“Identical twins” are not really identical! There, I said it. Comparing identical twins is akin to matching apples to pineapples instead of apples to apples. Each twin obviously has their own personality, viewpoints, fingerprints and footprints. Digging deeper, it is clear that “identical” twins do not have identical genomes, especially as time goes on.

Genomic differentiation (or somatic mutations for the science types) begins at conception/twinning and stops only once the twins reach the wrong side of the dirt. In one study, it was estimated 1 in 12,000,000 nucleotides of the twins’ genomes are already different at the embryonic stage (Li et al., 2014). We have also seen how different genetic analysis companies return very different genomic reports not only for identical twins, but sometimes even for the same person. Plus, genes can be turned off and on like light switches—this can happen while the twins develop in utero or as a response to their environment throughout life.

We also know that twins can have very different health outcomes. For instance, when one twin becomes afflicted with rheumatoid arthritis, the other twin stands at only a fifteen percent chance of getting the disease (Singer, 2006). In a study of 200,000 twins (both identical and non-identical), about one out of every three people developed cancer (Mucci et al., 2016). It turned out, however, to be very rare for both identical twins to get cancer, let alone the same cancer. Another group looked to see if new mutations or different gene “on and off” patterns were behind the onset of multiple sclerosis in one twin but not the other (Baranzini et al., 2010). To their amazement, in the sets of “identical” twins studied, the researchers could not pinpoint one set of genetic differences that explained why one twin got the disease and the other one did not.

We think the answer lies instead in the protein differences between people, and there is some evidence to support this viewpoint. In one example, a research team found proteomic differences in twins using a panel that focused on just 69 proteins (Kato et al., 2011). Imagine what they could have found if they had looked at 5,000? In another example, researchers found elevated levels of a particular protein in one member of an identical twin pair that could explain why he has severe kidney disease while his brother is perfectly healthy (Hall, 2018). In another study, scientists noted numerous protein differences between one twin who had an ischemic stroke and the other who did not (Vadgama, Lamont, Hardy, Nasir, & Lovering, 2019).

You may not be surprised to hear that identical twins are not that identical, but you are probably surprised to learn that protein differences may account for that disparity more often than genetic changes. So, we need to move beyond genes to understand diseases and – we hope – how to treat them or even prevent them.

 

References

Baranzini, S. E., Mudge, J., van Velkinburgh, J. C., Khankhanian, P., Khrebtukova, I., Miller, N. A., . . . Kingsmore, S. F. (2010). Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis. Nature, 464(7293), 1351-1356. doi:10.1038/nature08990

Kato, B. S., Nicholson, G., Neiman, M., Rantalainen, M., Holmes, C. C., Barrett, A., . . . Schwenk, J. M. (2011). Variance decomposition of protein profiles from antibody arrays using a longitudinal twin model. Proteome Sci, 9, 73. doi:10.1186/1477-5956-9-73

Li, R., Montpetit, A., Rousseau, M., Wu, S. Y., Greenwood, C. M., Spector, T. D., . . . Richards, J. B. (2014). Somatic point mutations occurring early in development: a monozygotic twin study. J Med Genet, 51(1), 28-34. doi:10.1136/jmedgenet-2013-101712

Mucci, L. A., Hjelmborg, J. B., Harris, J. R., Czene, K., Havelick, D. J., Scheike, T., . . . Nordic Twin Study of Cancer, C. (2016). Familial Risk and Heritability of Cancer Among Twins in Nordic Countries. JAMA, 315(1), 68-76. doi:10.1001/jama.2015.17703

Vadgama, N., Lamont, D., Hardy, J., Nasir, J., & Lovering, R. C. (2019). Distinct proteomic profiles in monozygotic twins discordant for ischaemic stroke. Mol Cell Biochem. doi:10.1007/s11010-019-03501-2