In a recent study published on the bioRxiv* preprint server, researchers demonstrated the parallel evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Deltacron variant.
Study: Incipient parallel evolution of Deltacron variant SARS-CoV-2 in southern Brazil. Image credit: Andrii Vodolazhskyi/Shutterstock
background
Recombination and gene flow are likely to play a larger role in the adaptive development of SARS-CoV-2 as more people travel internationally and more lineages coexist. This could lead to the beginnings of parallel evolution across multiple recombinant lineages. However, the full extent of SARS-CoV-2 recombinant evolution may be underestimated as it is difficult to detect recombinant lineages.
About the study
In the present study, the researchers evaluated four SARS-CoV-2 recombinants found in southern and southeastern Brazil.
Clinical samples were obtained from three organizations in Rio Grande do Sul, Brazil, that participated in the diagnosis of genomic surveillance of COVID-19 and SARS-CoV-2. In each case, real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to identify SARS-CoV-2 infection before the samples were submitted to the genome sequencing procedure at each institution. . On May 20, 2022, the team noticed a loss of the SARS-CoV-2 spike gene (S) in sample SC2-9898; therefore, this sample was sequenced, followed by library preparation. The CleanPlex human SARS-CoV2 pipeline was used to screen the resulting FASTq files for sequence alignment.
The team performed blast searches of the Global Initiative for Sharing All Influenza Data (GISAID) “unassigned” dataset using the Brazil/RS-FIOCRUZ-8390/2022 sequence to find additional genomes of the new Brazilian recombinant . Subsequently, using the putative Brazilian recombinant sequences as a guide, the team visually examined the mutation pattern corresponding to the top hits in Nextclade Web.
The first alignment step used the MN908947 sequence as a reference. Using Sc2rf, the team evaluated the recombinant genomes. The SARS-CoV-2 Delta and Omicron sections of the genomes from the first sequences of each recombinant lineage were manually segmented. Next, we evaluated the Pangolin lineage corresponding to each segment of the 5′ Delta and 3′ Omicron.
With Pango lineages in mind, the team built lineage-specific databases (GISAID sequences). To identify the top 20 hits from the reference databases, each segment was used as a query. The researchers retrieved their sequences from GISAID after selecting the best parental candidates. Using a Python script, these first-hit sequences were used to determine the mutation frequency for each lineage.
results
The genomic sequence of Cruz Alta (Brazil/RS-FIOCRUZ-8390/2022) was assigned to the XS recombinant lineage by preliminary analysis. However, compared to an XS archetype, the first 20 kb of the genome showed a distinctive mutational pattern.
The team discovered two more sequences that are comparable to the Cruz Alta sequence through routine genomic monitoring of the state of Rio Grande do Sul, one from Porto Alegre (Brasil/SC2-9898/2022) and Santa Maria (Brazil/RS-315-66266). -219/2022). The team also searched the GISAID database and discovered a sequence from Rio de Janeiro (Brazil/RJ-NVBS19517GENOV829190059793/2022) that was strikingly similar to recombinants from southern Brazil.
After classifying the sequences as suspected recombinants, Sc2rf was used to search for possible recombination signals in their genomes. The team found that the 3′ region belonged to an Omicron lineage while the 5′ region belonged to a Delta lineage. Further analysis revealed that the 3′ and 5′ genomic regions mostly resembled AY.101 and BA.1 or BA.1.1, respectively.
In addition, the team created databases for each lineage of sequences and searched them for the most similar sequences in each section (5′ Delta and 3′ Omicron). The mutational signatures of the parental sequences were compared with those of the Brazilian recombinant sequences. All Brazilian recombinant sequences showed the same trends in this analysis: their 3′ section belonged to the BA.1.1 lineage and their 5′ segment matched AY.101.
The four Brazilian recombinant sequences all included the C10604T substitution. As the recombinant discovered in this study met Pango nomenclature standards, it was named AYBA-RS, taking into account its paternal lineages (AY.101 and BA.1.1) and place of origin.
As the four Brazilian recombinant sequences formed a separate group from the other Deltacrons, haplotype network analysis and phylogenetic network reconstruction showed sufficient consistency. In addition, both models showed how the different Deltacrons were split between the Omicron and Delta groups, which contained more of each lineage.
The team calculated that the recombination event that gave rise to the recombinant could have occurred 180 days before the first sample collection date, or December 2021, based on the number of SNPs among the AYBA-RS sequences . Examination of the lineage density plots revealed that AY.101 and BA.1.1 were overlapping in regions of the country, mainly in December 2021. The southern region of Brazil showed higher relative frequencies of AY .101 and BA.1.1 than the rest of Brazil.
The team demonstrated the discovery of the first Brazilian SARS-CoV-2 Deltacron lineage, AYBA-RS. The study showed that this recombinant strain originated in southern Brazil as a result of unique recombination between the AY.101 and BA.1.1 lineages.
*Important news
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice/health-related behavior, or be treated as established information.