Clustered mutations in hominid genome evolution are consistent with APOBEC3G enzymatic activity

Area of Science:

• Genomics
• Evolutionary Biology
• Molecular Biology

Background:

• Mutation accumulation drives organismal divergence and evolution.
• The AID/APOBEC enzyme family induces somatic mutations in cancer via cytosine deamination.
• APOBEC3 genes expanded rapidly in primates.

Purpose of the Study:

• To investigate if APOBEC3 enzymes generate unique germline mutation clusters contributing to primate evolution.
• To screen for APOBEC3-induced mutagenesis patterns across hominids.

Main Methods:

• Comparative genomic analysis of hominid genomes.
• Screening for mutation clusters with APOBEC3G mutagenesis signatures.

Main Results:

• Thousands of mutation clusters were detected across primate evolution.
• These clusters exhibit characteristics consistent with APOBEC3G activity.
• The mechanism shows a preference for transcribed and regulatory regions.
• It generates clusters of point mutations within a single generation.

Conclusions:

• APOBEC3G-induced mutations have significantly contributed to the evolution of hominid genomes.
• This represents the first evidence of site-directed, enzyme-induced genome evolution.
• The exaptation of an antiviral mechanism provides a novel source of genomic variation in hominids with functional implications.