Research published on January 7 in the journal Nature Genetics shows that identical twins differ by an average of 5.2 genetic mutations. The authors argue that these small differences between twins’ genetic code could change how scientists study human development.
The study of 381 pairs of identical twins and two sets of identical triplets found that only 38 were genetically identical, Tina Hesman Saey reports for Science News. Most had just a few points of genetic mismatch, but 39 had more than 100 differences in their DNA. The findings could impact future studies of the ways that the environment affects disease and human development. In such studies, scientists often assume that pairs of identical twins have identical DNA, so their differences can be explained by the environments they grew up in.
“Before you can make that interpretation, you’d better make sure that one of them does not have a de novo [randomly introduced] mutation in an important gene that the other one does not,” says Kari Stefansson, CEO of DeCODE Genetics and lead author of the new study, to the Scientist magazine’s Catherine Offord. “So this certainly places a new kind of burden on those who use identical twins to establish the separation between nature and nurture.”
The researchers sequenced the full DNA code of cells found in cheek swabs and blood samples from not only the twins, but also their parents, their children, and their children’s other parent, Nicoletta Lanese reports for Live Science. With three generations of genetic information, the researchers could not only figure out where specific mutations appeared in the DNA code, but when, by determining at what stage in their embryonic development the mutations occurred.
The genetic mutations observed in the study mostly involved a single building block of the DNA code, called a base, mistakenly swapped for a different one. In some cases, letters were either inserted or deleted. Working at the scale of a human genome, a few changes may not cause much of a difference.
"Such genomic differences between identical twins are still very rare,” says University of Pennsylvania computational biologist Ziyue Gao, who wasn’t involved in the study, to Live Science. The human genome is six billion base pairs long, and the study did not make it clear how many of the mutations would cause significant changes. She adds, “I doubt these differences will have appreciable contribution to phenotypic [or observable] differences in twin studies.”
The mutations covered in the study tend to appear while a cell is replicating, or dividing itself, to create more cells. During that process, the cell has to completely copy all six billion base pairs, and sometimes it makes mistakes. The cell has machinery to correct mistakes, but even those go wrong sometimes, leaving behind small typos. If such a typo is created in a bundle of cells early in human development, then when the bundle splits into two parts, the mutation might not reach both parts equally.
“We have found a twin pair where one of the twins has mutations in all cells of his body, and they are not found in any cell in the body of the other twin. That means basically that one of the twins is formed solely from the descendant of the cell where the mutation took place,” says Stefansson to the Scientist. “Then we have found twins when the mutation is found in all cells in the body of one of the twins, and in 20 percent of the cells in the body of the other twin. So one of the twins has just formed from the descendant of this one cell where the mutation happened, and the other is formed in part by descendants of that cells and in part by something else.”
The study compared the twins’ DNA to their parents and children to find out when the mutation happened during their development. If the mutation happened very early, then the mutation could be passed along to their children, because it would have ended up in their sperm or eggs. Mutations that happen later in embryonic development might only appear in a person’s non-reproductive cells.
Uppsala University geneticist Jan Dumanski tells the Associated Press’ Christina Larson that the study is “a clear and important contribution” to medical research.
Stefansson adds that the implications go beyond nature-and-nurture twin studies.
“This is not just a study that has relevance when it comes to understanding of the genetics, but also human development: How do we probe early human development in an ethical manner, a non-interventional manner? This is one way of doing that,” he says to the Scientist magazine. “We can begin to use the mutations to develop [an] understanding of how cells are allocated from the early embryo to develop the various organs in the body.”