Childhood impressions affect the genome
Lack of maternal care awakens "jumping DNA" in the genome
Kirill Stasevich, "Science and Life"
We often hear about how much influence childhood impressions have on us. And this influence may be even deeper than we imagine – as researchers from the Salk Institute have shown, the behavior of a mother affects the state of the genome in her children.
Initially, Tracy Bedrosian and her colleagues studied the relationship between stress and retrotransposon activity. Recall that transposons are called specific sequences in DNA that can copy themselves into new sections of the genome; they are therefore also called mobile genetic elements or "jumping DNA".
They have several varieties that differ in the molecular mechanisms of self–copying, and retrotransposons are one of such varieties. The transposon may not affect the well-being of the cell in any way if it copies itself into those DNA zones that do not encode anything. But if it invades the coding sequence, then the gene will most likely stop working as it should, and the cell may start major troubles.
It was assumed that the activity of transposons, their readiness to jump to new places, may depend on stress, and that maternal stress may thus affect the activity of the transposons of cubs while they are still in the womb. In experiments, pregnant mice were put in different cages, either very cramped and sparsely furnished, where it was unpleasant to live, or in spacious and with a bunch of toys, living in which was a pleasure. In mice, transposons – more precisely, one of them, the retrotransposon LINE-1 (L1) – really behaved differently, some had more copies of L1 in the genome, others less. But soon the researchers noticed that the activity of transposons depends not only on how much the mother mouse was nervous during pregnancy.
Further observations showed that one of the factors of the activity of mobile elements is how much attention the mother paid to newborn cubs. If the mouse often licked and cleaned the mice and generally ran around with them a lot, then they had fewer copies of transposons in the neurons of the hippocampus (one of the main memory centers) compared to those who were not taken care of so much.
Mouse hippocampal cells (their nuclei are colored blue) with an increased number of L1 gene proteins (green). Image: Salk Institute.
In other cells and organs – for example, in neurons of the frontal cortex and heart cells – there was no difference in transposons, that is, only the hippocampus felt the difference in care. Heredity had nothing to do with it: firstly, the parent mice also counted copies of the L1 transposon, and they had about equal numbers of these copies, and secondly, if the mice were passed to the foster mother, then everything still depended on how she took care of them.
Retrotransposons that copy themselves through the RNA stage: several RNA copies of a mobile element are synthesized on DNA, from which then, as from a template, DNA copies are "read" into other parts of the genome. That is, the activity of such a transposon depends on how open it is, how accessible it is to proteins that synthesize RNA. An article in Science (Early life experience drives structural variation of neural genomes in mice) states that there was a characteristic feature in the genome of mice that were little cared for: the part of DNA in front of the retrotransposon L1, which the proteins synthesizing RNA should bind to, was easily accessible to them.
Usually, cells try to turn off transposons using a special epigenetic mechanism for regulating genetic activity: DNA-methyltransferase enzymes hang methyl groups on DNA, and the same protein RNA synthesizing machines can no longer communicate with such a methylated fragment; as a result, the gene (whether it is a transposon or some other) falls asleep. But in mice deprived of affection, there was little methylating enzyme in the cells, epigenetic control weakened and the transposon woke up.
How exactly maternal care can affect the activity of epigenetic enzymes is still unclear, although the authors of the work believe that it's all about touching: the mother strokes and licks the cubs, and sensory signals from the skin somehow turn into molecular signals.
Another, no less curious question: does such an increased activity of transposons affect the mice themselves? How do their cognitive abilities develop (remember that transposons are active in the hippocampus – the memory center)? Does this affect their behavior? It is possible that it is partly thanks to transposons that negligent parents get children "with oddities"; however, before putting forward such strong hypotheses, we still need to wait for new experiments here.
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