Network of co-mutations in Ebola virus genome predicts the disease lethality

Deng, Lizong; Liu, Mi; Hua, Sha; Peng, Yousong; Wu, Aiping; Qin, F. Xiao-Feng; Cheng, Genhong; Jiang, Taijiao

doi:10.1038/cr.2015.54

Cited by 18 publications

(20 citation statements)

References 9 publications

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“…We show that GP forms a major node of comutation network for EBOV evolution, one of the key contributing factors to its case fatality rate, i.e. the pathogenicity power of the virus [10]. Furthermore, the study has also revealed a high degree of connectivity of GP with the viral NP and L proteins in the comutation network, which is entirely unexpected, suggesting potentially important functional relevance [10].…”

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confidence: 88%

“…the pathogenicity power of the virus [10]. Furthermore, the study has also revealed a high degree of connectivity of GP with the viral NP and L proteins in the comutation network, which is entirely unexpected, suggesting potentially important functional relevance [10]. Experiments are under the way in testing whether paired comutations are involved in physical interactions and whether such interactions can be exploited for drug targeting to control viral infection, replication or pathogenesis.…”

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confidence: 99%

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New targets for controlling Ebola virus disease

Qin

Jiang

et al. 2015

National Science Review

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confidence: 88%

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confidence: 99%

New targets for controlling Ebola virus disease

Qin

Jiang

et al. 2015

National Science Review

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“…There are previous studies which have used genomic co-mutations as a basis of the evolution of human H3N2 and Ebola viruses (Du, et al, 2008;Deng, et al, 2015). These viral genome models have identified the co-mutating nucleotide clusters, apparently underpinning the dynamics of virus evolution since these clusters were antigenic regions of the viral capsid proteins (Du, et al, 2008;Deng, et al, 2015). In another study, Shinde et al demonstrated the impact of codon position bias while forming co-mutations using human mt-genomes.…”

Section: Introductionmentioning

confidence: 99%

Impact of modular mitochondrial epistatic interactions on the evolution of human subpopulations

Shinde

Whitwell

Verma

et al. 2018

Preprint

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Investigation of human mitochondrial (mt) genome variation has been shown to provide insights to the human history and natural selection. By analyzing 24,167 human mt-genome samples, collected for five continents, we have developed a co-mutation network model to investigate characteristic human evolutionary patterns. The analysis highlighted richer co-mutating regions of the mt-genome, suggesting the presence of epistasis. Specifically, a large portion of COX genes was found to co-mutate in Asian and American populations, whereas, in African, European, and Oceanic populations, there was greater comutation bias in hypervariable regions. Interestingly, this study demonstrated hierarchical modularity as a crucial agent for these co-mutation networks. More profoundly, our ancestry-based co-mutation module analyses showed that mutations cluster preferentially in known mitochondrial haplogroups. Contemporary human mt-genome nucleotides most closely resembled the ancestral state, and very few of them were found to be ancestral-variants. Overall, these results demonstrated that subpopulation-based biases may favor mitochondrial gene specific epistasis.

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“…In biological networks, they represent meaning to protein family as well as to pathway conservation 16 which has been shown theoretically and experimentally as well 17 . Furthermore despite the tremendous advancements in the field of network theory, very few have taken nucleotide based genomic co-occurrences into consideration 18,19 whereas codon based genomic co-occurrences have not been described previously to the best our knowledge. Co-occurrences of codon and non-codon positions between the genomes across sub-populations is expected to help in gaining insights into co-changes in genomes as well as conservation of these co-changes across sub-populations since these co-changes are said to be largely dispositioned during evolutionary events such as climatic changes, migration events, genetic traits etc 20 .…”

Section: Introductionmentioning

confidence: 99%

Codon based co-occurrence network motifs in human mitochondria

Shinde

Sarkar

Jalan

2016

Preprint

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The nucleotide polymorphism in the human mitochondrial genome (mtDNA) tolled by codon position bias plays an indispensable role in human population dispersion and expansion. Herein, genome-wide nucleotide co-occurrence networks were constructed using data comprised of five different geographical regions and around 3000 samples for each region. We developed a powerful network model to describe complex mitochondrial evolutionary patterns among codon and noncodon positions. We found evidence that the evolution of human mitochondria DNA is dominated by adaptive forces, particularly mutation and selection, which was supported by many previous studies. The diversity observed in the mtDNA was compared with mutations, co-occurring mutations, network motifs considering codon positions as causing agent. This comparison showed that longrange nucleotide co-occurrences have a large effect on genomic diversity. Most notably, codon motifs apparently underpinned the preferences among codon positions for co-evolution which is probably highly biased during the origin of the genetic code. Our analysis also showed that variable nucleotide positions of different human sub-populations implemented the independent mtDNA evolution to its geographical dispensation. Ergo, this study has provided both a network framework and a codon glance to investigate co-occurring genomic variations that are critical in underlying complex mitochondrial evolution. "Nature's stern discipline enjoins mutual help at least as often as warfare. The fittest may also be the gentlest. " as proclaimed by Theodosius Dobzhansky on mankind evolution, like galaxy formations, the evolution of human remains the generation long grit of thinkers. Non-recombining loci, such as the maternally inherited mitochondrial DNA have been known to provide a richer estimation insight into ancestral human genetic variations during evolution 1 . Mitochondrial DNA is highly polymorphic, and its diverse nature in humans may contribute to individual differences in function 2,3 . Sequence variations considered in human mtDNA are selectively neutral 4 . Under this assumption, the pool of mutations that enter a population and are subsequently fixed by the selection or by the stochastic process of genetic drift will differ across populations 5,6 . Conversely, mtDNA polymorphism might also have been shaped via positive selection because of mito-nuclear co-evolution 7 . The evidence in support of mtDNA sequence polymorphism affecting phenotypic variation in metabolism, life-history traits and fitness is compelling 8 . In retrospect, several studies were carried out that highlighted the role of natural selection and genetic drift on the diversity and divergence of mtDNA 2 . The methods based on phylogenetics, distances among sequences and clustering have successfully classified various traits and migrational events in human population 9 . Furthermore, genome wide studies and mapping techniques, such as quantitative trait loci and linkage disequilibrium have effectively sorted genes and alleles ...

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Network of co-mutations in Ebola virus genome predicts the disease lethality

Cited by 18 publications

References 9 publications

New targets for controlling Ebola virus disease

New targets for controlling Ebola virus disease

Impact of modular mitochondrial epistatic interactions on the evolution of human subpopulations

Codon based co-occurrence network motifs in human mitochondria

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