Identical twins form from the same egg and receive the same genetic material from their parents – but that does not mean that they are genetically identical at birth.
That’s because so-called identical twins pick up genetic mutations in the uterus, as their cells weave new strands of DNA and then divide into more and more cells. On average, twin pairs have genomes that differ by an average of 5.2 mutations that occur early in development, according to a new study.
“A particularly surprising observation is that in many pairs of twins, some mutations are carried by almost all cells in one twin, but are completely absent in the other,” said Ziyue Gao, assistant professor of genetics at the University of Pennsylvania, who was not involved. with the research, said in an email.
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The study authors estimate that in about 15% of identical twin pairs, one twin carries a “substantial” number of mutations that the other does not share.
“This can be up to about 10 to 15 mutations,” said senior author Kari Stefansson, CEO of deCODE genetics, a subsidiary of the biopharmaceutical company Amgen that studies the human genome. The study did not specify where in the genome these mutations occur, or whether they arise mainly in genes that code for specific types of proteins; this could be an area of future research, said Stefansson.
Twinning occurs when a single fertilized egg, called a zygote, divides and gives rise to two separate embryos; this usually occurs between one and seven days after fertilization, Stefansson said, although in more rare cases, twinning can occur between days 8 and 13. The later the division occurs, the more cells will have accumulated when the twins separate.
So, when one twin has many mutations that the other does not, it is possible that the siblings broke up very early in development, just after the shared egg divides into two separate cells, said Gao.
Alternatively, the egg may have divided after a dozen or more cells have accumulated, but that cluster of cells has not divided equally between them. Instead, one twin (that is, half of the zygote) may have grabbed a cluster of cells that originated mainly from a parent cell and therefore carried common mutations, while the other twin received a cluster of cells without those mutations , she said.
“Some of them are probably irrelevant … and some of them can lead to disease,” said Stefansson. Inside twin studies, which scientists use to explore whether genetics or environmental factors have more influence on a given trait, “we will have to take into account the influence of these mutations,” he said.
The new study, published on January 7 in the journal Nature Genetics, offered this unique snapshot in early development because the authors did smart detective work using DNA from three generations of people.
These individuals included 387 pairs of identical twins and two pairs of triplets, as well as their parents, spouses and children. (The triplets were also monozygous, meaning they separated from the same egg.) By sequencing entire genomes of all of these family members, the team was able to track which mutations appeared in which twins and which of those mutations were then transmitted to the twins’ children. .
If a mutation is transmitted over several generations, it indicates that it is a germline mutation – which appears in the eggs, sperm and their precursors. If that same mutation also appears in the somatic (non-reproductive) cells of the father, that mutation probably appeared during his early development, the authors note.
That’s because, in the first few weeks after fertilization, no cells have been programmed to become germ cells yet, so all cells can inherit the same mutations. Once the cells differentiate into germ and somatic cells, new mutations that appear in the somatic cells will not be transmitted to the person’s children, while new mutations in the germ cells, according to the National Cancer Institute.
So, “if such a mutation is found in the blood of a twin and transmitted to his offspring, that mutation occurred during early development,” when all the cells were closely related, said Gao.
In addition to tracking mutations between generations, the authors looked for mutations that were shared by a set of twins, but were not uniformly present in all cells. This phenomenon, known as mosaicism, indicates that the mutation occurred after fertilization of the egg, but before the egg broke, as both brothers carry the peculiarity, said Gao.
Using both methods, the team was able to identify which mutations arose in that narrow window of initial development and how often one twin had a mutation that the other did not. In short, identical twins cannot be presumed to share identical DNA, they found.
A limitation of the study is that the authors collected DNA from cheek swabs and blood samples, but did not collect DNA from, say, sperm or eggs, said Gao. If more tissues are sequenced, the authors are likely to identify more embryonic mutations and be better able to identify these mutations at a given stage of development based on their frequencies in different tissues, she noted.
In addition, the authors noted that they did not know which twins shared an amniotic sac, placenta or chorion – the membrane that gives rise to the fetal part of the placenta. With this information, they could determine whether the sharing of these structures is related to the number or timing of genetic mutations at the beginning of development.
For now, the conclusion of the current study is that scientists should not assume that identical twins share 100% identical DNA; such assumptions may lead them to overestimate the influence of the environment, when in reality, a genetic mutation may be the source of a particular disease or trait, said Stefansson.
However, “these genomic differences between identical twins are still very rare, on the order of some 6 billion base pair differences,” with base pairs being the building blocks of DNA, Gao said. It is not clear how many of these small mutations would result in a functional change that alters the cell’s functioning and, in general, “I doubt that these differences have an appreciable contribution to the phenotype [or observable] differences in twin studies, “she added.
Originally published on Live Science.