Mutation bias, rather than binding preference, underlies the nucleosome-associated G+C% variation in eukaryotes

Area of Science:

• Molecular Biology
• Genomics
• Epigenetics

Background:

• The relationship between genetic content (G+C%) and epigenetic factors like nucleosome structure is complex.
• While nucleosome occupancy is known to correlate with G+C% in eukaryotic genomes, the causal relationship is debated.
• Existing theories suggest either nucleosomes preferentially bind G+C-rich DNA or G+C content is an evolutionary outcome of nucleosome occupancy.

Discussion:

• This study investigates whether nucleosome occupancy drives G+C% or if G+C% arises from nucleosome-induced mutations.
• In vitro reconstitution experiments used Saccharomyces cerevisiae (eukaryotic, nucleosome-shaped genome) and Escherichia coli (prokaryotic, no nucleosomes) DNA.
• The results challenge the prevailing view by indicating biased mutation, not biased occupancy, is the primary driver of G+C% variation associated with nucleosomes.

Key Insights:

• A strong positive correlation between nucleosome density and G+C% was observed for yeast DNA, mirroring in vivo findings.
• This correlation was largely absent in E. coli DNA, which is not shaped by nucleosome structure.
• The findings suggest that nucleosome occupancy leads to biased mutations, which in turn increase the G+C% of DNA over evolutionary time.

Outlook:

• This research reframes our understanding of genome evolution and the interplay between DNA sequence and epigenetic modifications.
• Further studies could explore the specific mutation mechanisms influenced by nucleosome structure across different organisms.
• Investigating the evolutionary consequences of nucleosome-mediated mutation bias can provide deeper insights into genome plasticity.