Genotype and phenotype

Svetlana Borinskaya: "The warranty period of a person is 40 years"

The editor-in-chief of PostNauka Andrey Babitsky talked with biologist Svetlana Borinskaya about what is determined by genes in a person's life, whether it is possible to influence it and what role the environment plays here.

– Can there be headlines in the spirit of: "Researchers have found a gene that determines the ability to memorize letters" at least theoretically be true in your eyes?

– Yes and no. Genes that affect a trait are found when comparing groups, one of which has the desired trait, and the other does not. For example, one group knows how to tie shoelaces, the other does not. In such comparisons, it is indeed possible to find gene variants that affect the trait being studied. But it is impossible for an individual to predict that once he has this gene, then there will certainly be a sign associated with it when comparing groups. A person has more than 20 thousand genes. There may be a dozen more among them that affect the same trait, and this influence can negate the action of a single gene.

– And most of the genes we find are not even Mendelian?

– Mendelian signs are called. They are arranged like this: one gene is one trait. In humans, these are, as a rule, the genes of mendelian diseases, hereditary. In other words, if there is a mutation in some gene, then there must be a disease. But even here, not everything is so simple. About a dozen people in the world have been found who have mutations associated with hereditary diseases, but there are no diseases themselves. It is unclear why this is happening. Maybe some other gene compensates for this defect. Of course, the frequency of exceptions is extremely low: for hundreds of thousands of genomes studied, several people were found. However, this is a vivid illustration of the fact that the presence of a mutation is not a verdict.

From my point of view, hereditary diseases are those for which we could not find optimal environmental conditions for a person. For some diseases, this is possible. For example, phenylketonuria is a metabolic disorder in which one of the enzymes does not work, and phenylpyruvic acid, which it must break down, accumulates and poisons the child's brain. But if you remove from the child's diet those foods that lead to the formation of this phenylpyruvic acid, then the child can grow up practically healthy.

– Accordingly, it is possible to change the environment, or can we try to fight the genetic factor?

– You can try to change the genes. This is called gene therapy. Gene therapy for some diseases is already being carried out, and there are people who have been helped by it. For example, such approaches are being developed for Duchenne myodystrophy. This is a mutation in a gene that causes a child to die in adolescence because his muscles stop working. In several cases, children survived with the introduction of certain genes.

Genes do not determine everything, although, as with any other disease, there are few examples when it is genes that play a decisive role. For example, there are genes in which mutations lead to premature Alzheimer's disease – senile dementia. But this is about 5% of all cases. Or, say, mutations in the BRCA gene lead to an 80 percent chance that a woman will develop breast cancer, and most likely at a fairly young age. However, this happens infrequently.

– Does any disease imply genetic variability?

– In general, the very fact of our existence is due to the fact that we have genes. They program, although not fully, the development of the organism and its reactions to the world around it – both biochemical and psychological. For example, if a person stumbled and broke his leg, then the influence of genes on his attentiveness or fragility of bones is not excluded.

In order to explain why the cells of our body are different, although the set of genes in them is the same, I like to use a comparison with a piano keyboard. The keyboard is the same, but you can play different chords on it. It's the same with the genome, the set of genes is the same in each cell, but different sets of genes work in different cells – we can say that different chords sound in them. Genes turn on and off, and as a result, cells change, perform certain functions. When we do something – eat, get scared, rejoice, exercise, think – genes can react to it.

The hypothesis about the influence of a gene is confirmed when in several independent studies the same gene turns out to be associated with a certain trait, however, there are also subtleties. For example, the influence of behavior.

For example, the enzyme alcohol dehydrogenase breaks down alcohol in the liver and turns it into the toxin acetaldehyde, which is then broken down by another enzyme. The speed of these enzymes is set genetically. If a person has a variant of the gene that determines the rapid conversion of alcohol into a toxin, then he has more unpleasant sensations after drinking. We conducted a study on Russian men and found that they, as well as men in other countries, carriers of the gene variant that determines the rapid conversion of alcohol into acetaldehyde, consume 20% less alcohol on average.

Upon closer examination, it turns out that people with higher education who have this variant of the gene drink 40% less. Men without education, regardless of which gene variant they have, consume on average equally large amounts of alcohol, despite feeling unwell. Perhaps this is due to the fact that their stress levels are higher. In all countries, the social well-being of people with higher education is higher, their stress levels are lower and their life expectancy is longer. Of course, there may be alcoholics among educated people, but there are more of them in the group without higher education.

– What is the reason for the inability of a person to synthesize vitamin C and why do we not consider it a disease?

– Vitamin C is synthesized in the body of many mammals. The ancestors of primates lost the ability to synthesize vitamin C when vitamin C was in excess in their food. They ate green branches and received the necessary amount of vitamin with them, there was no need to synthesize it themselves. If the selection does not follow the sign, it can easily be lost. This is what happened: mutations damaged the gene necessary for the synthesis of vitamin C. But when people switched to agriculture, they could not always get vitamin from food.

We know that a person had this ability before because there are pseudogenes in the genome – these are sections of DNA that used to be full-fledged genes, but they have accumulated a lot of mutations. As soon as a gene is switched off, mutations can accumulate in it as much as they like, because this will no longer affect its functioning. If mutations do not affect important features, then they are preserved, and otherwise they are not transmitted. In order for the gene to work again, certain mutations or gene transplants from other mammals are required. However, it is much easier to get vitamin C from food.

– What fundamentally new things have we learned about genes in the last two or three years?

– We learned that some signs are not directly related to the DNA sequence, but to the chemical labels that are present on this DNA. Each gene has a switch – promoter. If it is chemically modified (to hang methyl groups), the gene will slow down or stop its work. This is called "epigenetic regulation". It helps to predict many signs noticeably more accurately than just by genes. For example, smoking can be fairly accurately determined by the level of methylation – a person has marks in certain places of DNA. It will not be possible to find out this by genes just as effectively.

We know that environmental exposure changes how genes work. Exercise and proper nutrition have a positive effect on the functioning of the body, including through changing the work of certain genes.

And that's why we can improve our health by doing exercises, eating right. Recent scientific studies show that this gives an increase of ten or more years of life. However, this will not provide a person with super longevity. For hundreds of millennia of human history, the average life expectancy was somewhere around 30-40 years. Therefore, in a sense, the warranty period of a person is 40 years. It is important to understand that, from the biologist's point of view, immortal individuals are harmful, since there will be no evolution, and if something significant changes in the external environment, the species will die out.

There is a wonderful saying by Jonathan Swift: "Everyone wants to live long, but no one wants to be old." In the meantime, by the age of 80, many people have various health disorders, including senile dementia. So far we can slow it down, but not prevent it. Physical and intellectual activity, a healthy lifestyle make the process not so fast. But who would want to lead such a life if the Earth is filled with half-crazy elderly people? It is necessary to preserve their health. That is, we are not talking about life expectancy, but about the duration of a healthy life.

About the author:
Svetlana Borinskaya – Doctor of Biological Sciences, Head of the Genome Analysis Laboratory of the N. I. Vavilov Institute of General Genetics of the Russian Academy of Sciences.

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