Ongoing Recombination in SARS-CoV-2 Revealed through Genealogical Reconstruction

Abstract

The evolutionary process of genetic recombination has the potential to rapidly change the properties of a viral pathogen, and its presence is a crucial factor to consider in the development of treatments and vaccines. It can also significantly affect the results of phylogenetic analyses and the inference of evolutionary rates. The detection of recombination from samples of sequencing data is a very challenging problem, and is further complicated for SARS-CoV-2 by its relatively slow accumulation of genetic diversity. The extent to which recombination is ongoing for SARS-CoV-2 is not yet resolved. To address this, we use a parsimony-based method to reconstruct possible genealogical histories for samples of SARS-CoV-2 sequences, which enables us to pinpoint specific recombination events that could have generated the data. We propose a statistical framework for disentangling the effects of recurrent mutation from recombination in the history of a sample, and hence provide a way of estimating the probability that ongoing recombination is present. We apply this to samples of sequencing data collected in England and South Africa, and find evidence of ongoing recombination.

Recombination patterns in coronaviruses

“…Though not yet highly prevalent, evidence for recombination in SARS-CoV-2 has started to appear (VanInsberghe et al ., 2020; Jackson et al ., 2021; Varabyou et al ., 2021; Ignatieva et al ., 2021). As such, it is crucial to know the extent to which recombination is expected to shape SARS-CoV-2 in the coming years, to have methods to identify recombination and to perform phylogenetic reconstruction in the presence of recombination.…”

Culture and identification of a “Deltamicron” SARS-CoV-2 in a three cases cluster in southern France

“…[10][11][12][13] Furthermore, genetic recombinations were reported or suspected, based on the concurrent detection in consensus genomes of signature mutations of different mutants or variants. 10,12,[14][15][16][17][18][19][20][21][22][23][24] A study detected up to 1,175 (0.2%) putative recombinant genomes among 537,360 genomes and estimated that up to 5% SARS-CoV-2 having circulated in the USA and UK could be recombinants. 16 Two pandemic variants, Delta and Omicron 21K (Nextclade classification 25,26 )/BA.1 (Pangolin classification 27 ), recently succeeded each other as the predominant viruses but cocirculated for a period of several weeks, creating conditions for co-infections and subsequently recombinations.…”

“…Co-infections with two variants were reported including recently with SARS-CoV-2 Delta and Omicron variants (Jackson et al, 2021; Francisco et al, 2021; Taghizadeh et al, 2021; Rockett et al, 2022). Furthermore, genetic recombinations were reported or suspected, based on the concurrent detection in consensus genomes of signature mutations of different mutants or variants (Yi, 2020; Yeh and Contreras, 2020; VanInsberghe et al, 2020; Gallaher, 2020; Jackson et al, 2021; Haddad et al, 2021; Makarenkov et al, 2021; Varabyou et al, 2021; Leary et al, 2021; Taghizadeh et al, 2021; Lohrasbi-Nejad, 2022; Kreier, 2022; Ignatieva et al, 2022). A study detected up to 1,175 (0.2%) putative recombinant genomes among 537,360 genomes from the GISAID database and estimated that up to 5% SARS-CoV-2 having circulated in the USA and UK could be recombinants (VanInsberghe et al, 2020).…”

Emergence of Within-Host SARS-CoV-2 Recombinant Genome After Coinfection by Gamma and Delta Variants: A Case Report

“…Recent studies reported the detection of SARS-CoV-2 recombinant lineages circulating at a low frequency ( 11 , 12 , 18 – 21 ). Nevertheless, these studies were restricted to detecting the inter-host dissemination of genomes post-recombination events, which could be biased by spurious mutations generated due to library preparation, laboratory contamination, and unavailability of raw sequenced data.…”