Replication competition drives the selective mtDNA inheritance in Drosophila ovary

Area of Science:

• Genetics
• Molecular Biology
• Developmental Biology

Background:

• Purifying selection against harmful mitochondrial DNA (mtDNA) mutations is known in humans and animals.
• The exact mechanism of this selection process remains unclear.

Purpose of the Study:

• To develop a novel in situ imaging technique for visualizing and quantifying mtDNA variants at single-molecule resolution.
• To elucidate the mechanism of purifying selection acting on mtDNA during early development.

Main Methods:

• Development of a highly specific in situ imaging method for Drosophila ovaries.
• Visualization of mtDNA variants differing by few nucleotides at single-molecule resolution.
• Analysis of mtDNA variant dynamics during specific developmental windows.

Main Results:

• Selection against deleterious mtDNA variants occurs during germline cyst differentiation.
• The proportion of harmful mtDNA variants decreases without a change in absolute copy number.
• Healthier mtDNA variants outcompete deleterious ones through more frequent replication.

Conclusions:

• Mitochondrial genome transmission is governed by replication competition, not active elimination.
• This study provides direct evidence for a fundamental mechanism of mtDNA selection.
• The findings offer insights into the maintenance of mitochondrial genome integrity.