Global and local genomic features together modulate the spontaneous single nucleotide mutation rate

Area of Science:

• Genomics
• Evolutionary Biology
• Molecular Biology

Background:

• Spontaneous mutations, particularly single nucleotide mutations (SNM), are fundamental to evolution, driving speciation and adaptation.
• Understanding the genomic factors influencing SNM rates is crucial for deciphering evolutionary processes across diverse life forms.

Purpose of the Study:

• To conduct a meta-analysis quantifying the impact of global and local genomic parameters on spontaneous SNM rates.
• To investigate these influences across prokaryotes, unicellular eukaryotes, and multicellular eukaryotes.

Main Methods:

• Meta-analysis of wild-type sequence data from diverse taxa.
• Evaluation of global genomic features (genome size, GC content, repeat fraction, gene count, strand bias) and local genomic features (local GC, repeat, CpG content, CpG islands).
• Comparison of linear and non-linear models for predicting SNM rates.

Main Results:

• Spontaneous SNM rates correlate with numerous genomic features in prokaryotes and unicellular eukaryotes.
• In multicellular eukaryotes, only the number of coding genes showed a correlation, primarily from vertebrate data.
• Local GC and CpG content are significant in unicellular eukaryotes; local repeat fraction is important in prokaryotes and some eukaryotes.
• Non-linear models generally provided a better fit for predicting SNM rates based on these features.
• Prokaryotic strand asymmetry influences SNM rates, but the SNM spectrum does not.

Conclusions:

• Genomic features significantly modulate spontaneous SNM rates across different domains of life, with varying importance.
• The predictive relationships between genomic features and SNM rates are often non-linear.
• These findings provide insights into the evolutionary forces shaping genome stability and diversity.