Human and bats genome robustness under COSMIC mutational signatures DOI Creative Commons
Joon-Hyun Song, Ying Zeng, Liliana M. Dávalos

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 7, 2024

Carcinogenesis is an evolutionary process, and mutations can fix the selected phenotypes in selective microenvironments. Both normal neoplastic cells are robust to mutational stressors microenvironment extent that secure their fitness. To test robustness of genes under a range mutagens, we developed sequential mutation simulator, Sinabro, simulate single base substitution given process. Then, pipeline measure those mutagenesis processes. We discovered significant human genome APOBEC signature SBS2, which associated with viral defense mechanisms implicated cancer. Robustness evaluations across over 70,000 sequences against 41 signatures showed higher resilience predominantly causing C-to-T (G-to-A) mutations. Principal component analysis indicates GC content at codon's wobble position significantly influences robustness, increased noted transition compared transversions. tested our results bats extremes lifespan-to-mass relationship found long-lived bat more than short-lived one. By revealing ranked highest (and much number APOBEC) genome, this work bolsters key potential role APOBECs aging cancer, as well evolved countermeasures innate mutagenic It also provides baseline processes

Language: Английский

Human and bats genome robustness under COSMIC mutational signatures DOI Creative Commons
Joon-Hyun Song, Ying Zeng, Liliana M. Dávalos

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 7, 2024

Carcinogenesis is an evolutionary process, and mutations can fix the selected phenotypes in selective microenvironments. Both normal neoplastic cells are robust to mutational stressors microenvironment extent that secure their fitness. To test robustness of genes under a range mutagens, we developed sequential mutation simulator, Sinabro, simulate single base substitution given process. Then, pipeline measure those mutagenesis processes. We discovered significant human genome APOBEC signature SBS2, which associated with viral defense mechanisms implicated cancer. Robustness evaluations across over 70,000 sequences against 41 signatures showed higher resilience predominantly causing C-to-T (G-to-A) mutations. Principal component analysis indicates GC content at codon's wobble position significantly influences robustness, increased noted transition compared transversions. tested our results bats extremes lifespan-to-mass relationship found long-lived bat more than short-lived one. By revealing ranked highest (and much number APOBEC) genome, this work bolsters key potential role APOBECs aging cancer, as well evolved countermeasures innate mutagenic It also provides baseline processes

Language: Английский

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