Chromosomes from 3-year-old twins (left) are virtually identical. But those from 50-year-old twins (right) show changes in gene expression in red and green.© PNAS

Identical twins may have less in common than they think. A study now shows that the expression of their genes gets more and more different with age.

The findings could help to explain why one twin may develop a genetically influenced disease, such as diabetes, while the other remains perfectly healthy.

Identical twins have identical genes, because they are born of an embryo that splits at a very early stage in development. Such twins are often indistinguishable in outward appearance. But over the course of time they may experience radically dissimilar health.

Most scientists have assumed that environmental and lifestyle differences cause such divergence. These things trigger chemical reactions that affect our DNA and the proteins entwined with our DNA, called histones. One such reaction, known as methylation, influences the expression of genes and so can have an impact on health.

"Most people had the hypothesis that changes in DNA methylation are effected by the environment," says lead author Mario Fraga of the Spanish National Cancer Centre in Madrid. "This is the first time that somebody has demonstrated that this is the case." The findings appear in the Proceedings of the National Academy of Sciences¹.

Variations on a theme

To assess the variability in how genes are expressed between identical twins, the researchers studied genetic material from 40 pairs, ranging in age from 3 to 74 years old. They then assessed the amount of methylation of the DNA. The resulting computer-generated images highlights areas with significant differences in methylation.

The degree of chemical modification of DNA and its accompanying histones varied significantly between twins in a third of the pairs overall. But the older the twins were, the greater was the variability. Among the participants older than 28 years, chemical modification of DNA was significantly different in more than 60% of twin pairs.

Such changes can easily affect susceptibility to disease. The team identified one case in which a man with diabetes had an associated gene activated by a chemical change, where his healthy twin did not.

The study also found that the more time twins had spent apart, the more their patterns of gene activation differed. This further supports the notion that environmental factors exert a strong influence on genetic expression.

The team says that similar studies might be helpful in weeding out how much chemical influences on our genes affect risk factors for diseases. "This could be the way to identify the role of the methylation of genes," says team member Manel Esteller, also of the Spanish National Cancer Centre. 

Spanish National Cancer Centre, Madrid

• References

  1. Fraga M. F., et al. PNAS, published online, doi:10.1073/pnas.0500398102 (2005).