The fertilization of an egg gives rise to a genetically unique cell lineage that unfolds as cell division ensues - eventually to produce a mature organism that in the case of humans comprises some 100 million, million cells. Meanwhile, over the lifetime of the organism, cellular DNA accumulates mutations that are not inherited from parental DNA - these so-called "somatic" mutations carry a record of the lifetime experiences of each cell.
Now scientists in the UK have found a way to reconstruct the genetic life history of individual cells back to their origins in the fertilized egg. They report their findings in the journal Nature.
The achievement could help us better understand diseases like cancer, as senior author Mike Stratton, professor and director of the Wellcome Trust Sanger Institute in Cambridge explains:
"...by looking at the numbers and types of mutation in each cell we will be able to obtain a diary, writ in DNA, of what each healthy cell has experienced during its lifetime, and then explore how this changes in the range of human diseases."
The team sequenced DNA of cells from different types of tissue
In their paper, Prof. Stratton and colleagues explain how they developed the approach by looking at cells from the stomach, large and small bowel, and prostate of mice.
They cultured the single cells to produce enough DNA to carry out sufficiently accurate genome sequencing.
When they compared cell DNA from one type of tissue to that of another, they found differences in the numbers of mutations the different cells had accumulated - which they suggest is probably because of the differences in rates of cell division.
Each time a cell divides, its DNA accumulates small changes. Think of transcribing a page of writing - there is a small chance that a couple of typos or accidental changes creep in. Now think of millions of pages, and transcribing them all again and again.
Patterns - as well as rates - of mutation varied among the cell types
But the team found it was not only the numbers of mutations that were different among the different cell types, but also the patterns. They say this suggests the cells have been exposed to different types of DNA damage and repair, reflecting their different lifetime experiences.
As not only the numbers of mutations were different among the different cell types, but also the patterns, the team suggests the cells have been exposed to different types of DNA damage and repair.
Back to the document analogy - the body attempts to put right any copying errors that creep in with DNA repair processes - rather like proofreaders checking over typescripts.
So, by looking at the numbers and types of mutations in a cell's DNA, the team could work out if it had divided only a few or many times - and also detect the imprints or "signatures" of DNA damage that the cell had undergone over the life of the organism.
The other thing they did was compare mutation pattern and rates among the different cell types, which helped them map a detailed tree of development from the fertilized egg.
The authors point out that they were working with healthy mice, but if the mutation rates are similar in humans, then it may well be possible to use their methods to study the life histories of human cells.
First author Dr. Sam Behjati, also of the Sanger Institute, says:
"If we can better understand how normal, healthy cells mutate as they divide over a person's lifetime, we will gain a fundamental insight into what can be considered normal and how this differs from what we see in cancer cells."
Meanwhile, Medical News Today recently reported how researchers are paving the way for virus-like DNA nanodevices to diagnose disease and make drugs. One of the barriers to using "smart DNA nanorobots" to diagnose diseases like cancer or target drugs directly to chosen tumors, or even manufacture them on the spot, has been how to get them to evade the immune system. In this new study, a team from Harvard's Wyss Institute for Biologically Inspired Engineering in Boston, MA, shows how.
Written by Catharine Paddock PhD