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Same Difference: Twins' gene regulation isn't identical

Christen Brownlee

Although identical twins have identical DNA, they often harbor clear-cut differences: slight variations in appearance or stark distinctions in disease susceptibility, for example. Scientists have suggested that the interplay between nature and nurture could explain such differences, but the mechanism has been poorly understood.

A new study suggests that as identical twins go through life, environmental influences differently affect which genes are turned on and which are switched off.

Called epigenetic modification, such gene activation or silencing typically stems from two types of chemical groups that latch on to chromosomes as charms attach to a bracelet, says Manel Esteller of the Spanish National Cancer Centre in Madrid. Methyl groups that clip on to DNA tend to turn genes off. On the other hand, acetyl groups attaching to histones, the chemical core of chromosomes, usually turn genes on.

Suspecting that such epigenetic differences might account for variations between identical twins, Esteller and his team focused on the two chemical changes. The scientists recruited 80 pairs of identical twins, ranging in age from 3 to 74, from Spain, Denmark, and the United Kingdom.

After extracting DNA from blood, inner-cheek cells, and biopsied muscle, Esteller's team screened the twins' genomes for differences in epigenetic profiles between members of a pair. The researchers also had each twin or, for children, a parent answer a comprehensive questionnaire on the twins' health history and lifestyle, including diet, exercise habits, and alcohol or tobacco use.

In the youngest twins, the scientists found relatively few epigenetic differences. However, the number of differences increased with the age of the twins examined. The number of epigenetic differences in 50-year-old twins was more than triple that in 3-year-old twins. Esteller's group also saw especially large epigenetic differences between twins who had spent most of their lifetimes apart, such as those adopted by different sets of parents at birth, the team reports in an upcoming Proceedings of the National Academy of Sciences.

Esteller says that these results suggest that a person's environment—whether he or she is exposed to tobacco smoke, eats particular foods, or suffers an emotionally wrenching event, for example—may affect which genes are turned on or off and so how cells operate. Thus, nurture may have a heavy impact on an individual's nature.

"My belief is that people are 50 percent genetics and 50 percent environment," says Esteller. "It's important to remember that our genes give us features of who we are, but our environment can change how we are."

Arturas Petronis, who studies epigenetics at the Centre for Addiction and Mental Health in Toronto, agrees. He adds that the findings could also have wide-ranging health implications for people who aren't twins.

"About 90 percent of diseases don't follow [simple] rules for inheritance," says Petronis. "By investigating epigenetic changes, to some extent we can understand how environmental factors affect human health."

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References:

Fraga, M.F. … and M. Esteller. In press. Epigenetic differences arise during the lifetime of monozygotic twins. Proceedings of the National Academy of Sciences. Abstract.

Further Readings:

Bjornsson, H.T., M.D. Fallin, and A.P. Feinberg. 2004. An integrated epigenetic and genetic approach to common human disease. Trends in Genetics 20(Aug. 1):350–358. Abstract.

Fraga, M.F. … and M. Esteller. 2005. Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nature Genetics 37(April):391–400. Abstract.

Rideout III, W.M., K. Eggan, and R. Jaenisch. 2001. Nuclear cloning and epigenetic reprogramming of the genome. Science. 293(Aug. 10):1093–1098. Abstract.

Sources:

Manel Esteller
Spanish National Cancer Centre (CNIO)
Melchor Fernandez Almagro 3
28029 Madrid
Spain

Andrew P. Feinberg
Departments of Medicine, Molecular Biology and Genetics, and Oncology
Johns Hopkins School of Medicine
720 Rutland Avenue
Baltimore, MD 21205

Arturas Petronis
Neurogenetics Section
Centre for Addiction and Mental Health
250 College Street
Toronto, ON M5T 1R8
Canada


From Science News, Volume 168, No. 2, July 9, 2005, p. 19.