We are more unique than we believe

Variations in the genome have a stronger effect than previously thought

The DNA of two humans differs only minimally - the influence of these differences, however, reaches amazingly far. © Thinkstock
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Influential differences: The fact that the genetic material differs from person to person is nothing new. However, one study now shows that the influence of these genetic variations seems to be much stronger than previously thought. Because of them, the proteins of two people differ on average by 20, 000 building blocks - and these variants affect the function of these proteins considerably, as the simulations of researchers reveal.

Our genetic manual covers three billion letters and would print some books. Nevertheless, it fits comfortably in the smallest unit of our organism: in our cells. There, DNA serves as a blueprint for synthesising amino acids into proteins - biological molecules that provide metabolism, growth and regeneration in the human body. Without them, not a single one of our cells would work.

To 99 percent of this plan is the same for all people. There are only a few variations that make the difference. For example, you decide whether we are a man or a woman, which personality traits characterize us, or how susceptible we are to certain physical and mental illnesses. But the influence of these genetic differences seems to go far beyond the known, as a study shows.

Variants with influence?

Burkhard Rost from the Technical University of Munich and his colleagues examined the blood of 60, 000 people for their investigation. Surprisingly, they found that the proteins differ more strongly between healthy individuals than expected. Thus, in two unrelated humans, an average of 20, 000 amino acid building blocks vary. In English, these variants are called single amino acid variants, short SAVs.

"So far, many experts believe that most of these variants do not alter anything essential in the function of the proteins, " reports Rost. But is that true? To predict the effects of SAVs, the researchers simulated the influence of these variants on the computer. Because experimental data is available for less than 0.01 percent of SAVs. display

However, the team's computer program used this data to predict the effect on the 99.99 percent of all variants about which nothing is known. "In addition to statistical methods, we use artificial intelligence, especially machine learning and neural networks, " says Rost's colleague Yannick Mahlich.

Amazingly powerful effect

The result surprised the scientists: For millions of SAVs in the proteins of healthy humans, the model calculations predicted strong effects. Variations in the structure of the proteins, which occur more frequently, ie in more than five percent of the population, also have a greater effect on the function of the cell than rare ones Variations that can be observed in less than one percent of the population.

How exactly these effects look like, the researchers can not read the results. For example, the variations could affect how well we can smell, cause altered metabolism, or lead to immunity to pathogens. Also, they could determine how an individual responds to environmental influences or medication.

Impulse for personalized medicine

"Probably none of these effects are recognizable for us in everyday life, " says Rost. "However, some may become relevant under certain circumstances, such as when we first take a particular drug or are exposed to a certain influence. The study of the influence of variations in protein production and function has just begun.",

The new findings are an important impulse for a new, personalized medicine: "Today, it is already possible to deduce the function of individual proteins from DNA. In the future, it will also be possible to derive from this information which nutrition and which medical active ingredients are best for the individual. "(Scientific Reports, 2017; doi: 10.1038 / s41598-017-01054- 2)

(Technical University Munich, 19.06.2017 - DAL)