Although mutations — the fundamental process by which genomic variation is acquired — are necessary to the evolution and success of a species, they are also the origin of all genetic disease. Hence, defining the mechanisms that control their occurrence is crucial to our basic understanding of genome biology, disease mechanisms and, ultimately, evolution.
Anne Goriely and her colleagues at the University of Oxford previously described a process that they termed ‘selfish selection,’ which promotes harmful mutations in the testes of all men as they age1. These mutations hijack the way sperm is produced by providing a selective advantage to the testicular cells in which they occur (which is why they are called ‘selfish’) in a manner similar to that of tumor growth. Goriely and her team showed that these selfish mutations can occasionally be associated with testicular tumors2. These mutations accumulate progressively in the sperm of aging men, leading to an increased risk of being passed on to the next generation in older fathers. So far, this mechanism has been demonstrated only in rare conditions associated with severe malformations or lethality in the newborn child1. However, these may represent only the most obvious and extreme cases of a basic process that is more common than we realize.
Many genes that control cell decisions in the testes are also re-expressed later in different organs, including the brain, where they play essential roles in brain development and functioning. Goriely and her group propose that the process of ‘selfish spermatogonial selection’ taking place in the testes contributes to the genetics of other diseases, including autism, and is important for the evolution of our genome3.
The researchers aim to exploit recent advances in DNA technologies to explore the relationship between the process of selfish spermatogonial selection and the occurrence of specific mutations that have been associated with neurocognitive disorders, by looking for these mutations directly within the testes of aging men.