Identical twins may look alike, but their DNA is not the same as long thought, a new study finds. Moreover, each twin grows more genetically distinct over time. Aside from maybe giving forensic investigators a way to tell which twin committed a crime, these recent findings highlight just how changeable human genomes might really be, twins or not. Identical, or monozygotic, twins result when a fertilized egg, or zygote, splits in two. Because they derive from the same cell, such twins are generally assumed to be physically identical except for features shaped by environmental factors, such as fingerprints, and by womb conditions. At times the physical differences between monozygotic twins can be profound: one may manifest a disease such as diabetes and the other not. To see if genetic changes might underlie these disparities, molecular geneticists Jan Dumanski and Carl Bruder, both at the University of Alabama at Birmingham, and their colleagues investigated nine pairs of monozygotic twins, of which each set had one twin with Parkinson’s disease or a similar neurological disorder. The researchers found that all nine pairs showed genetic dissimilarities. Specifically, they discovered variations in the number of copies of genes. For instance, one twin might be missing a copy of a gene or have extra copies. Proceeding further, the investigators then looked at 10 pairs of healthy monozygotic twins with no significant visible differences between them. Unexpectedly, in one pair they confirmed that one twin was missing a gene-laden section of chromosome 2 that the other twin had, and preliminary findings suggested eight other pairs had copy number variations as well. “I can’t tell you what a shock that was,” Bruder recalls of their data in the March American Journal of Human Genetics. Furthermore, Bruder notes the genome analysis methods they used could find only relatively large changes, those that were roughly 150,000 DNA bases in size. He suspects that higher-resolution techniques will reveal that all monozygotic twins have copy number changes. These variations generally occur when double-stranded DNA breaks—the repair process may leave out genes or insert extra copies. In the twin with the loss in chromosome 2, only about 75 percent of blood cells had this deletion. The fractional aspect suggests that this copy number change happened relatively late in life, because alterations early in embryonic development would be expected to affect entire tissues. It remains uncertain, however, when and how often these changes occur. Although monozygotic twins may not be perfectly genetically identical, they still are nearly so, Bruder emphasizes. Hence, twin studies—in which identical twins are compared to look for differences arising from environmental influences—should continue to have their uses. So hunting down genetic differences between twins could greatly help in identifying genes linked to diseases. “When you look between people who aren’t twins who have a disease or don’t, there are so many other differences you have to sort through,” Bruder explains. “But with twins, it’s much easier to find what’s different.” If anything, twin studies might now find use in discovering how environmental factors can alter one’s genome, suggests Charles Lee, director of cytogenetics at the Dana-Farber/Harvard Cancer Center. The fact that even monozygotic twins diverge genetically over their lives “shows us how much more dynamic the genome is than we thought—it’s changing all the time, for good or for not,” Bruder says. He and his colleagues are now investigating whether all of an individual’s cells are genetically identical or whether, like twins, they diverge, making each of us mosaics of slightly different genomes.
Identical, or monozygotic, twins result when a fertilized egg, or zygote, splits in two. Because they derive from the same cell, such twins are generally assumed to be physically identical except for features shaped by environmental factors, such as fingerprints, and by womb conditions.
At times the physical differences between monozygotic twins can be profound: one may manifest a disease such as diabetes and the other not. To see if genetic changes might underlie these disparities, molecular geneticists Jan Dumanski and Carl Bruder, both at the University of Alabama at Birmingham, and their colleagues investigated nine pairs of monozygotic twins, of which each set had one twin with Parkinson’s disease or a similar neurological disorder. The researchers found that all nine pairs showed genetic dissimilarities. Specifically, they discovered variations in the number of copies of genes. For instance, one twin might be missing a copy of a gene or have extra copies.
Proceeding further, the investigators then looked at 10 pairs of healthy monozygotic twins with no significant visible differences between them. Unexpectedly, in one pair they confirmed that one twin was missing a gene-laden section of chromosome 2 that the other twin had, and preliminary findings suggested eight other pairs had copy number variations as well. “I can’t tell you what a shock that was,” Bruder recalls of their data in the March American Journal of Human Genetics.
Furthermore, Bruder notes the genome analysis methods they used could find only relatively large changes, those that were roughly 150,000 DNA bases in size. He suspects that higher-resolution techniques will reveal that all monozygotic twins have copy number changes. These variations generally occur when double-stranded DNA breaks—the repair process may leave out genes or insert extra copies.
In the twin with the loss in chromosome 2, only about 75 percent of blood cells had this deletion. The fractional aspect suggests that this copy number change happened relatively late in life, because alterations early in embryonic development would be expected to affect entire tissues. It remains uncertain, however, when and how often these changes occur. Although monozygotic twins may not be perfectly genetically identical, they still are nearly so, Bruder emphasizes. Hence, twin studies—in which identical twins are compared to look for differences arising from environmental influences—should continue to have their uses. So hunting down genetic differences between twins could greatly help in identifying genes linked to diseases. “When you look between people who aren’t twins who have a disease or don’t, there are so many other differences you have to sort through,” Bruder explains. “But with twins, it’s much easier to find what’s different.” If anything, twin studies might now find use in discovering how environmental factors can alter one’s genome, suggests Charles Lee, director of cytogenetics at the Dana-Farber/Harvard Cancer Center.
The fact that even monozygotic twins diverge genetically over their lives “shows us how much more dynamic the genome is than we thought—it’s changing all the time, for good or for not,” Bruder says. He and his colleagues are now investigating whether all of an individual’s cells are genetically identical or whether, like twins, they diverge, making each of us mosaics of slightly different genomes.
