Identical twins do not always have identical genes, study shows – Business Insider – Business Insider

  • A study published in Nature found that identical twins — twins that come from a single fertilized egg — aren’t genetically identical.
  • Instead, they differ by an average of 5.2 genetic mutations that arise in the first week of their development.
  • These genetic differences could be enough to lead one twin to develop a disorder like neonatal cancer, while the other twin remains healthy.
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For decades, researchers believed that monozygotic twins — twins that form when a fertilized egg splits in two — were born with essentially the same genetic codes. Hence the common name for such pairs: identical twins.

But according to new research published in Nature, identical twins aren’t necessarily genetically identical. Rather, their genomes often differ in small but significant ways from the very first week of development.

For the study, scientists at deCODE genetics, an Icelandic biopharmaceutical company, sequenced the genomes of hundreds of pairs of identical twins. They found that on average, identical twins differed from each other by 5.2 mutations that arose in the early stage of growth.

kari stefansson
Kari Stefansson, CEO of deCODE genetics and the lead author of the Nature study.
Magnus Andersen/deCODE genetics

Kari Stefansson, a senior coauthor of the study and the CEO of deCODE genetics, said the findings suggest that scientists may have overestimated the role that non-biological factors play in developmental disorders like autism and neonatal cancer.

“If you take identical twins raised apart, and one has autism and the other does not, the classic interpretation has been that environment was the cause of autism,” Stefansson told Business Insider. “Our work shows it is dangerous to jump to that conclusion. You have to assume it exists because of a mutation found in one twin and not the other.”

Even small genetic tweaks at the earliest stages of development can trigger such conditions.

Mutations may not divide equally when a fertilized egg splits

The study authors sequenced the genomes of over 380 pairs of identical twins and two pairs of triplets, as well as their parents, spouses, and children. They used a technology called next-generation sequencing, which enables scientists to sequence an entire human genome within a single day. Before next-generation sequencing became widely available around 2005, it could take 10 years or more to sequence a genome. 

The researchers examined the twins’ families in order to pinpoint when specific early genetic mutations arose — whether they developed in the parents’ sperm and egg cells (these are called hereditary mutations), or emerged in a fertilized egg’s cells once it started to develop and grow (somatic mutations).

“As cells replicate, and replicating machinery makes a copy of the genome — it’s not flawless,” Stefansson said. “Mutations also accumulate in the eggs of the mother and sperm of the father.”

bacterium2
Transmission electron microscopy image of a D. radiodurans cell splitting.
Ott et al./Microbiome, 2020

Somatic mutations arise when a cell makes an error copying its DNA as it splits. While that mutation gets passed along to every resulting cell, it isn’t present in every cell of the body. 

Hereditary mutations, by contrast, are present in the very first cells that make up a developing embryo, which mean the mutations get passed to each cell. Since identical twins split from the same egg, they should both share any hereditary mutations from their parents’ sperm and egg.

After an egg is fertilized and becomes a zygote, somatic mutations can begin popping up within days, once the zygote’s cells begin dividing to form a mass of cells called a morula. Mutations can also occur when the morula grows into a blastocyst, an early-stage embryo, less than a week into development.

A fertilized egg can split in two, giving rise to twins, before the zygote becomes a morula, or around when it becomes a blastocyst.

But the study authors found that just because a zygote splits, it doesn’t mean hereditary mutations get passed along equally to both halves.

“They can go into both, or one, or neither one. That gives us the opportunity to find the mutations that separate identical twins,” Stefansson said.

In about 15% of the twin pairs studied, one twin had a significantly higher number of early developmental mutations than the other. In some pairs, both twins had very few mutations overall. 

“Coincidence, or stochastic mechanism, decides what happens to each twin,” Stefansson said. 

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Identical twins do not always have identical genes, study shows – Business Insider – Business Insider

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