Sci. Aging Knowl. Environ., 13 July 2005
Not Like the Other
Older identical twins acquire different chromosome marks
R. John Davenporthttp://sageke.sciencemag.org/cgi/content/full/2005/28/nf56
Hang around with identical twins long enough, and you'll spot nuances that distinguish them. The same holds true for their DNA, according to a new study. Researchers have found that as identical twins age, the patterns of chemical changes to their chromosomes grow increasingly dissimilar. The findings might explain why one twin doesn't always get the same diseases as her sibling.
Identical twins harbor the same genetic code because both grew from the same fertilized egg. They might look alike and finish each other's sentences, but each person is still unique. For instance, some diseases with genetic origins, such as leukemia and schizophrenia, often strike only one twin. Adding chemical tags to chromosomes can alter gene activity by modifying the structure of DNA, a phenomenon known as epigenetics, and these changes can spur tumors and other problems. Cancer researcher Manel Esteller of the Spanish National Cancer Center in Madrid and colleagues wondered how chromosome adornments morph as twins age.
To investigate, the researchers gathered DNA from 40 pairs of twins from 3 years to 74 years old. They tracked two kinds of chromosome markings: the addition of methyl groups to DNA and the attachment of acetyl groups to histones, the proteins around which DNA winds. Younger twins appeared as if they wore the same outfits: They sported similar degrees of methylation and acetylation on their chromosomes. Older twins didn't resemble each other as closely, as if they had different haircuts. One person might gain methyl groups while the sibling lost them, for instance. In addition, twins who reported spending more time apart exhibited greater differences than did duos who stuck together. That correlation suggests that the altered chemical patterns might result from different surroundings, Esteller says: "Epigenetics seems to be the link between nature and nurture."
The team next scrutinized particular chromosome regions and found that zones where one twin acquired more methyl groups tended to contain deactivated genes, consistent with conventional wisdom that this chemical tag shuts down DNA. Next, the researchers measured the activity of many genes using gene chips. They found that older twins displayed larger differences in gene activity than did younger twins. Moreover, pairs with the greatest variability in chromosome modifications exhibited the largest differences in gene activity. The findings suggest that identical twins amass dissimilar configurations of chemical groups on chromosomes, which might skew gene performance.
"The data suggest that epigenetic changes happen over time and in a dramatic way," says cancer researcher Andrew Feinberg of Johns Hopkins University in Baltimore, Maryland. He praises the researchers for assessing global changes to the genome. Next, they should probe specific genes more closely to deduce how the alterations modify cells and tissues. In addition, future studies should follow twins over time to bolster the findings, he says. The work doesn't just apply to twins. Epigenetic changes acquired over a lifetime could explain why some diseases such as Alzheimer's disease develop later in life, says Feinberg. Further work could reveal why no two people--not even twins--age identically.
July 13, 2005
Science of Aging Knowledge Environment. ISSN 1539-6150