Germline selection shapes human mitochondrial DNA diversity

Area of Science:

• Genetics
• Human Evolution
• Population Genetics

Background:

• Mitochondrial DNA (mtDNA) constitutes a small fraction of the human genome but harbors genetic variation.
• Heteroplasmy, the presence of multiple mtDNA populations within an individual, is observed in a significant portion of the human population.

Purpose of the Study:

• To investigate the prevalence and transmission patterns of mitochondrial DNA heteroplasmy.
• To understand the selective forces acting on mtDNA variants during maternal inheritance.
• To explore the relationship between nuclear and mitochondrial genetic ancestry.

Main Methods:

• Analysis of 12,975 whole-genome sequences from 1526 mother-offspring pairs.
• Examination of mtDNA variant transmission across one generation.
• Validation of findings in a larger cohort of 40,325 individuals.

Main Results:

• 45.1% of individuals exhibit mtDNA heteroplasmy.
• Differential selection for and against mtDNA variants occurs across the genome.
• Newly arising heteroplasmies tend to align with nuclear genetic ancestry.

Conclusions:

• Human mtDNA populations are shaped by selection within the female germline.
• Nuclear genetic factors influence the transmission and consistency of mtDNA.
• This process ensures coordination between independent nuclear and mitochondrial genetic lineages.