Most m5C Modifications in Mammalian mRNAs are Nonadaptive

Area of Science:

• Molecular Biology
• Epigenetics
• Evolutionary Biology

Background:

• Messenger RNA (mRNA) 5-methylation (m5C) is a common internal RNA modification in eukaryotes.
• While m5C is known to influence some biological processes, its overall functionality in mRNA remains largely uncharacterized.
• Understanding the evolutionary conservation and adaptive significance of m5C is crucial for its biological interpretation.

Purpose of the Study:

• To investigate the genome-wide evolutionary characteristics of m5C modifications in human and mouse protein-coding genes.
• To determine whether most mRNA m5C modifications are functional and evolutionarily conserved.
• To assess the potential adaptive value of m5C modifications in mammalian mRNA.

Main Methods:

• Analysis of RNA sequencing data from 13 human and 13 mouse tissues.
• Genome-wide assessment of m5C modification occurrence, distribution, and evolutionary conservation across species.
• Estimation of the potential deleterious effects of observed m5C modifications.

Main Results:

• The occurrence of m5C modification on mRNA is exceedingly low across tissues and species.
• m5C modifications are largely unshared between humans and mice and lack significant evolutionary conservation.
• A substantial fraction of observed mRNA m5C modifications may be deleterious, suggesting a lack of adaptive function.

Conclusions:

• Most m5C modifications in mammalian mRNAs are likely nonadaptive.
• These findings challenge the presumed widespread biological significance of m5C and other mRNA modifications.
• Further research is needed to elucidate the specific roles, if any, of the few conserved or functional m5C sites.