Final essay
Theme
What is the role of viral recombination in the origin of SARS-CoV-2?
General outline
What is viral recombination?
1. Topic sentence. A brief and summarized definition. "Recombination occurs when at least two viral genomes coinfect the same host cell and exchange genetic segments." (Pérez-Losada et al., 2014)
2. Types of recombination (homologous and non-homologous).
3. Implications on viruses genetic diversity and evolution (see Pérez-Losada et al., 2014).
- Genetic diversity increases.
- Evolution: expansion of viral host ranges, emergence of new viruses, alteration of transmission vector specificities, increases in virulence and pathogenesis, modification of tissue tropisms, evasion of host immunity, and evolution of resistance to antivirals.
4. Does recombination vary across different viruses?
5. Is it common among coronaviruses?
When do phylogenetic reconstructions offer clues about viral recombination events?
1. Trees with different genes showing different relationships?
- "The phylogenies within R1, R2, and R4 indicate that SARS-CoV-2 is most similar to the corresponding regions of the bat coronavirus RaTG13 (Fig. 2a). Interestingly, in all three regions, a coronavirus sampled from a pangolin in 2019 (referred to as “Pangolin Guangdong 2019” in Fig. 2, following Boni et al., 2020) shows a close phylogenetic relationship to the common ancestor of SARS-CoV-2 and RaTG13 (Fig. 2a32). Region 3 (R3) in Fig. 2a includes the variable loop region of the SARS-CoV-2 S protein, which is 222 bp in length and contains 6 residues of the RBD. Remarkably, this region shares the closest similarity with the pangolin coronavirus strain, rather than with RaTG1328,32 (Fig. 2a)." (Singh & Yi, 2021)
(Figure 1: phylogenetic tree of betacoronaviruses with indications of viral recombination events)
Which viral recombination events have probably occurred in the evolutionary history of the SARS-CoV-2?
(Perhaps, this part can be merged with the previous one. While writing about phylogenetic reconstructions and viral recombination events, I can detail with the SARS-CoV-2 example)
Recombination between bat and pangolin coronaviruses? (Remember that this is a hypothesis. Another possibility is the independent origin.)
- "The variable loop region of the S protein shows a unique evolutionary history compared to the rest of the S protein and the SARS-CoV-2 genome overall, consistent with two different scenarios (Fig. 2b): first, after the lineages leading to the SARS-CoV-2 and RaTG13 split, a recombination event between the SARS-CoV-2 lineage and the Pangolin Guangdong 2019 lineage resulted in the acquisition of new RBD residues (Fig. 2b, left panel). A second scenario is that recombination with the Pangolin Guangdong 2019 lineage occurred in the common ancestral lineage of SARS-CoV-2 and RaTG13." (Singh & Yi, 2021)
Extensive recombination in the betacoronaviruses evolution makes standard phylogenetic reconstructions based on full genomes problematic (see Li et al. 2020).
Why were these events important for the evolutionary origin of SARS-CoV-2?
(Figure 2: how does the receptor binding motif is related to the capacity to infect humans?)
Acquisition of receptor binding motif through recombination?
Practical implications
Definitions
RBM: receptor binding motif
RBD: receptor binding domain
ORF: open reading frames
Inserting content
First paragraph
Viral recombination is the exchange of genetic segments when at least two viral genomes coinfect the same host cell (Pérez-Losada et al., 2014).
In viruses, the term recombination does not mean the same as it does in diploid, sexually reproducing organisms.
In the latter, recombination is the reciprocal exchange of genetic material between chromatids, while in viruses the receiver of the genetic segment usually does not act as a donor (non-reciprocal exchange) (Pérez-Losada et al., 2014).
[HOW OFTEN DOES THIS PROCESS OCCUR?]
Recombination facilitates the emergence of evolutionary innovations (REFS), leading to increases in virulence and pathogenesis, evasion of host immunity, and expansion of viral host ranges (REFS).
Thus, recombination plays a major role in the evolutionary history of viruses.
Second paragraph
Although phylogenetic reconstructions are not explicit tests for recombination, they may offer clues about this process.
Viral recombination events lead to phylogenetic trees that show different evolutionary relationships depending on the genetic sequence taken into account.
In the case of SARS-CoV-2, for example, all phyogenetic trees show that SARS-CoV-2 is more closely related to RaTG13 than to any other group.
The exception for this is the phylogenetic tree based on genetic sequence corresponding to the variable loop region of the S protein, which shows Pangolin Guangdong 2019 as the closest group.
(Figure 1. Multiple trees)
Third paragraph
This indicates that an event of viral recombination with Pangolin Guangdong 2019 might have occurred in the evolutionary history of SARS-CoV-2.
The phylogenetic trees of SARS-CoV-2 are consistent with two different scenarios.
In the first scenario, recombination occurred after the lineage leading to SARS-CoV-2 and RaTG13 split.
In this case, a recombination event took place between SARS-CoV-2 and Pangolin Guangdong 2019.
In the second scenario, recombination occurred before the lineage leading to SARS-CoV-2 and RaTG13 split.
In this case, a recombination event took place between Pangolin Guangdong 2019 and the common ancestral lineage of SARS-CoV-2 and RaTG13.
Fourth paragraph
The recombination event between SARS-CoV-2 and Pangolin Guangdong 2019 was probably crucial in the evolutionary history of SARS-CoV-2.
The genetic sequence acquired from Pangolin Guangdong 2019 by SARS-CoV-2 correspond to the receptor-binding domain (RBD) of the spike glycoprotein (S protein) (Zhu et al., 2020).
This might have resulted in the adaption of SARS-CoV-2 to human hosts, thus originating the ongoing pandemic.
Conclusion
Understanding the potential of viruses to suffer recombination is crucial to
Final version
Viral recombination is the exchange of genetic segments when at least two viral genomes coinfect the same host cell (Pérez-Losada et al., 2014). In viruses, the term recombination does not mean the same as it does in diploid, sexually reproducing organisms. In the latter, recombination is the reciprocal exchange of genetic material between chromatids, while in viruses the receiver of the genetic segment usually does not act as a donor (non-reciprocal exchange) (Pérez-Losada et al., 2014). Recombination facilitates the emergence of evolutionary innovations (Leveufre et al., 2009), leading to increases in virulence and pathogenesis, evasion of host immunity, and expansion of viral host ranges (Martin et al., 2011; Simon-Loriere and Holmes, 2011). Viral recombination rates are particularly high in some groups such as retroviruses (ssRNA-RT) (e.g., Jetzt et al., 2000) and SARS-like coronaviruses (Bobay et al., 2020). Thus, recombination plays a major role in viral evolution.
Although phylogenetic reconstructions are not explicit tests for recombination, they offer important clues about this process. Viral recombination events lead to phylogenetic trees that show different evolutionary relationships depending on the genetic sequence that is taken into account (Singh & Soojin, 2021). Phylogenetic trees of some coronaviruses, for example, show that SARS-CoV-2 (the human strain responsible for the ongoing pandemic) is more closely related to RaTG13 (a bat strain) than to any other group. The exception for this is the phylogenetic tree based on the genetic sequence corresponding to the variable loop region of the spike glycoprotein (S protein), which shows that Pangolin Guangdong 2019 (a pangolin strain) is the closest related group (Figure 1).
Figure 1. Phylogenetic trees based on multiple genetic sequences of coronaviruses, including strains from pangolins (Pangolin Guangdong 2019), bats (RaTG13, Bat-SL-CoV, Rs3367), palm civets (PC4-13), and humans (SARS-CoV-2 and Tor-2). In region 1 (R1), region 2 (R2), and region 4 (R4), the closest relative of SARS-CoV-2 is the bat
coronavirus RaTG13. In region 3 (R3), SARS-CoV-2 and the pangolin strain of coronavirus (Pangolin Guangdong 2019) are more closely related. Source: Singh & Soojin, 2021.
This pattern indicates that an event of viral recombination with Pangolin Guangdong 2019 might have occurred in the evolutionary history of SARS-CoV-2. Two different scenarios hypothesize the evolutionary timing of the recombination event that might have introduced a pangolin coronavirus sequence into SARS-CoV-2. In the first scenario, recombination might have occurred after the lineage leading to SARS-CoV-2 and RaTG13 split. In this case, a recombination event took place between SARS-CoV-2 and Pangolin Guangdong 2019. In the second scenario, recombination occurred before the divergence between SARS-CoV-2 and RaTG13. If so, a recombination event occurred between Pangolin Guangdong 2019 and the common ancestral lineage of SARS-CoV-2 and RaTG13 (Figure 2) (Singh & Soojin, 2021).
Figure 2. Two possible recombination scenarios may have introduced the region 3 of the pangolin coronavirus Pangolin Guangdong 2019 into the SARS-CoV-2 genome. In scenario I, after the split of SARS-CoV-2 and RaTG13, recombination might have occurred between SARS-CoV-2 and Pangolin Guangdong 2019. In scenario II, recombination probably occurred between the pangolin (Pangolin Guangdong 2019) lineage and the common ancestral lineage of SARS-CoV-2 and RaTG13. This was probably followed the accumulation of mutations in the RaTG13 lineage, splitting RaTG13 and SARS-CoV-2 into two different strains.
The putative recombination event between SARS-CoV-2 and Pangolin Guangdong 2019 was probably critical in the evolutionary history of SARS-CoV-2. The genetic sequence acquired from Pangolin Guangdong 2019 by SARS-CoV-2 correspond to the receptor-binding domain (RBD) of the S protein (Zhu et al., 2020). This might have resulted in the adaption of SARS-CoV-2 to human hosts, thus initiating the ongoing pandemic. Previous disease outbreaks caused by coronaviruses (SARS and MERS) have also had a zoonotic origin (Dudas et al., 2018). This repetitive pattern of the introduction of animal viruses into human populations, probably due to recombination events, suggests that future pandemics are inevitable (Singh & Soojin, 2021). However, phylogenetic reconstructions can help us to be prepared for future outbreaks, as they offer clues about viral recombination events. This improves our knowledge on the origin of viral lineages, and thus may accelerate the development of new drugs and vaccines.
References
Bobay, L. M., O’Donnell, A. C., & Ochman, H. (2020). Recombination events are concentrated in the spike protein region of Betacoronaviruses. PLoS genetics, 16(12), e1009272.
Dudas, G., Carvalho, L. M., Rambaut, A., & Bedford, T. (2018). MERS-CoV spillover at the camel-human interface. elife, 7, e31257.
Jetzt, A. E., Yu, H., Klarmann, G. J., Ron, Y., Preston, B. D., & Dougherty, J. P. (2000). High rate of recombination throughout the human immunodeficiency virus type 1 genome. Journal of virology, 74(3), 1234-1240.
Lefeuvre, P., Lett, J. M., Varsani, A., & Martin, D. P. (2009). Widely conserved recombination patterns among single-stranded DNA viruses. Journal of virology, 83(6), 2697-2707.
Martin, D. P., Biagini, P., Lefeuvre, P., Golden, M., Roumagnac, P., & Varsani, A. (2011). Recombination in eukaryotic single stranded DNA viruses. Viruses, 3(9), 1699-1738.
Pérez-Losada, M., Arenas, M., Galán, J. C., Palero, F., & González-Candelas, F. (2015). Recombination in viruses: mechanisms, methods of study, and evolutionary consequences. Infection, Genetics and Evolution, 30, 296-307.
Simon-Loriere, E., & Holmes, E. C. (2011). Why do RNA viruses recombine?. Nature Reviews Microbiology, 9(8), 617-626.
Singh, D., & Soojin, V. Y. (2021). On the origin and evolution of SARS-CoV-2. Experimental & Molecular Medicine, 53(4), 537-547.
Zhu, Z., Meng, K., & Meng, G. (2020). Genomic recombination events may reveal the evolution of coronavirus and the origin of SARS-CoV-2. Scientific reports, 10(1), 1-10.
Autoavaliação
A disciplina atendeu às minhas expectativas. Considero que fui introduzido a conceitos importantes da evolução molecular. Mesmo que estes tenham sido discutidos de maneira relativamente superficial, conheci a literatura canônica sobre diversos temas.
Quanto à minha atuação na disciplina, considero que tenha sido ótima. Trabalhei tanto no horário dedicado às leituras e atividades, quanto em meu tempo livre. Esforcei-me para participar das discussões e para desenvolver as atividades de escrita da melhor maneira possível. Porém, na última semana do curso senti certa exaustão, o que acredito ter prejudicado meu desempenho no ensaio final. Atribuo esse cansaço ao caráter condensado da disciplina e a alguns problemas pessoais com os quais tive de lidar paralelamente. Assim considero que tenha me dedicado ao máximo dentro de minhas limitações.
Autoavaliação: 1