Nature: Mutant sperm precursor cells multiply at the expense of healthy cells

Scientists have found evidence of a real “battle for survival” inside the male testes: mutant precursor cells that give rise to sperm can multiply at the expense of healthy cells, and the proportion of potentially harmful mutations increases with age. The study was published in the journal Nature.

Researchers from the Wellcome Sanger Institute analyzed more than 35,000 mutations and identified 40 genes that give cells a reproductive advantage, 31 of which had not previously been identified. Of concern, 27 of the newly identified genes are associated with inherited disorders, while 16 are linked to cancer. Mutations previously observed in children with developmental disorders were found in sperm 66 times more often than would be expected by chance.

The process is known as positive selection: some mutations cause cells to divide more actively, allowing them to gradually outcompete normal cells. As a result, the proportion of sperm carrying disease-causing mutations roughly doubles with age, from around 2% at age 30 to as much as 4.5% by age 70. Positive selection itself increases the prevalence of harmful mutations by another two- to threefold compared with what would be expected from the simple accumulation of genetic errors.

This helps explain why the risk of certain genetic disorders in children increases with paternal age. However, the authors emphasize that the presence of a mutation in a sperm cell does not necessarily mean that a child will develop a disease. Natural biological “filters” and selection at later stages also come into play. Nevertheless, the study provides a detailed demonstration that male germ cells are an arena of ongoing evolutionary competition.

Paternal age has long been associated with a modestly increased risk of autism, schizophrenia, and a number of rare syndromes in children, with the accumulation of mutations in sperm considered a major contributing factor. The new study shows that the process involves not only the accumulation of genetic errors but also their active selection.

The findings are not necessarily a cause for concern but rather provide insight into the underlying biology: the absolute risks for an individual family remain small.

It should be noted that the study was originally published in 2025.

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