How do genetics work in identical twins

Identical twins: But there are differences in DNA

Not identical: Even identical twins do not always have the same genetic make-up. Even in the early embryonic stage, mutations occur in the DNA that can occur in one twin and not in the other. On average, 15 percent of identical twins carry such genetic differences, as researchers report in the journal "Nature Genetics". The amount of these mutational differences varies from a few to around 100.

According to popular theory, identical twins have the same genetic make-up. Because they originated from the same fertilized egg cell, the DNA sequence of their cells is also identical. Nevertheless, there can be differences in appearance, handedness, behavior or health development among these twins. The main reasons for this are environmental influences, but also epigenetic deposits on the DNA that change gene activity.

Gene comparison in 387 twins

Identical twins do not always have to match genetically, as researchers working with Hakon Jonsson from deCODE Genetics in Iceland have now discovered. For their study, they examined 387 identical pairs of twins and their families, whether and how much their DNA differs and whether these differences occur in both body cells and germ cells.

Such differences between identical twins can arise when mutations occur in cell lines of one twin embryo but not in those of the other. There is enough time for this because the embryos separate in the first few days after fertilization. "Until now, the average number of differences in the genomes of monozygotic twins was unknown, and what mutations these are and when they arise was not known," the researchers explain.

15 percent of the twins have mutational differences

Their analyzes showed that around 15 percent of the identical twins had genetic differences caused by mutations. The number of these mutations varies widely, ranging from just one to 100 genetic changes. On average, the genetic differences for all the twin pairs examined are 5.2 mutations.

The comparisons also provided clues as to when these mutations occurred in the twins. For example, if all body cells and also the germ cells of a twin have a mutation that the sibling does not have, then this genetic change must have occurred at a very early embryonic stage - within the first one to two weeks after fertilization. Because at this point in time, the cell line of the germ cells separates from that of the body cells, as the researchers explain.

Mutation shortly after fertilization

In some cases, the mutation occurs in a cell of the still common zygote. When this cell then separates and the twin emerges from it, only he gets the mutation. Mutations that occur across the body and are inheritable in the twin subjects must come from a single cell line that was only formed five to six mitoses after the zygote was formed, ”say Jonsson and his team.

But even after the two twins have separated, further mutations can occur. The sooner this happens, the more widespread the mutation is in the carrier's organs and tissues. There are also cases where a twin takes both mutated and non-mutated cells with it when the embryos are separated. Then only some of its tissues share the mutations with its twin.

Influence of mutations underestimated

"So far, phenotypic differences in monozygotic twins have generally been attributed to environmental influences," say Jonsson and his team. “It was assumed that the contribution from mutations differing in these twins would be negligible.” But the new results suggest that this need not necessarily be the case.

This is also important for twin research in medicine. Because comparisons of identical twins are often used there to determine the extent of the hereditary components in diseases. "The differences that have now been identified indicate that the contribution of such sequence changes to disease development was underestimated in most models," they say. (Nature Genetics, 2021; doi: 10.1038 / s41588-020-00755-1)

Source: Nature

January 12, 2021

- Nadja Podbregar