Yufei, J. | bioRxiv Science

bioRxiv2022

Origins of monkeypox viruses and their strains circulating in 2022

Monkeypox has spread unprecedentedly to nearly 100 countries and infected more than 51,000 people since 1 May 2022. This large-scale outbreak constituted a public health emergency of international concern (PHEIC), as declared by the World Health Organization. To better recognize and control this outbreak, we explore here through phylogenetic analysis the origins of MPXVs and their strains circulating in 2022, which remain unclear so far. Our results suggest that MPXVs possibly originated from some cowpox viruses and three lineages of MPXVs within Clade IIb circulated in 2022. Our results also suggest that two MPXVs respectively similar to the two MPXVs exported from Nigeria to the USA in 2021, ON676708/USA/2021 and ON676707/USA/2021, evolved into two lineages and sparked the large-scale outbreak in 2022, after their unknown evolutionary and epidemiological journeys possibly in Nigeria, the USA, or other countries before May 2022. This view does not stigmatize any country, because monkeypox is an endemic zoonosis in west Africa with wildlife reservoirs, and its large-scale outbreak in 2022 also resulted from the global decline of population immunity against smallpox due to the cease of vaccination against smallpox decades ago.

microbiology↗

bioRxiv2022

Frequencies and Features of Frameshift Mutations in Microevolution and Macroevolution of Viruses

Some nucleotide insertions or deletions (indels) in open reading frames of virus genes lead to frameshift mutations (FSMs), which can drastically change amino acid sequences. Most FSMs are deleterious and inhibited by natural selection, but some FSMs could aid viruses in adapting to new hosts, escaping immunity, or changing viral pathogenicity or transmissibility. Surprisingly, various fundamental aspects of FSMs in virus evolution remain unknown. In this report, we identified 679 FSMs in the genomes of viruses from 13 randomly selected animal virus families using randomly selected sequences. The 679 FSMs were formed with 1-5 indels, and most (89.4%) FSMs were fixed through the compensatory mechanism with two indels. Each FSM changed 3-209 (mean=15.4, median=13) amino acid residues. FSM frequencies were usually higher in viral sequences with lower sequence identities and steeply increased when sequence identities declined to 60.0%-69.9% or 70.0%-79.9%. This suggests that FSMs are more important to the macroevolution (i.e., inter-species evolution, including speciation) than to the microevolution (i.e., intra-species evolution) of viruses. This study provided novel evidence for the hopeful monster hypothesis in evolutionary biology. Furthermore, we found that FSMs occurred at different frequencies among genes in the same virus genomes and among virus families. Collectively, this study revealed multiple fundamental features of FSMs in virus evolution for the first time and provided novel insights into the mechanisms of macroevolution and speciation.

evolutionary biology↗