Can affect your DNA

Early childhood experiences change DNA

Our genetic makeup could be less immutable than previously thought. This is because early childhood experiences not only influence the accumulation of DNA, they could even change the number of copies and the position of certain genes. US researchers have now discovered evidence of such environmental changes in the genetic code in mice. If these grew up neglected, certain “jumping genes” in the genome of their brain cells were more active: They made more copies of themselves and changed their position in the genome.

In early childhood and even in the womb, the decisive course for our health and our lives is set. Stress, environmental pollutants or malnutrition at this early age leave traces - also on our genetic make-up. Studies show that, for example, the mother's diet or mood influences certain deposits in the DNA of her unborn child. This so-called methylation, the presence of methyl groups (-CH3) on the genome, determines how easily the genes are accessible and thus has a decisive influence on gene activity. The DNA sequence, however, remains unchanged - at least that's what people thought up to now. "We're taught that our DNA is stable and immutable, but in reality it's much more dynamic," says senior author Fred Gage of the Salk Institute for Biological Studies in California.

The researcher explains: “There are genes in our cells that can copy themselves and move around in the genome.” These genes are the so-called Long Interspersed Nuclear Elements (LINE), also known as “jumping genes”. These DNA segments, which are typically around 6000 base pairs long, can copy themselves and then reuse them elsewhere in the genome. As a result, it can happen that, for example, cells in certain areas of the human brain differ from one another in terms of the number of their LINE copies. “Our DNA can very well change in a certain way,” says Gage. The most common of the previously known LINEs in mammals is LINE-1, it makes up around 17 percent of the human genome. So far, however, it was unclear which factors mobilize the “jumping genes” and whether this happens by chance or not.

Neglected mice and jumping genes

Gage and his colleagues may have found a possible answer through experiments with mice. For their study, they compared the DNA in the brains of mice children who either grew up with caring mothers or were neglected. In order to rule out hereditary effects, the researchers also used “adopted children” in some of the trials: They had the offspring of caring mothers raised by negligent mothers and vice versa. When the young animals were 21 days old, the scientists examined the LINE sequences in the hippocampus of their brain - this region is known for the fact that the jumping genes are particularly active here.

The result: The mice that had been neglected from birth had a noticeably high number of LINE-1 copies in the genome of their hippocampus cells - significantly more than their conspecifics with caring mothers. This applied both to the mice raised by their own mothers and to the “adopted children. "It has been speculated for a long time that the changes to the LINEs will not happen by chance," says Gage. “Our results now suggest that this plasticity at the level of the DNA sequence could occur in response to environmental factors.” In the case of the child mice, the increased stress from neglect could have caused the increased activity of the jumping genes, the researchers speculate. If this is confirmed, then this would be the first evidence of a DNA change due to external influences.

DNA accumulations as a trigger?

The scientists have also found initial indications of how early childhood stress manages to influence the genetic code. When they examined the genetic makeup of the mouse children more closely, they also found differences in the methylation of the DNA. The mouse pups that had been neglected had fewer genetic attachments than the animals with caring mothers. The researchers suspect that the amount of attachments influences the behavior and mobility of jumping genes: the fewer attachments there are in the gene areas with LINE-1 elements, the easier it is for them to copy and move. "Differences in methylation and expression could therefore be one of the mechanisms that lead to the changes in the copy number of the LINE-1 elements," they write.

It is still unclear whether and what consequences such changes in the number of jumping genes will have. Theoretically, however, it would be possible that newly inserted extra copies influence the activity and reading of neighboring genes, as the researchers explain. It must also be clarified to what extent these results can be transferred to humans. It is already known that early childhood experiences can also permanently change the pattern of attachments to the genome in us. However, our LINE sequences are less numerous and mobile than those of the mice. Whether the changes in our jumping genes will still occur remains to be investigated.

Tracy Bedrosian (Salk Institute for Biological Studies, La Jolla) et al., Science, doi: 10.1126 / science.aah3378

23 March 2018

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