May 20, 2013 | 7
Have you ever known a pair of identical twins? Not just the ones that look alike, but identical twins that really were part of, at some point, the same egg and sperm combination, that then split early in development to create two “identical” people, with the same genetics.
If genetics really were the be all and end all of our behavior, you might expect these identical twins to look the same, act the same, speak the same, move the same. They have the same DNA, they should essentially, be the same people.
But they’re not.
I have known several pairs of identical twins. Yeah, the resemblance is more than a bit uncanny, but without a doubt, they are not the same people. They have different interests, different behaviors. One is more outgoing, while one is more reserved. One may be into art while the other is into engineering.
You might then think that the environment had something to do with it. After all, often twins are exposed to different things. There are famous twin studies of identical twins exposed to different situations (often reared separately), which help to understand the interactions between genetics and environment.
But then, most identical twins are reared together, not separately. They go to the same school, know most of the same people, often share the same room. Their environments do not differ all that much. In theory, in terms of environmental influence, many identical twins should have the same exposure.
And they do. But it’s not just the environment that matters, or just the genetics that matter. It’s how you use them.
Freund et al. “Emergence of individuality in genetically identical mice” Science, 2013.
The differences between identical twins aren’t limited to humans. As a good example, many scientists who work in animal behavior work with genetically identical mice. And they are VERY identical, inbred over many generations to make one mouse pretty much the same as another. This helps to decrease variability of behaviors and biology, so that when we are looking for differences (say, a response to a drug or treatment), we can better separate them from the noise.
But while these mice are genetically identical…they aren’t behaviorally. Yes, the variability is reduced, but one mouse will usually be more anxious than another, or more active than another, or smarter than another, or fatter than another, even within the same strain. We can get identical genetics, but the behavior and physiological result is never perfect, the mice remain individuals.
And the question becomes: what produces this individuality?
To examine this, Freund et al took a large group of genetically identical female mice (C57 Black mice, the mouse of choice for many studies, in this case the kind from the Charles River supplier, which is something that really can make a difference). Half were used as controls, in control cages with cage mates, and normal food and water available. The other half received a higher enriched environment. While sometimes “enriched” can mean a larger cage with some tubes and chew toys, in this case, the enriched environment was a mouse paradise, with multiple levels, loads of tubes, different water spouts, nesting boxes, the whole nine yards.
(Figure 1 from Freund et al, 2013)
The enriched mice were also equipped with tags so that their activities could be tracked.
Then, the controls were left, and the enriched mice were left, for 12 weeks. That’s a significant portion of a mousey lifetime.
At the end, the mice were examined for changes in hippocampal neurogenesis. Hippocampal neurogenesis, the birth of new neurons in the hippocampus, occurs throughout adult life, but can be affected by environmental stimuli or drug treatment. Long term antidepressant treatment, for example, can increase hippocampal neurogenesis, while stress can decrease it. Hippocampal neurogenesis can also be increased in response to things like new environments that animals have to learn about. And it is increased in response to things like an enrichment.
So it was no surprise that, in the mice exposed long term to the awesome mouse paradise, hippocampal neurogenesis was increased. But it wasn’t increased to the same degree in all the mice. There were individual differences. And the authors of this study took the opportunity to try and examine WHY those differences in neurogenesis might be occurring.
They used the RFID tags on the enriched mice to track where they had gone during the course of the experiment (3 months of data!). And they found that, while some mice stayed close to “home” in limited territories, others ranged all over the place.
(Figure 2B, 2C, Freund et al, 2013)
You can see on the left the more limited range of a more “cautious” mouse. This mouse had low roaming entropy, it liked its small range and didn’t need to venture out of it. On the right, however, you can see a high roaming entropy mouse. This one ranged all over. And on the bottom graph, you can see that these actions diverged over time, a subset of the enriched mice stuck to their limited range, while the other subset roamed widely.
And this roaming CORRELATED with the amount of hippocampal neurogenesis. Mice that had limited roaming had lower hippocampal neurogenesis than mice that had higher roaming. This shows a solid set of individual differences, in genetically identical mice, exposed to exactly the same environment. It wasn’t the genetics, it wasn’t the environment, instead, it was how the animals experienced the environment they were in.
What’s causing this different environmental experience? The authors put forth several hypotheses. One of them is epigenetics, the modifications made to the “outside” of the genome that determine how it is transcribed, and which can produce differences in gene expression. There are also options like intrauterine position (as mice have litters of pups, often up to 10-14 at a time, the position in the uterus, whether you’re between two boys or a boy and a girl or two girls, for example, could expose you to different hormone levels during development which could then affect behavior (probably through altering epigenetics). And of course there is the distinct possibility of random genetic mutation.
All of these are possible. But it will be interesting to see where the group goes with this work, and how they decide to look at these new, individual mice. Because the enriched environment showed that genetically identical mice, in an identical environment, can become individuals. Like twins, it’s not just the environment, or the genetics, but the combination, and how you experience it.
Freund, J., Brandmaier, A., Lewejohann, L., Kirste, I., Kritzler, M., Kruger, A., Sachser, N., Lindenberger, U., & Kempermann, G. (2013). Emergence of Individuality in Genetically Identical Mice Science, 340 (6133), 756-759 DOI: 10.1126/science.1235294