Identical twins are derived from the same fertilized ovum and, therefore, should be…well… identical, right? They look the same and often dress the same, especially as children, and many people often have a hard time distinguishing one twin from the other. They are indistinguishable by genetic testing.
However, identical twins are not always identical, as the authors of a recent letter to the editor of Forensic Science International Genetics point out (1).
In this letter, scientists proposed a thought experiment designed to discriminate between identical twins, also known as monozygotic twins, in a paternity dispute. With current paternity testing methods, which track the inheritance of short tandem repeat (STR) markers from father to son, there is no way to genetically differentiate one monozygotic twin from the other. Their STR profiles will be identical, so the alleged father could easily try to shift the responsibility to his twin brother. Current DNA testing would be unable to resolve these types of disputes except in very rare cases where there are unshared mutations at these loci.
While the probability of an unshared mutation at an STR locus is very low, the probability that there are unshared mutations throughout the entire genome is surprisingly high: Some DNA mutations will likely occur during the many cycles of DNA replication and cell divisions between embryogenesis and adulthood. Let’s review the numbers that Krawczak et al. outline in their letter: In >98% of pregnancies with monozygotic twins, duplication of the zygote occurs within the first week, so the embryonic cells have undergone <7 cell divisions at the time of twinning. Obviously, any mutations that occur prior to this point will be shared by the twins, while any mutations after this point will not be shared. By the end of the second week of pregnancy, each of the ~15,000 embryonic cells has replicated 7 or 8 times. Roughly one-third of the resulting cells will go on to form the mesoderm, one of the three primary germ cell layers in the early embryo, and a subset of these cells (approximately 50 cells) will migrate into the yolk sac, continue to divide 6 or 7 more times, then make their way into the embryonic gonads. Female germ cells divide only 13 times before they become arrested in the first meiotic division, but male germ cells will undergo another 365 rounds of cell division by the time the child reaches puberty and spermatogenesis begins. The misincorporation rate during each round of DNA replication is approximately 10–8 per nucleotide per generation, and for every 3 single-base substitutions, there will be about 1 small insertion or deletion. After doing the math, the authors estimate the probability that there will be at least one heritable mutation that differs between monozygotic twins at 83%, and the chance that two such mutations are present exceeds 53%.
Thus, most identical twins will have genetic differences that theoretically could be used to distinguish between them and identify the biological father in a paternity dispute. Looking for these differences is the equivalent of looking for a needle in a haystack. However, with more thorough genetic testing such as whole genome sequencing, which until recently was prohibitively time-consuming and expensive, scientists should be able to identify genetic differences and use them to resolve paternity cases that involve monozygotic twins.
- Krawczak, M. et al. (2011). How to distinguish genetically between an alleged father and his monozygotic twin: A thought experiment. Forensic Sci. Int. Genet. PMID: 22177714