Mitochondrial DNA mutations in human oocytes undergo frequency-dependent selection but do not increase with age

Area of Science:

• Genetics
• Cell Biology
• Reproductive Biology

Background:

• Mitochondria are crucial organelles providing cellular energy.
• Mitochondrial DNA (mtDNA) is maternally inherited and prone to mutations.
• Age-related mtDNA mutations are linked to diseases, but their status in human oocytes is unclear.

Purpose of the Study:

• To investigate the accumulation of de novo mtDNA mutations in human oocytes with age.
• To compare mutation patterns in oocytes with somatic tissues (blood and saliva).
• To understand the mechanisms protecting oocyte mtDNA from age-related mutations.

Main Methods:

• Employed highly accurate duplex sequencing to analyze full-length mtDNA from single human oocytes, blood, and saliva samples.
• Studied women aged 20-42 years.
• Analyzed mutation frequencies and distribution in coding and non-coding mtDNA regions.

Main Results:

• Detected de novo mtDNA mutations in all analyzed tissues.
• Observed a significant age-related increase in mtDNA mutations in blood and saliva, but not in oocytes.
• Found evidence of frequency-dependent purifying selection acting on mtDNA mutations in oocytes.
• Identified selection favoring amino acid changes in protein-coding regions of somatic mtDNA.

Conclusions:

• Human oocyte mtDNA is remarkably protected against the accumulation of mutations with aging.
• Mitochondrial DNA in oocytes exhibits distinct selective pressures compared to somatic tissues.
• These findings have implications for understanding age-related diseases and reproductive health in an aging population.