ADAR1 can drive Multiple Myeloma progression by acting both as an RNA editor of specific transcripts and as a DNA mutator of their cognate genes

Tasakis, Rafail Nikolaos; Laganà, Alessandro; Stamkopoulou, Dimitra; Melnekoff, David; Nedumaran, Pavithra; Leshchenko, Violetta V.; Pecori, Riccardo; Parekh, Samir; Papavasiliou, F. Nina

doi:10.1101/2020.02.11.943845

Cited by 3 publications

(1 citation statement)

References 61 publications

(35 reference statements)

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“…1 Indications exist that the DNA mutation rate due to RNA editing enzymes, though lower than the RNA editing rate, is still much higher than the human genome-wide average mutation rate (Saraconi et al, 2014;Tasakis et al, 2020).…”

Section: Mutational Replacement Of Rna Editingmentioning

confidence: 99%

Evolutionary Honing in and Mutational Replacement: How Long-Term Directed Mutational Responses to Specific Environmental Pressures Are Possible

Livnat¹,

Melamed²

2022

Preprint

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Recent results have shown that the human malaria-resistant hemoglobin S mutation originates de novo more frequently in the gene and in the population where it is of adaptive significance, namely, in the hemoglobin subunit beta gene compared to the non-resistant but otherwise identical 20A>T mutation in the hemoglobin subunit delta gene, and in sub-Saharan Africans, who have been subject to intense malarial pressure for many generations, compared to Northern Europeans, who have not. This finding raises a fundamental challenge to the traditional notion of accidental mutation. Here we address this finding with the replacement hypothesis, according to which pre-existing genetic interactions can lead directly and mechanistically to mutations that simplify and replace them. Thus, a gradual evolutionary process under selection can hone in on interactions of importance for the currently evolving adaptations, from which large-effect mutations follow that are relevant to these adaptations. We exemplify this hypothesis using multiple types of mutation, including gene fusion mutations, gene duplication mutations, A>G mutations in RNA-edited sites and transcription-associated mutations, and place it in the broader context of a system-level view of mutation origination called Interaction-based Evolution. Potential consequences include that similarity of mutation pressures may contribute to parallel evolution in genetically related species, that the evolution of genome organization may be driven by mutational mechanisms, that transposable element movements may also be explained by replacement, and that long-term directional mutational responses to specific environmental pressures are possible. Such responses need to be further tested by future studies in natural and artificial settings.

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Section: Mutational Replacement Of Rna Editingmentioning

confidence: 99%

Evolutionary Honing in and Mutational Replacement: How Long-Term Directed Mutational Responses to Specific Environmental Pressures Are Possible

Livnat¹,

Melamed²

2022

Preprint

View full text Add to dashboard Cite

show abstract

Evolutionary honing in and mutational replacement: how long-term directed mutational responses to specific environmental pressures are possible

Livnat

Melamed

2023

Theory Biosci.

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Recent results have shown that the human malaria-resistant hemoglobin S mutation originates de novo more frequently in the gene and in the population where it is of adaptive significance, namely, in the hemoglobin subunit beta gene compared to the nonresistant but otherwise identical 20A$$\rightarrow$$ → T mutation in the hemoglobin subunit delta gene, and in sub-Saharan Africans, who have been subject to intense malarial pressure for many generations, compared to northern Europeans, who have not. This finding raises a fundamental challenge to the traditional notion of accidental mutation. Here, we address this finding with the replacement hypothesis, according to which preexisting genetic interactions can lead directly and mechanistically to mutations that simplify and replace them. Thus, an evolutionary process under selection can gradually hone in on interactions of importance for the currently evolving adaptations, from which large-effect mutations follow that are relevant to these adaptations. We exemplify this hypothesis using multiple types of mutation, including gene fusion mutations, gene duplication mutations, A$$\rightarrow$$ → G mutations in RNA-edited sites and transcription-associated mutations, and place it in the broader context of a system-level view of mutation origination called interaction-based evolution. Potential consequences include that similarity of mutation pressures may contribute to parallel evolution in genetically related species, that the evolution of genome organization may be driven by mutational mechanisms, that transposable element movements may also be explained by replacement, and that long-term directed mutational responses to specific environmental pressures are possible. Such mutational phenomena need to be further tested by future studies in natural and artificial settings.

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Blood and saliva-derived exomes from healthy Caucasian subjects do not display overt evidence of somatic mosaicism

Hall

Mamrot

Frampton

et al. 2020

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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ADAR1 can drive Multiple Myeloma progression by acting both as an RNA editor of specific transcripts and as a DNA mutator of their cognate genes

Cited by 3 publications

References 61 publications

Evolutionary Honing in and Mutational Replacement: How Long-Term Directed Mutational Responses to Specific Environmental Pressures Are Possible

Evolutionary Honing in and Mutational Replacement: How Long-Term Directed Mutational Responses to Specific Environmental Pressures Are Possible

Evolutionary honing in and mutational replacement: how long-term directed mutational responses to specific environmental pressures are possible

Blood and saliva-derived exomes from healthy Caucasian subjects do not display overt evidence of somatic mosaicism

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