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The lumpy skin disease virus (LSDV), which mostly affects ruminants and causes huge-economic loss, was endemic in Africa, caused outbreaks in the Middle East, and was recently detected in Russia, Serbia, Greece, Bulgaria, Kazakhstan, China, Taiwan, Vietnam, Thailand, and India. However, the role of evolutionary drivers such as codon selection, negative/purifying selection, APOBEC editing, and genetic variations such as frameshift and in-frame nonsense mutations in the LSDVs, which cause outbreaks in cattle in various countries, are still largely unknown. In the present study, a frameshift mutation in LSDV035, LSDV019, LSDV134, and LSDV144 genes and in-frame non-sense mutations in LSDV026, LSDV086, LSDV087, LSDV114, LSDV130, LSDV131, LSDV145, LSDV154, LSDV155, LSDV057, and LSDV081 genes were revealed among different clusters. Based on the available complete genome sequences, the prototype wild-type cluster-1.2.1 virus has been found in other than Africa only in India, the wild-type cluster-1.2.2 virus found in Africa were spread outside Africa, and the recombinant viruses spreading only in Asia and Russia. Although LSD viruses circulating in different countries form a specific cluster, the viruses detected in each specific country are distinguished by frameshift and in-frame nonsense mutations. Furthermore, the present study has brought to light that the selection pressure for codons usage bias is mostly exerted by purifying selection, and this process is possibly caused by APOBEC editing. Overall, the present study sheds light on microevolutions in LSDV, expected to help in future studies towards disturbed ORFs, epidemiological diagnostics, attenuation/vaccine reverts, and predicting the evolutionary direction of LSDVs.

ABSTRACT DNA replication is a standard and essential function among DNA viruses; however, this functional domain's common ancestor, origin, and evolutionary path in invertebrate- and vertebrate-infecting viruses are not yet fully understood. Here, we present evidence, using a combination of phylogenetic relationships, coevolution, and CLANS (cluster analysis of sequences) analysis, that the parvo-NS1 domain (nonstructural protein NS1, DNA helicase domain) of these DNA viruses that infect vertebrates potentially originated from the invertebrate (Platyhelminthes) parvo-NS1 domain of parvovirus-related sequences (PRSs). Our results suggest that papillomaviruses and the parvovirus subfamilies Densovirinae and Hamaparvovirinae DNA helicase evolved directly from the Platyhelminthes NS1 domain (PRSs). Similarly, the parvovirus subfamily Parvovirinae NS1 domain displayed evolutionary heritage from the PRSs through Hamaparvovirinae. Further, our analysis also clarified that herpesviruses and adenoviruses independently obtained the parvo-NS1 domain from Dependoparvovirus (Parvovirinae). Furthermore, virus-host coevolution analysis revealed that the parvovirus NS1 domain has coevolved with hosts, from flatworms to humans, and it appears that the papillomavirus may have obtained the DNA helicase during the early stages of parvovirus evolution and later led to the development of the DNA helicase of adomavirus and polyomavirus. Finally, herpesviruses and adenoviruses likely inherited the parvo-NS1 domain from Dependoparvovirus in the later stages of evolution. To the best of our knowledge, this is the first evolutionary evidence to suggest that the DNA helicase of viruses that infect vertebrates originated from the invertebrate PRSs. IMPORTANCE DNA replication of DNA viruses is an essential function. This allows DNA replication of viruses to form virus particles. The DNA helicase domain is responsible for this primary function. This domain is present in parvoviruses, papillomaviruses, polyomaviruses, herpesviruses, and adenoviruses. But little is known about the common ancestor, origin, and evolutionary path of DNA helicase in invertebrate- and vertebrate-infecting viruses. Here, we report the possibility of the origin of DNA viruses (DNA helicase) infecting vertebrates from Platyhelminthes (invertebrate) PRSs. Our study established that the parvovirus subfamily Parvovirinae NS1 domain displayed evolutionary heritage from the Platyhelminthes PRSs through Hamaparvovirinae. Furthermore, our study suggests that the papillomavirus DNA helicase may have evolved in the early stages of parvovirus evolution and then led to the development of the adomavirus and polyomavirus. Our study suggests that the herpesviruses and adenoviruses likely inherited the parvo-NS1 domain through gene capture from Dependoparvovirus in the later stages of parvovirus evolution in their hosts.

Monkeypox virus (MPXV) causing multi-country outbreak-2022 is related to viruses caused outbreak-2017–2018 in West Africa. Still not fully understood which proteins of the MPXV discovered in Nigeria in 2017 have mutated through different lineages to the extent that it could cause a multi-country outbreak in 2022; similarly, codon usage bias, host adaptation indices, and the role of selection or mutation pressure in the mutated genes are also not fully studied. Here we report that according to the available sequence data this monkeypox virus acquires point mutations in multiple proteins in each period, and these point mutations accumulate and become a virus that can root outbreak-2022. Viruses exported from Nigeria to Singapore, Israel, and the United Kingdom in 2018–2019 were developed as evolutionary ancestors to B.1 viruses (MPXVs causing multi-country outbreak-2022) through MPXV/United States/2021/MD virus. Although these exported viruses have different amino acid mutations in different proteins, amino acid mutations in 10 proteins are common among them. The MPXV-United Kingdom-P2 virus evolved with only mutations in these 10 proteins and further evolved into MPXV/United States/2021/MD with amino acid mutations in 26 (including amino acid mutations in 10 proteins of the MPXV-United States-P2) proteins. It is noteworthy that specific amino acid mutations in these 22/26 (presence in MPXV/United States/2021/MD) proteins are present in B.1 viruses. Further, analysis of Relative Synonymous Codon Usage (RSCU), Synonymous Codon Usage Fraction (SCUF), and Effective Number of Codons (ENc) revealed codon usage bias in genes that exhibited nucleotide mutations in lineage B.1. Also, host adaptation indices analyzes such as Codon Adaptation Index (CAI), Expected-CAI (eCAI), Relative Codon Deoptimization Index (RCDI) and Expected value for the RCDI (eRCDI) analyzes reveal that the genes that demonstrated nucleotide mutations in lineage B.1 are favorable for human adaptation. Similarly, ENc-GC3s plot, Neutrality plot, and Parity Rule 2 (PR2)-bias plot analyzes suggest a major role of selection pressure than mutation pressure in the evolution of genes displaying nucleotide mutations in lineage B.1. Overall, from 2017 to 2022, MPXV’s mutation and spread suggests that this virus continues to evolve through point mutation in the genes according to the available sequence data.