Identical twins form the same egg and get the same genetic material from their parents – but that does not mean that they are genetically identical by the time they are born.
This is because so-called identical twins pick up genetic mutations in the uterus as their cells weave new parts of DNA and then divide into more and more cells. According to a new study, pairs of twins averaged an average of 5.2 mutations that occur early in development.
“One particularly surprising observation is that in many twin pairs, some mutations are carried by almost all cells in one twin, but in the other are completely absent,” said Ziyue Gao, an assistant professor of genetics at the University of Pennsylvania, who was not involved in the research, said in an email.
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The authors of the study estimate that one twin in about 15% of identical twin pairs has a “significant” number of mutations that the other does not share.
“It could be about 10 to 15 mutations,” says senior author Kari Stefansson, CEO of deCODE genetics, a subsidiary of biogenic company Amgen that studies the human genome. The study did not specify where in the genome these mutations occur, or whether they mostly occur in genes encoding specific types of proteins; it could be an area of future research, Stefansson said.
Gemini occurs when a single fertilized egg, called a zygote, divides and gives rise to two separate embryos; it usually occurs between one and seven days after fertilization, Stefansson said: although in rarer cases, twins can occur between Day 8 and 13.. The later the cleavage occurs, the more cells will accumulate when the twins separate.
Thus, if one twin has many mutations that the other does not have, it is possible that the siblings separated very early on. development, shortly after their shared egg was first divided into two separate cells, Gao said.
Alternatively, the egg may have split after a dozen cells have accumulated, but the group of cells did not divide evenly. Instead, one twin (i.e., half of the zygote) may have had a bunch of cells that mostly flowed from one parent’s cells, and therefore had common mutations, while the other twin had a bunch of cells that did not have the mutations. did not, she said.
“Some of them are probably insignificant … and some can lead to disease,” Stefansson said. In twin studies, which scientists use to investigate whether genetics or the environmental factors have more influence on a given trait, ‘we will have to account for the influence of these mutations,’ he said.
The new study, published January 7 in the journal Natural genetics, presents this unique snapshot of the early development because the authors did clever detective work using DNA from three generations of people.
These individuals included 387 pairs of identical twins and two sets of triplets, as well as their parents, spouses, and children. (The triplets were also monozygotic, meaning they were split from the same egg.) By sequencing the entire genome of all these relatives, the team was able to detect which mutations appeared in which twins, and which of the mutations then passed on to the offspring of the twins are transferred. .
If a mutation is passed down through several generations, it indicates that it is a germline mutation – one that occurs in the eggs, sperm and their progenitors. If the same mutation also occurs in the somatic (non-reproductive) cells of the parent, the mutation is likely to occur during their early development, say the authors.
This is because no cells have yet been placed in the first few weeks after fertilization to become germ cells, so that all cells can inherit the same mutations. After cells differentiate into germ and somatic cells, new mutations occurring in the somatic cells will not be passed on to the person’s children, whereas new mutations in the germ cells would do so. according to the National Cancer Institute.
Thus, “when such a mutation is found in the blood of a twin and passed on to their offspring, this mutation occurred during their early development,” when all cells were closely related, Gao said.
In addition to detecting mutations between generations, the authors looked for mutations that are shared within a twin set but do not occur uniformly in all of their cells. This phenomenon, known as mosaic, suggests that the mutation occurred after the egg was fertilized, but before the egg tore apart, as both siblings carry the peculiarity, Gao said.
Using both of these methods, the team was able to determine which mutations appeared in this narrow window of early development, and how often one twin had a mutation that the other did not. In short, one cannot assume that identical twins have the same DNA, they found.
One limitation of the study is that the authors collected DNA from cheek swabs and blood samples, but they did not collect any DNA from, for example, sperm or eggs, Gao said. If more tissues are sequenced, the authors are likely to identify more embryonic mutations and be better able to determine the mutations up to a certain stage of development based on their frequencies in different tissues, she noted.
In addition, the authors noted that they do not know which twin shares an amniotic fluid sac, placenta or chorion – the membrane that gives rise to the fetal part of the placenta. With the information, they were able to determine whether the share of these structures is at all related to the number or timing of genetic mutations in early development.
For now, the takeaway from the current study is that scientists should not assume that identical twins share 100% identical DNA; such assumptions can lead to them overestimating the impact of the environment, while a genetic mutation can in fact be the source of a particular disease or trait, Stefansson said.
“However, such genomic differences between identical twins are still very rare, in the order of a few differences in 6 billion base pairs,” with base pairs being the building blocks of DNA, Gao said. It is unclear how many of these small mutations result in a functional change that alters the functioning of the cell, and in general: “I doubt whether these differences will make a significant contribution to the phenotypic contribution. [or observable] differences in twin studies, ”she added.
Originally published on Live Science.