Phylodynamic analysis of the monkeypox virus genome suggests low genetic variation and evolutionary rates

By Dr. Chinta SidharthanReviewed by Aimee MolineuxNov 7 2022

In a recent study published in the Journal of Clinical Medicine, researchers explored the genetic variability among the monkeypox virus genomes of Clade IIb lineage B.1 using a phylodynamic and genetic survey to confirm the epidemic cluster in the clade and understand the evolution of the virus.

Background

The etiological agent of monkeypox is a zoonotic, double-stranded deoxyribonucleic acid (DNA) virus called the monkeypox virus, which belongs to the same family (Poxviridae) as the causative agent of smallpox. Until recently, the disease was endemic to central and western Africa, with the monkeypox viruses forming two clades — the Congo Basin or Central African clade (Clade I) and the West African clade (Clade II).

The 2022 outbreak of monkeypox outside the endemic regions has been attributed to the Clade II monkeypox viruses, which are less virulent and severe, as evidenced by the lower death rate compared to infections with Clade I viruses. However, given the rapid spread of the disease in non-endemic regions, it is important to monitor the genetic variation within the clade.

About the study

The present study used 1271 monkeypox virus whole genomes accessed through the Global Initiative on Sharing Avian Influenza Data (GISAID) database. The sequences were aligned using Multiple Alignment with Fast Fourier Transform (MAFFT). The Pairwise Homoplasy Index or PHI (Φ) test was used to circumvent bias due to recombination or indels.

A fixed evolutionary rate implemented in the Bayesian Evolutionary Analysis by Sampling Trees (BEAST) software was used to reconstruct the population dynamics within the monkeypox genomes. The researchers also performed a tip-to-root regression on a maximum likelihood phylogeny to verify its temporal signals. Additionally, genetic epidemiology was reconstructed.

Results

The results from the Φ test indicated an absence of recombination, insertion, or deletion events and reported all the pairwise analyzed parsimony informative sites to be compatible. The Bayesian Skyline Plot indicated no major changes in genetic variability between samples collected in early May 2022 and late August of the same year. However, the genetic variability then showed a slight decrease and then an increase, reaching a plateau in September 2022.

The authors noted that the genetic variability trend shown by the monkeypox virus was in contrast to the trend of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which mutated rapidly during the coronavirus disease 2019 (COVID-19) pandemic.

The genetic variability changes seen in the monkeypox virus explained the slow population size growth rate. The phylogenomic reconstruction displayed small independent clusters, with some specimens common to two clusters. However, the overall reconstruction pattern allowed the clusters to be correlated to specific geographical areas of origin. Furthermore, the few localized clusters that did emerge did not seem to have any descendants and were evolutionarily blind lineages.

Additionally, the tip-to-root regression analysis indicated no correlation between the sampling dates and sequence divergence, indicating low genetic variability. DNA viruses are known to evolve slower than ribonucleic acid (RNA) viruses, causing the evaluation of divergence concerning time difficult. However, there do exist DNA viruses, such as the herpesviruses, that exhibit comparable genetic variability as RNA viruses. Still, the monkeypox virus lacks the high mutation rate needed for increased genetic variability.

From the perspective of human health, the low genetic variability of the monkeypox virus presents an advantage as it limits the spread of the disease. The authors cautioned that despite lower evolutionary rates than other viruses such as SARS-CoV-2, the monkeypox virus lineage B.1 is evolving faster than the other lineages, and genomic surveillance of monkeypox clusters is essential to keep the disease in check.

Conclusions

To summarize, the study used published whole genome sequences of the monkeypox virus to explore the genetic variation and phylogenomic patterns within the Clade IIb lineage B.1. The results suggested low genetic variability and evolutionary rates among the epidemic cluster from the 2022 outbreak, which could be attributed to the slow evolution of DNA viruses.

However, the authors believe that the reduced virulence and severity and the low genetic variation do not imply a less cautious approach to the current monkeypox outbreak. Monitoring the genetic variations within the monkeypox virus clusters is imperative in limiting the spread of the disease.