Molecular mechanisms of change in identical twins

3 minute read

I'm fairly unique; not only do I study genetics, but I also have a pair of identical twins. So I notice their differences, both in how they look and how they act. From a genetic standpoint, these differences are neither unusual nor unexpected: most traits are influenced strongly by the environment, even if they are also influenced by heredity. My twins haven't had exactly the same environment -- nobody has. So they are different, for reasons stemming from their different positions in utero, their slightly different diets, their different histories of illness, and so on.

But just saying that "the environment done it" doesn't really enlighten as to the mechanism underlying these differences. How does the environment alter the phenotype? Identical twins are not interesting merely because they are different: everybody's different. Instead, they are interesting because they show how the same genome can unfold differently with slightly different conditions.

This week, a group of Spanish researchers led by Mario Fraga of the Spanish National Cancer Center have examined some of the molecular processes by which the environment can register alterations in gene expression, thereby influencing the phenotype.

In a description of the research, Rick Weiss of the Washington Post writes:

The new research, led by Mario F. Fraga and Manel Esteller of the Spanish National Cancer Center in Madrid, focused on two biological mechanisms that influence gene activity. In one, called DNA methylation, enzymes inside a cell attach a minuscule molecular decoration to a gene, deactivating that gene. In the other, called histone acetylation, a dormant gene is made active again.
These altered genetic settings can last a lifetime (though they are not passed down to a person's offspring) and can be important if, say, the gene turned off is one that protects against cancer. The extent to which epigenetic changes are preprogrammed from birth or spurred by factors outside the body has been unclear.
In the new work, described in today's issue of Proceedings of the National Academy of Sciences, researchers measured the extent to which twins of various ages, from 3 to 74, differed in the number and variety of genes that had been either turned on or shut down by epigenetic processes. They found that young twins had almost identical epigenetic profiles but that with age their profiles became more and more divergent.

This is not merely the phenotype being partially determined by the environment; it is a trace of one of the mechanisms of that influence. What happens to you can result in your genes being turned on or off -- sometimes for a lifetime. These shifts are not mutations, but controls that cause alterations of gene expression.

And the shifts arise -- at least some of the time -- because of environmental events:

In a finding that scientists said was particularly groundbreaking, the epigenetic profiles of twins who had been raised apart or had especially different life experiences -- including nutritional habits, history of illness, physical activity, and use of tobacco, alcohol and drugs -- differed more than those who had lived together longer or shared similar environments and experiences.

So far, the articles I've seen have focused on the "epigenetic" aspect. It is just a fancy way of saying that the expression of genes can be altered -- they can be turned on or off -- by events that affect the cell. The cumulation of such small effects across the body as a whole can lead to relatively big changes. Here, people have focused on the increase in cancer or other disease risk that can result from certain epigenetic changes. But more broadly, these changes are ways that conditional adaptations to different environments are implemented. If it is sometimes advantageous to produce a given protein, and sometimes better not to produce it; then a process that could control the production in light of circumstances would be very useful. Methylation and acetylation are two such processes.

For me, I will now know what to tell my twins when they ask why they're different even if they're identical. You're methylated, and she's acetylated. Hmmm... "Methyl" and "Acetyl" would be quite the twin names...