We generally think of monozygotic twins as natural clones , which are identical twins. Early in development, the embryo divides, separates, and produces two groups of cells whose genes are identical, each of which will grow into a different but the same baby.
The results of a new study published in Nature indicate that cell assignment during development shapes genomic differences between monozygotic twins. But how relevant is this to determining that the twins are not identical?
Monozygotic twins
Monozygotes are so similar that, even in 2009, in Germany, the arrest warrant for two of them was lifted as it was not possible to prove who had been the author of a jewelery theft in Berlin given their extraordinary resemblance (DNA included). But perhaps a small variation in the environment can produce very large effects on the phenotype (or vice versa), like the butterfly that flaps its wings at one end of the world and, by way of birlibirloque, ends up generating hurricanes at the other end.
But before the twins are born, we can take into account other important aspects that could undermine the common assumption that the sequences of the genomes of monozygotic twins are almost identical . In fact, there is a paucity of studies characterizing the genomic differences between these twins.
Thus, the average number of differences between the genomes of monozygotic twins is unknown. Furthermore, the types of mutations that lead to these differences and their timing are unknown. That is what the aforementioned study has tried to elucidate .
To estimate the number and timing of mutations that differ between monozygotic twins, postzygotic mutations present in the somatic tissue of one of the twins , but not the other, were looked for and timed by comparing whole genome sequencing data ( WGS) of monozygotic twins, their offspring, spouses, and parents.
It was then shown that monozygotic twins differ on average by ** 5.2 early developmental mutations ** and that approximately 15% of monozygotic twins have a substantial number of these early developmental mutations specific to one of them.
CpG> TpG mutations increased in frequency with embryonic development, coinciding with an increase in DNA methylation. Thus, the results indicate that cell assignment during development shapes genomic differences between monozygotic twins.
However, some clarifications must be made regarding these findings .
Details on these results
This study is one of hundreds of articles by deCODE (DEcentralized Citizen Owned Data Ecosystem), which have repeatedly shown how deep you can still go into human biology when you have the genomic sequence of an entire country .
The authors studied a subset of de novo mutations (a de novo mutation is a mutation that appears for the first time in a family, neither parents nor grandparents present this genetic alteration) that arise after the formation of the zygote (that is, after of the fusion of the sperm and the ovum).
Most de novo mutations are pre-zygotic and are present in sperm or egg. The authors report 5.2 post-zygotic mutations in 15% of the twins. This is ~ 0.1% of the total de novo mutation rate, which is 74 per individual .
We must bear in mind that a human being has six billion base pairs (considering the diploid genome). Consequently, the post-zygotic mutation rate is 5.2 / 6e09 \ u003d 8.6e-10, which amounts to a mere drop in the ocean of the genome .
Pre-zygotic mutations are less random as they are associated with the sex and age of the parents. But, post-zygotic mutations are likely to occur by chance .
Therefore, most of the reported large-effect associations for de novo mutations are likely due to precigotic mutations. The Nature study shows nothing about the pathogenicity or phenotypic effects of post-zygotic mutations .
Given this background, claiming that the findings of this study question the validity of twin-based heritability studies is unwarranted. Identical twins remain essentially identical in their genomic sequence .