Identical twins carry a persistent epigenetic signature on their DNA

New leads in research into the origin of identical twins.

Identical (Monozygotic) Twins look remarkably alike; it can be difficult to tell them apart. Despite amazing progress in most areas of science, scientists still have no idea how they look so identical.

Monozygotic (MZ) twin births arise when the progeny of a single fertilized egg cell, the zygote, divides into two or more embryos early in development. Why and how often this happens is a long-standing enigma of human developmental biology. 

An international group of researchers led by Jenny van Dongen and Dorret Boomsma of the Vrije Universiteit Amsterdam (VU) has made an important discovery. They found a unique epigenetic profile in identical twins.

Scientists discovered that epigenetic information in the chromosomes differs between identical twins and others. However, these differences are not in the DNA code itself but small chemical marks associated with it.

For the study, scientists measured methylation levels at more than 400,000 sites in the DNA of more than 6,000 twins. They found 834 locations in the DNA where the methylation level was different in identical twins than in non-twins.

This signature spans regions near telomeres and centromeres, Polycomb-repressed regions and heterochromatin, genes involved in cell adhesion, WNT signaling, cell fate, and putative human metastable epialleles.

Professor Dorret Boomsma of the Netherlands Twin Register (VU) specialized in genetics, and twin studies, said, “This is a very big discovery. The origin and birth of identical twins have always been a complete mystery. It is one of the few traits in which genetics plays no or very modest role. This is the first time that we have found a biological marker of this phenomenon in humans. The explanation appears not to lie in the genome, but its epigenome.”

Professor Bruno Reversade of the Agency for Science, Technology, and Research (A*STAR) in Singapore: “This amazing finding is diagnostic; it brings hitherto unknown insights into the fabrics for MZ twinning. The next step will be to find out why this happens.”

The epigenome determines how genes are tuned and how strongly they are expressed. On the other hand, DNA methylation controls which genes are “on” and which genes are “off” in each cell of the body.

Dr. Jenny van Dongen, who leads the study, is a researcher at the Netherlands Twin Register (VU) specializing in epigenetics: “These locations in the DNA are involved in functions in early embryonic development. In addition to insights into the fabrics of monozygotic twins, our results may lead to a better understanding of congenital abnormalities that occur more often in monozygotic twins in the future.”

“A particularly surprising finding in this study is that we can determine from the epigenetic profile of a person whether he/she is an identical twin or has lost a monozygotic twin sibling early in pregnancy, also known as vanishing twin syndrome.”

Professor Nick Martin of the Queensland Institute of Medical Research, Brisbane, Australia, adds: “An international collaboration of twin researchers could have only done this study. It provides an exciting breakthrough. Instead of focusing on genomics, an epigenome-wide association study was done, comparing methylation levels at over 400,000 sites across the entire human genome in Dutch MZ twins and controls.”

Meta-analysis of these results points to unusual methylation patterns in genes involved in cell adhesion which might explain the spontaneous fission of an early developing embryo into two identical halves. This finding may also provide important clues to the origin of numerous congenital disabilities known to be strongly associated with MZ twinning.

Journal Reference:
  1. Van Dongen, J., Gordon, S.D., McRae, A.F. et al. Identical twins carry a persistent epigenetic signature of early genome programming. Nat Commun 12, 5618 (2021). DOI: 10.1038/s41467-021-25583-7

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