Self-DNA Exposure Induces Developmental Defects and Germline DNA Damage Response in Caenorhabditis elegans

Area of Science:

• Innate immunity and molecular biology
• Genetics and developmental biology

Background:

• Organisms possess innate immune systems to detect foreign nucleic acids (pathogen-associated molecular patterns) and self-molecules indicating damage (damage-associated molecular patterns).
• Mis-localized self-DNA can trigger detrimental responses, but its effects when delivered through diet remain largely unexplored.

Purpose of the Study:

• To investigate the impact of dietary self-DNA on the nematode Caenorhabditis elegans.
• To explore the molecular pathways involved in self-DNA sensing and response.

Main Methods:

• Feeding C. elegans with Escherichia coli genomic libraries, including self (C. elegans) and non-self (Medicago truncatula) DNA.
• Observing effects on embryogenesis, larval development, and gametogenesis.
• Analyzing DNA damage and apoptosis in gonadal germ cells.

Main Results:

• A diet enriched with self-DNA significantly impaired embryogenesis, larval development, and gametogenesis in C. elegans.
• Dietary self-DNA induced DNA damage and activated p53/CEP-1-dependent apoptosis specifically in gonadal germ cells.
• These adverse effects were specific to the self-DNA diet.

Conclusions:

• Dietary self-DNA poses a significant threat to reproductive fitness and development in C. elegans.
• The study identifies key molecular pathways, including DNA damage response and apoptosis, involved in sensing dietary self-DNA.
• Findings suggest potential applications for dietary self-DNA in biological pest control strategies.