In order to estimate whether a genetic disease can be inherited, you have to know how quickly the human genome mutates and how much it changes over generations. Researchers have now determined this change rate as precisely as never before and created the most comprehensive mutation atlas of the human DNA. Accordingly, parts of our genome change faster than others and much faster than before. However, the data has only come from a family. It is therefore still unclear whether every family has the same mutation speed, as the team reports in “Nature”.
Through environmental influences and random mutations, our genetic material changes in the course of life and from generation to generation. “The entire genetic variation that we see from individual to individual is the result of these mutations,” explains co-author Lynn Jorde from the University of Utah. These individual gene changes determine, for example, harmless appearances such as our eye color, but also health aspects – such as whether we can digest lactose or have a genetic disease.
It is estimated that the genes of every person differ from the genes of the two parents in hundreds of places. How often exactly new mutations occur and inherited in our genome has so far been unclear, since many of these changes occur in DNA regions that are particularly difficult to examine. These inheritance sections were “previously untouchable,” says co-author Aaron Quinlan from the University of Utah. So far, only about 60 to 70 individual, non-inherited mutations per generation have been proven.
Mutation rate of our genetic material on the test bench
Genetics around Lorde, Quinlan and Bostor author David Porubsky from the University of Washington have now combined several modern DNA analysis techniques in order to be able to completely examine the human genetic material and its change of change for the first time. The researchers sequenced the DNA of 28 relatives from four generations of the same family. The family living in Utah has been working with geneticists since the 1980s and has donated their DNA for research purposes. These rehearsals now analyzed Porubsky and his colleagues again, this time with five different technologies. Some of the methods recognize small gene mutations, others, especially big changes. The researchers then compared the parents’ genetic material with that of their children and each determined the mutation rate of their DNA.
It was confirmed that our genetic material is not a homogeneous mass, but mutated differently quickly depending on the section. Some regions therefore change faster than others. In total, Porubsky and his colleagues between 98 and 206 places in the genetic material where the DNA of a person differed from the parents and therefore only mutated after birth. On average, there were 152 individual, non-inherited gene changes.
Some parts of our DNA change even faster than previously assumed. “We have seen parts of our genome that are extremely changeable, almost every generation of a mutation,” says Quinlan. “The rate of de-Novo structure variants rose from 0.2 to 0.3 to three to four per generation compared to previous estimates,” writes the team. Other DNA segments, on the other hand, were more stable than expected and hardly changed over time. Based on the family genomes, the researchers have now created a kind of map of the human genome, which shows which sections quickly and which are rather slow.
Decision aid for parents
In the future, this card could help find the likely cause of genetic diseases. For example, if a disease-made genetic defect lies in a “mutation hotspot” of our genetic engineer, it is more likely to represent a new mutation that has only arisen in the course of a child’s life to inherit this mutation by a parent. In this case, the risk that the parents will get other children with the same disease is less. If, on the other hand, a child has a genetic change in a generally less variable part of our genetic engineer, it has probably inherited this mutation from the parents. Then the future children of these parents have a higher risk of also suffering from the genetic illness.
However, one question is still open to this application: “How generalizable are these results across families if you try to predict the risk of diseases or how genomes develop?” Explains Quinlan. In order to find out, Porubsky and his colleagues now want to examine the DNA from other people in follow -up studies and compare the genetic change rate of different families.
Source: David Porubsky (University of Washington) et al.; Nature, DOI: 10.1038/S41586-025-08922-2