July 29, 2010 Leave a comment
DNA sequence is just a starting point
Identical twins are identical only in that their DNA is the same. In what might be an argument against cloning yourself or a pet hoping to get an identical reproduction, scientists have found that having an identical genetic code does not translate into being exactly alike. We have long known that identical twins do not always share the same health fate, for example. One twin can have schizophrenia while another twin may never develop it. Or one twin might develop cancer or diabetes, while the other remains disease-free, even though there can be a strong genetic component to all of these disorders.
So a burning question in the field of genetics and disease has been identifying the difference between a twin who gets a disease and one who does not. A strong candidate mechanism has been the process of genomic modification in which molecules attached to the DNA can silence a gene or turn it on. Typically, methyl groups attached to DNA will make the code unavailable, and acetyl groups attached to the histone proteins that support DNA will ensure that the code is used.
Chemical tags modify DNA sequences
This process of genomic regulation is involved in some interesting aspects of biology. For example, methylation is the hallmark of genomic imprinting, in which each set of genes we inherit from our parents comes with its own special pattern of methylation. The way some genetic disorders manifest can be traced to genomic imprinting. In Prader-Willi syndrome, a person inherits a paternal mutant allele and manifests characteristic symptoms of the disorder, which include obesity and intellectual disability. But people who inherit the same mutant allele from the mothers will instead have Angelman’s syndrome, in which they are small and gracile, have a characteristic elfin face, and also have intellectual disability. Modification from methyl or acetyl groups, also called epigenetic modification, plays a role in dosage compensation for the X chromosome. Women, who have two X chromosomes, shut most of one down through methylation to produce an X chromosome gene dosage like that of men, who have a single X.
Twinning: Nature’s clones
Identical twins have identical DNA because they arise from a single fertilized egg. The egg divides mitotically into two identical cells, and then each cell, for reasons we don’t understand well, resets the developmental process to the beginning and develops as a new individual. The process of twinning carries interesting implications for bioethics, cloning discussions, and questions about when life begins, but it also has helped us tease apart the influences of genetics and environment. A recent study examining life history differences and differences in epigenetic modification in 80 pairs of twins ranging in age from 3 to 74 has revealed some fascinating results that have implications for our understanding of nature vs. nurture and our investigations into the role of epigenesis in development of disease.
You are what you do to yourself
The older the twins were, the more differences researchers found in methylation or acetylation of their DNA and histones. For twins raised apart, these differences were even more extreme. Researchers also concluded that environmental influences, such as smoking, diet, and lifestyle, may have contributed to the differences in the twins’ epigenetic modifications. The three-year-old twins were almost identical in their methylation patterns, but for twins older than 28 years, the patterns were significantly different for 60 percent of the pairs.
These results have major implications for our understanding of disease. For example, we can use this knowledge to identify genes that are differently methylated in people with and without a disorder and use that as a lead in identifying the genes involved in that disease state. We also may be able to pinpoint which environmental triggers result in differential methylation and find ways to avoid this mechanism of disease.