Despite originating from the same fertilized egg, about 90% of identical twins have differences in genes that arose from mutations in utero, while 15% of pairs had a substantial number of genetic differences between them, according to new research. It raises questions about the results of scientific twin studies investigating the question of “nature versus nurture” that assume otherwise.
Previous research on the subject had found some genetic differences between identical twins but left an incomplete picture. In a study published last week in Nature Genetics, biopharmaceutical company deCODE genetics was the first to determine the prevalence of genetic differences between identical twins and how they arise during human development.
Kari Stefansson, the CEO of deCODE genetics and the paper’s senior author, said his company pursued the research for its interest in genetic mutations found in children but not their parents, as well as in human heritability and diversity more broadly.
“Identical twins are at the one end of the spectrum of human diversity,” said Stefansson, who was previously a professor at the University of Chicago and Harvard University. “The difference between them is so little you can hardly call it diversity, and we basically decided to look at it because we were interested in seeing whether we would be able to find any mutations that separate them.”
Identical siblings are formed when a fertilized egg, or zygote, splits into multiple embryos, which then grow into individual fetuses. As the cells divide, their DNA replication systems occasionally make mistakes and create mutations, which are passed down to other cells as divisions continue. DeCODE genetics found mutations that occurred after the zygote split, leading to a genetic difference between identical twins.
The Icelandic company’s researchers analyzed the genomes of 381 identical twin pairs and 2 identical triplets as well as their parents, children and spouses. Taking advantage of the genetic information from their families, they concluded there was an average of about 5 genetic differences between the identical siblings. Only 38 of the pairs had truly identical DNA, while 39 had more than 100 differences. About 15% had a “substantial number” of differences that were found in most of their cells.
The number of genetic differences is minuscule compared with the approximately 3 billion base pairs in human DNA, but Stefansson noted that they encompass about 8% to 9% of the mutations the average person accumulates in utero.
The researchers found that mutations could be distributed within and between identical twins differently depending on when during development they occur. Mutations from before they separate could become present in either both twins or only one. The timing and location of a mutation also determines whether it is present in all of a twin’s cells or just some of them.
“When you look at the whole dataset, it looks almost like that what decides what cell leads to an individual is dictated by chance alone,” Stefansson said.
The team found a similar phenomenon in a set of identical triplets, in which two of the siblings shared two mutations not found in the third, who also had a unique mutation of their own. The more similar triplets were likely descendants of the same cell during fertilization, the researchers wrote, while the third descended from a different set of cells.
Founded by Stefansson in 1996, deCODE genetics is best known for creating a national genome database for Iceland that currently contains information on two-thirds of the island nation’s 361,000 inhabitants and half of the roughly 1.8 million people who have ever lived on the island. The project, known as Islendingabok or “Book of Icelanders,” has been used to investigate the genetic aspects of many diseases, conditions and traits and used as a model for other national genome projects.
Many scientific studies have used identical twins as subjects to rule out genetic explanations of their differences — which must be caused by their environments, the assumption goes. But deCODE genetics’ findings confirmed that the genes of twins often differ and challenged the assumption. Stefansson said future twin studies should include a full sequencing of their genomes, a standard he said had been previously discussed but is now “probably established once and for all.”
“The paper we published ... shows that you have to assume that the possibility exists that the differences you see between identical twins are not environmental,” he said.
Stefansson’s team plans to explore how gene mutations in twins are expressed, an investigation the CEO said would require a tenfold increase in subjects from the previous paper.
The article, “Differences between germline genomes of monozygotic twins,” was published Jan. 7 in Nature Genetics. The authors of the study were Hakon Jonsson, Hannes Eggertsson, Olafur Stefansson, Gudny Arnadottir, Ogmundur Eiriksson, Florian Zink, Einar Helgason, Ingileif Jonsdottir, Arnaldur Gylfason, Adalbjorg Jonasdottir, Aslaug Jonasdottir, Doruk Beyter, Gudmundur Norddahl, Olafur Magnusson, Gisli Masson and Patrick Sulem, deCODE genetics; Bjarni Halldorsson, Unnur Thorsteinsdottir, Agnar Helgason, Daniel Gudbjartsson and Kari Stefansson, deCODE genetics and University of Iceland; and Erna Magnusdottir and Thora Steingrimsdottir, University of Iceland. The lead author was Hakon Jonsson.