Human semen does not it only accumulates genetic mutations with age; as the percentage of sperm carrying potentially grave mutations increases, the risk of disease development in offspring increases.
This is according to a fresh study conducted by scientists from the Sanger Institute and King’s College London. The team sequenced semen samples from people aged 24 to 75 using high-precision technologies and found that the male germline (the line of sperm-producing cells) is subject to a combination of mutations and positive selection.
The researchers used a duplex sequencing technique called NanoSeq, which can detect occasional mutations with a very low margin of error. This enabled them to analyze 81 semen samples from 57 donors. The results showed that an average of 1.67 fresh mutations appear in male sperm each year.
However, the most striking aspect of the study is not narrow to the elementary accumulation of mutations with age. The authors found that the male germline is under positive selection. This means that certain mutations give an advantage to the cells that produce sperm and reproduce. They determined that many of these mutations occur in genes associated with developmental disorders or a predisposition to childhood cancer.
“We expected to find evidence that selection influences mutations in sperm,” said Matthew Neville, co-author of the published study this month in the journal Nature. “We were surprised by how much the number of mutations in sperm that cause serious diseases is increasing.”
What does this mean for children of older fathers?
Scientists have estimated that about 3 to 5 percent of sperm from middle-aged and older men have a potentially pathogenic mutation in the exome (the coding part of the genome). This represents a higher risk than previous estimates. More specifically, the estimated percentage for men in their 30s was close to 2 percent, while for men in their 70s it was around 4.5 percent.
From an evolutionary and clinical perspective, the implications are significant. Evolutionary shows that the male germline is not simply a “machine” that accumulates errors: there is a energetic process of mutation and selection that can modify the genetic “quality” of sperm as the father ages.
However, on the clinical side, it raises questions about reproductive planning, genetic counseling, and the additional risks associated with an older father. The authors argue that while the percentages remain modest, accumulation is not only linear, but also has an element of selection that favors mutations with the potential to spread.