Study Reveals Hidden Evolutionary Battle in Human Sperm

The contest for supremacy begins well before sperm embark on their final frantic race towards an egg.

Within the testicles, the struggle to pass on genes can begin even before sperm cells exist.

Mutations arising in the stem cells that generate sperm may give those cells an edge, enabling them to multiply in a survival-of-the-fittest contest with their unmutated neighbours.

There is, however, one catch: what is 'fittest' within the testicles is not necessarily good for any offspring the sperm may ultimately help produce.

A large-scale examination of mutations in human sperm has shown that this concealed evolutionary competition is much broader than researchers had appreciated.

Its effects may be substantial.

Many of the mutations discovered are linked with developmental disorders. As men get older, these mutations become more frequent in their sperm, increasing the likelihood that they could be inherited by their children.

Mutations in sperm-producing stem cells

Sperm production does not stop. Each day, an adult man's testes can produce between 150 and 275 million gametes.

This continuous production is driven by spermatogonial stem cells, located along the seminiferous tubules. They keep dividing, replenishing their own numbers while also creating cells that will eventually become sperm.

Yet every cell division carries a possibility of mutation caused by slightly imperfect DNA replication. Most such mutations will have no consequence, but occasionally one gives a new stem cell some form of advantage.

That mutated stem-cell line can then expand at the cost of neighbouring cells, spreading along the tubule and creating greater numbers of sperm that contain the mutation.

Researchers already knew that this process was possible. Earlier studies had found mutations in 13 genes that seemingly give sperm-producing stem cells this competitive advantage, and all are associated with severe developmental disorders.

However, the full scale of the effect was unclear. A team led by computational biologist Matthew Neville of the Wellcome Sanger Institute in the UK therefore set out to investigate it.

Using NanoSeq, an exceptionally accurate DNA-sequencing method, the researchers examined sperm samples from men aged 24 to 75.

They sought a particular signal: evidence that mutations were undergoing positive selection in the male germline. In other words, they were looking for mutations occurring more often than random chance would predict, indicating that they possessed a competitive advantage.

The findings were striking.

Their search identified more than 35,000 germline coding mutations. Of these, 40 genes displayed evidence of significant positive selection.

Thirty-one of those genes had not previously been connected with this unusual evolutionary competition. The remaining nine were among the 13 genes already identified.

Age increases the mutation load in sperm

Many of these findings have concerning implications for offspring who inherit the mutations. Of the 31 newly identified genes, 27 are associated with genetic disorders, and 16 are also established cancer genes.

These results are not merely theoretical. Mutations repeatedly observed in children with developmental disorders occurred 66 times more often in the sperm dataset than would be expected from the underlying mutation rate.

Age added a further dimension. Across the sperm genomes studied, mutations built up at a consistent rate of around 1.67 per year.

As men aged, the combined effects of that accumulation and positive selection for advantageous mutations drove the mutation burden substantially higher.

The team estimated that, at age 30, around 2 percent of a man's sperm contained a mutation likely to cause disease. At age 70, this proportion had increased to around 4.5 percent.

Their model projected far lower levels in the absence of positive selection: around 0.73 percent at age 30 and 1.6 percent at age 70.

What sperm mutations mean for offspring

This indicates that the evolutionary battle taking place inside the testes may raise the prevalence of potentially disease-causing mutations by roughly two- to threefold.

Importantly, this does not amount to a 4.5 percent chance of transmitting a genetic disorder to a child.

A mutation found in sperm must still pass several stages before it results in a living baby.

Some affected sperm may be less able to fertilise an egg, while other mutations may lead to an embryo that does not survive or to a pregnancy loss.

The researchers stress that the connection between mutations in sperm and the rate of disorders at birth is still uncertain.

Interestingly, evolution itself appears to impose a further filter.

When the researchers examined genetic variation in the broader human population, they found indications that many mutations favoured during sperm production are selected against over subsequent generations.

In effect, the testicles create the issue and the wider world clears up the aftermath.

That seems rather fitting.

The research was published in Nature in October 2025.

This article was fact-checked by Rachel Garner and edited by Peter Dockrill. Although we take pride in our process, we are only human. If you notice an error, please let us know.