Image courtesy of Pixabay.
The classic scientific debate on “nature vs. nurture” asks: to what extent do genetics shape our characteristics, and to what extent do our environments shape our characteristics? In pursuit of the answer, scientists historically studied identical twins, or monozygotic twins, who were widely believed to share the same DNA. To isolate differences associated with nature as opposed to nurture, these studies assumed that any differences in identical twins must have been due to the environment, as their genetic material would be the same.
However, new research from Hakon Jonsson and Erna Magnusdottir, as well as collaborators at deCODE genetics, the University of Iceland, and Reykjavik University, suggests otherwise. The team recently found that identical twins on average differ by 5.2 mutations from early in the life cycle. The study, which involved the genetic sequencing of almost fifty thousand people, further showed that, in fifteen percent of identical twins, one of the twins has a substantial number of mutations that the other does not have.
Beyond quantifying the average mutation differences between monozygotic twins, this study also looked into when the mutations occurred during development. Jonsson and the research team cleverly used information on early development, coupled with genetic sequencing of identical twins along with their parents, spouses, and children, to draw inferences surrounding the timing of mutations during development.
So, how exactly can researchers use the genetic sequences of these close contacts to decipher when mutations occurred? The answer relies on the very beginnings of the human life cycle. When an egg cell is fertilized, it becomes a single-celled zygote, composed of genetic material from both parents. Over time, the zygote divides and embeds itself into the uterine lining to form the blastocyst. After several weeks, some of the cells are designated to be germ cells, or sex cells. Sex cells are involved in passing genetic material on to offspring.
Twinning occurs when the single mass of developing cells splits into two identical masses, which eventually become the two twins. This process generally occurs early in development, much before the designation of germ cells.
The researchers used the development process coupled with genetic information from relatives of identical twins to determine at what point mutations occurred in development. For example, the researchers identified mutations in an identical twin and their offspring, but not in the twin’s spouse or twin counterpart. Of these mutations, the researchers then found that some were also present in somatic body cells of the twin. From the life cycle, the researchers could extrapolate that the mutation occurred after twinning, because the twin’s monozygotic counterpart didn’t have the mutation. Additionally, because the mutation was present in both somatic cells and germ cells, investigators inferred that the mutation likely occurred before the germ line cells were designated. If this wasn’t the case, the mutation would have been found in either somatic cells or germ cells, not both. The researchers used similar logic to identify at what point in development a variety of mutations likely occurred.
In addition to identical twins, the researchers also investigated a family with identical triplets in order to learn more about genetic variation. Specifically, this case study proved crucial in exploring cell allocation. Cell allocation is concerned with the designation of different cell types. For example, twinning may occur when a group of cells is designated and begins developing independently of existing cells. In the case of the triplets, researchers found that two of the triplets shared more mutations with each other than the third. The study pointed to cell lineage as a potential explanation: two of the triplets were likely “descended” from the same cell whereas the third triplet came from another set of cells that was allocated separately.
So where does this leave identical twin studies, which assume that these mutations are insignificant compared to environmental factors? Jonsson and the research team caution that the effects of these mutations have likely been underestimated when it comes to the development of certain diseases. However, even if nature vs. nurture identical twin studies are eventually retired from the field, studies involving twins still have their place: further work can be done with identical twin genetics to better understand early stages of human development.
Sources:Jonsson, H., Magnusdottir, E., Eggertsson, H.P. et al. (2021). Differences between germline genomes of monozygotic twins. Nat Genet, 53, 27–34. https://doi.org/10.1038/s41588-020-00755-1