A new study by scientists at Rockefeller University published in the journal Nature Ecology & Evolution has shed light on why older men pass on more mutations to their offspring than younger men do.
The study found that mutations are common in the testes of both young and old fruit flies, but more abundant in older flies. Additionally, many of these mutations seem to be removed in younger fruit flies during spermatogenesis by the body’s genomic repair mechanisms, but they fail to be fixed in the testes of older flies.
The researchers in Li Zhao’s lab studied mutations that occur during the production of sperm from germline cells, known as spermatogenesis. They found that at every stage of spermatogenesis, there are more mutations per RNA molecule in older flies than in younger flies. This suggests that both the older germline being less efficient at mutation repair and the older germline starting out more mutated contribute to this phenomenon.
Previous research has suggested that a faulty transcription-coupled repair mechanism, which only fixes transcribed genes, could be to blame for this increased mutation rate in older sperm. The researchers plan to expand their analysis to more age groups of flies and test whether or not this transcription repair mechanism can occur, and if so, identify the pathways responsible for the difference between old and young flies in terms of mutation repair.
The study has important implications for human health and evolution, as investigating the mutation patterns in fruit flies can offer new insights into the effect of new mutations in humans. The findings also highlight the importance of understanding the mechanisms that underlie inherited-disease risk in humans, as older men are more likely to pass on mutations that can lead to inherited diseases.