Quiescent cells also mutate

February 26, 2018, Pasteur Institute

For almost a hundred years, geneticists have believed that the more a cell divides the more mutations it acquires. However, research by scientists at the Institut Pasteur shows that quiescent cells, which do not divide, also acquire a particular type of mutation - deletions (mutations through loss of nucleobases).

Geneticists study heredity or the transmission of characters between generations. The genetic information responsible for these characters is contained in the DNA molecule, which is replicated each time a cell divides and transmitted to the daughter cells. "DNA replication machinery is powerful enough to faithfully transmit , and flexible enough to allow it to evolve through variations that we call mutations", explains Benoît Arcangioli, Head of the Dynamics of the Genome Unit at the Institut Pasteur.

What we currently know about mutations

Most mutations have a neutral effect, and positive or negative impacts on the characters of cells, individuals and species are rare. However, their build up, under the influence of natural selection, helps species to evolve.

In this context, and for close to one hundred years, geneticists have expressed mutations according to the number of cell divisions. "To keep it simple, the more a cell divides, the more mutations it acquires", explains Benoît Arcangioli. However, under natural conditions, cells spend relatively little time dividing and are often idle, or in the quiescent state, for example in adult organisms. The question therefore is whether mutations appear in these quiescent cells.

Quiescent cells also mutate

Benoît Arcangioli's team at the Institut Pasteur has shown that the DNA of quiescent cells also acquires mutations. "These mutations appear linearly over time and are different from those that appear during growth." During growth, mutations tends to increase the number of A/T (adenine/thymine) bases at the expense of C/G (cytosine/guanine) bases and insertions are more frequent than deletions. The situation is reversed in the quiescent state in the sense that changes between the A/T and G/C bases seem balanced and deletions prevail over insertions. As a consequence, "alternation between two mutating systems brings a dynamic balance to the composition and size of genomes in a given species". This also implies that quiescence, like growth, is subject to and will optimize the survival potential of cells when there is no division.

A role in male/female gamete dimorphism

"In many species, ranging from plants to humans, male gametes divide constantly while the opposite is observed for female gametes, adds Benoît Arcangioli. The main implication of our article is therefore that male and female gametes, each with their different mutations, will gradually impact their genetic material differently." The combination of two mutating methods could therefore play a key role in male and female gamete dimorphism.

Furthermore, by providing proof that these different mutation methods occur at different moments in cell life ( in the growth or quiescent state), the notion of time is introduced to the mutagenesis mechanism. "This concept of over time has two advantages, concludes the researcher. Firstly, it is consistent with the molecular clock theory used for evolution (and expressed in years) and, secondly, it gives an evolutionary force back to female gametes."

Explore further: Stem cell study may result in stronger muscles in old age

More information: Serge Gangloff et al, Quiescence unveils a novel mutational force in fission yeast, eLife (2017). DOI: 10.7554/eLife.27469

Related Stories

Stem cell study may result in stronger muscles in old age

February 26, 2018
Muscular function declines with age. A new study by researchers at Karolinska Institutet in Sweden shows how an unexpectedly high number of mutations in the stem cells of muscles impair cell regeneration. This discovery may ...

Focus on quiescent cells brings to light the essential role of RNA interference in transcription control

November 9, 2016
Some cells just don't get the respect they deserve. In fact, most cells don't. Over 99 percent of the innumerable cells on our planet exist in a state of quiescence. Pick up a handful of soil: it contains thousands of microorganisms, ...

Some mother cells kick DNA damage 'down the road' to offspring

May 17, 2017
A new University of Colorado Boulder study has shown that some dividing human cells are "kicking the can down the road," passing on low-level DNA damage to offspring, causing daughter cells to pause in a quiescent, or dormant, ...

Mutations in cancer often affect the X chromosome

October 18, 2013
Every case of cancer originates from changes in a person's genetic material (mutations). These usually occur as "somatic mutations" in individual cells during an individual's lifetime, rather than being inherited from a person's ...

Recommended for you

Why some human genes are more popular with researchers than others

September 18, 2018
Historical bias is a key reason why biomedical researchers continue to study the same 10 percent of all human genes while ignoring many genes known to play roles in disease, according to a study publishing September 18 in ...

Class of neurological disorders share 3-D genome folding pattern, study finds

September 18, 2018
In a class of roughly 30 neurological disorders that includes ALS, Huntington's Disease and Fragile X Syndrome, the relevant mutant gene features sections of repeating base pair sequences known as short tandem repeats, or ...

Researchers resolve decades-old mystery about the most commonly mutated gene in cancer

September 18, 2018
The most commonly mutated gene in cancer has tantalized scientists for decades about the message of its mutations. Although mutations can occur at more than 1,100 sites within the TP53 gene, they arise with greatest frequency ...

Study of one million people leads to world's biggest advance in blood pressure genetics

September 17, 2018
Over 500 new gene regions that influence people's blood pressure have been discovered in the largest global genetic study of blood pressure to date, led by Queen Mary University of London and Imperial College London.

Genetic mutations thwart scientific efforts to fully predict our future

September 17, 2018
Ever since the decoding of the human genome in 2003, genetic research has been focused heavily on understanding genes so that they could be read like tea leaves to predict an individual's future and, perhaps, help them stave ...

Gene therapy via skin protects mice from lethal cocaine doses

September 17, 2018
There are no approved medications to treat either cocaine addiction or overdose. Frequent users tend to become less and less sensitive to the drug, leading to stronger or more frequent doses. The typical result is addiction. ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.