Why older fathers inherit more mutations

The researchers examined mutations that occur in male fruit flies during the production of sperm. Mutations were common in the testicles of young and old fruit flies, but more common in older flies. Many of these mutations were repaired during sperm production in the young flies, but hardly at all in the testicles of older flies.

“We tried to test whether the older flies’ sperm production is less efficient at repairing mutations, or whether it simply starts out more mutated,” said bioinformatician Evan Witt. “Our results show that it is actually both. At every stage of sperm production, older flies have more mutations per RNA molecule than younger flies.”

The genome keeps itself in order with various self-repair mechanisms. These must work particularly efficiently in the testicles, because that is where the genes are particularly active. With older flies, this no longer works as reliably.

For their study, the research team examined and compared the genome of individual cells from the body and the sperm-forming cells of the flies: mutations that only occur in the sperm-producing cells but not in other body cells must have arisen there. Further comparisons of the genomes of parents and offspring provided clues as to whether a mutation was inherited. For their experiments, the researchers analyzed the genetic material from the testicles of around 300 fruit flies, regarding half of which were young (48 hours old) and the other half old (25 days old).

Which: DOI 10.1038/s41559-022-01958-x

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