Testing the Mother's Curse Hypothesis in Human Mitochondrial Genome Evolution.

Area of Science:

• Evolutionary biology
• Genetics
• Human health

Background:

• Mitochondrial DNA (mtDNA) is maternally inherited in vertebrates.
• Mutations harming only males can spread if they benefit females, leading to the mother's curse hypothesis (MCH).
• MCH predicts a higher mtDNA mutation load in males than females, with implications for health and evolution.

Purpose of the Study:

• To systematically test the mother's curse hypothesis in humans using extensive mtDNA variation.
• To investigate sex-specific differences in mtDNA mutation load and their impact on reproductive fitness and disease.

Main Methods:

• Analysis of genotypic and phenotypic data from ~0.5 million UK Biobank participants.
• Estimation of reproductive fitness (offspring number, sexual partners) for mtDNA variants in each sex.
• Examination of mtDNA variant frequencies and disease associations between sexes.

Main Results:

• No evidence found to support the mother's curse hypothesis in humans.
• A positive intersexual correlation in offspring number across mitochondrial haplogroups was observed.
• No significant sex-biased enrichment of male disease-associated mtDNA variants was detected.

Conclusions:

• The study provides no genomic support for the mother's curse hypothesis in humans.
• No detectable difference in mtDNA mutation load between males and females was found in the UK Biobank cohort.
• mtDNA variation does not appear to impose a greater mutational burden on males compared to females in humans.