Plasticity in Neural Genomes During Early Life Experiences

What's the science?

The brain undergoes changes (i.e. plasticity) during early development, and these are thought to be due to gene-environment interactions. Retrotransposons are segments of DNA that are mobile and can essentially “jump” and insert themselves throughout the genome, and could be one way that DNA is modified by interactions with the environment. Currently, we don’t know whether retrotransposons play a role in changing DNA during early life. This week in Science, Bedrosian and colleagues observe the effects of early maternal care on retrotransposon levels in mouse DNA.

How did they do it?

Mice were divided into two groups: high and low maternal care (as evidenced by median natural levels of grooming and nursing over 2 weeks). They used droplet digital Polymerase Chain Reaction (ddPCR) to quantify the number of retrotransposons (‘L1’ retrotransposons, making up 17% of the mouse genome) in mice DNA from brain (hippocampus and frontal cortex) and heart tissue between the high and low care groups. They also manipulated the level of maternal care to test how this affected the number of retrotransposons over time.

What did they find?

There were more retrotransposons in the hippocampus in mice with low maternal care (but not in the heart or frontal cortex). When they manipulated the levels of maternal care by separating the mother and pup, retrotransposon levels also varied. They then tested what causes retrotransposon levels to change. They measured neurogenesis (the formation of new neurons) by staining hippocampal neurons, and found no differences (i.e. neurogenesis was not responsible for changes in retrotransposon levels). They also used bisulfite sequencing to measure the level of methylation of DNA (a DNA modification that affects gene expression). The retrotransposon regions in hippocampal DNA showed less methylation in mice with low maternal care (who have higher retrotransposon levels), suggesting that methylation is responsible for changes in retrotransposon levels with maternal care.

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What's the impact?

This is the first study to show that maternal care alters retrotransposon (i.e. jumping gene) activity in early life. Before, we did not understand exactly how early life experience can change the structure of DNA. Now we know that retrotransposons are one of the ways that DNA plasticity (i.e. changes) occurs in response to early life experiences.

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T. Bedrosian et al., Early life experience drives structural variation of neural genomes in mice. Science (2018). Access the original scientific publication here.