How fast does the human genome change? Scientists have attempted to answer this question by studying mutation rates over several generations, and they found that some parts of the human genome tend to stay the same while others can mutate rapidly. This study, which took advantage of multiple types of genetic sequencing methods, has been reported in Nature.
"It's mutations that ultimately differentiate us from other species," noted study co-author Lynn Jorde, Ph.D., a professor of at the University of Utah."We're getting at a very basic property of what makes us human."
In this work, the researchers were able to use genetic data from a family that had volunteered for genetic studies, and contributed DNA from four generations. This is a fairly unusual situation that alllowed the investigators to compare parental DNA to offspring DNA over multiple generations. The DNA sequences were compared to determine what proportion of the genome was passed down, and how many times mutations had spontaneously arisen in children. These mutations, which are present in offspring but have not been passed down from parents, are known as de novo mutations.
The rate of mutation is something that we should know; it shows how quickly variation happens in our species, noted Jorde.
The genetic variations in our species that may lead to different eye colors or different disease or health states, are due to mutations, added Jorde.
It's been estimated that every person carries about 200 changes in their genome that were not passed down from either parent; this mutations arose spontaneously in the individual. Unfortunately, many of these changes occur in parts of the genome that are challenging to sequence. Previous work has tended to focus on mutations in regions of the genome that don't change that often. But the changeable regions might be highly repetitive, for example, which has presented obstacles to traditional sequencing methods. Cutting-edge techniques have now overcome many of these limitations.
This has revealed that some parts of human DNA change far more rapidly that we knew. There were many stable regions. But, "We saw parts of our genome that are crazy mutable, almost a mutation every generation," noted study co-author Aaron Quinlan, Ph.D., a professor and chair at the University of Utah.
Diseases that arise due to genetic changes in so-called mutation hotspots are more likely to be novel, and not inherited. This can inform genetic counseling, since a de novo mutation and its associated disease would be unlikely to occur in another child of those parents. But inherited genetic changes are far more likely to impact more than one child.
The researchers are planning to make the data from this study freely available so that other scientists can use it for further studies.
Sources: University of Utah Health Sciences, Nature
