interventions was predominantly to drive the decline of the SARS-CoV-2 lineages which preceded Alpha. We investigate the only two sampled sequences that fall on the branch ancestral to Alpha. We find that one is likely to be a true intermediate sequence, providing information about the order of mutational events that led to Alpha. We explore alternate hypotheses that can explain how Alpha acquired a large number of mutations yet remained largely unobserved in a region of high genomic surveillance: an under-sampled geographical location, a non-human animal population, or a chronically-infected individual. We conclude that the last hypothesis provides the best explanation of the observed behaviour and dynamics of the variant, although we find that the individual need not be immunocompromised, as persistently-infected immunocompetent hosts also display a higher within-host rate of evolution. Finally, we compare the ancestral branches and mutation profiles of other VOCs to each other, and identify that Delta appears to be an outlier
AU  - Hill,V
AU  - Du,Plessis L
AU  - Peacock,TP
AU  - Aggarwal,D
AU  - Colquhoun,R
AU  - Carabelli,AM
AU  - Ellaby,N
AU  - Gallagher,E
AU  - Groves,N
AU  - Jackson,B
AU  - McCrone,JT
AU  - OToole,Á
AU  - Price,A
AU  - Sanderson,T
AU  - Scher,E
AU  - Southgate,J
AU  - Volz,E
AU  - Barclay,WS
AU  - Barrett,JC
AU  - Chand,M
AU  - Connor,T
AU  - Goodfellow,I
AU  - Gupta,RK
AU  - Harrison,EM
AU  - Loman,N
AU  - Myers,R
AU  - Robertson,DL
AU  - Pybus,OG
AU  - Rambaut,A
DO  - 10.1101/2022.03.08.481609
PY  - 2022///
TI  - The origins and molecular evolution of SARS-CoV-2 lineage B.1.1.7 in the UK
UR  - http://dx.doi.org/10.1101/2022.03.08.481609
ER  -

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