Human and bats genome robustness under COSMIC mutational signatures

Area of Science:

• Genomics
• Evolutionary Biology
• Cancer Research

Background:

• Carcinogenesis involves mutations fixing phenotypes in microenvironments.
• Cells exhibit robustness to mutational stressors to maintain fitness.

Purpose of the Study:

• To develop and apply a simulation pipeline for assessing gene and cellular robustness to mutagens.
• To investigate genome robustness against various mutational signatures, particularly APOBEC.

Main Methods:

• Developed Sinabro, a sequential mutation simulator for single base substitutions.
• Created a pipeline to measure gene and cell robustness under simulated mutagenesis.
• Analyzed over 70,000 sequences against 41 mutational signatures.

Main Results:

• Discovered significant human genome robustness to APOBEC mutational signature SBS2.
• Observed higher resilience to signatures causing C-to-T (G-to-A) mutations.
• Found GC content at the codon's wobble position influences robustness, favoring transition mutations.

Conclusions:

• APOBEC's role in aging and cancer is significant, with evolved countermeasures in the human genome.
• Long-lived bats exhibit greater APOBEC robustness than short-lived ones.
• Provides a baseline for human and bat genome robustness against aging and cancer-associated mutagens.