Methylation-associated mutagenesis underlies variation in the mutation spectrum across eukaryotes

Area of Science:

• Genomics
• Evolutionary Biology
• Molecular Biology

Background:

• Mutation spectra differ across species and environments.
• Previous research primarily focused on trinucleotide mutation types in mammals.
• A broader survey of mutation variation across eukaryotes is needed.

Purpose of the Study:

• To characterize pentanucleotide (5-mer) noncoding mutation spectra across 108 eukaryotic species.
• To identify key drivers of variation in mutation spectra.
• To investigate the relationship between CpG mutation rates, genomic CpG depletion, and methylation levels.

Main Methods:

• Whole-genome resequencing data from 108 eukaryotic species.
• Bayesian analysis to characterize pentanucleotide mutation spectra.
• Analysis of transition/transversion ratios and CpG site mutability.

Main Results:

• Cytosine transition mutability at CpG sites is a primary driver of eukaryotic mutation spectra variation.
• Other sources of variation in the transition/transversion ratio also contribute significantly.
• Inferred CpG mutation rates strongly predict genomic CpG depletion.
• CpG mutation rates are not predicted by average genome-wide CpG methylation levels.

Conclusions:

• Mutagenesis plays a crucial role in shaping eukaryotic genome composition.
• CpG site dynamics are central to understanding mutation spectra.
• Further research is needed to elucidate the mechanisms governing mutation rates across eukaryotes.