Cells that are exposed to environmental stress sometimes choose a radical solution, changing the number of copies of their chromosomes - a fast and efficient evolutionary mechanism, but carries a "price tag" of damage to the cell.
People under stressful conditions tend to react to extremes, and sometimes even pay a high price for it, but over time they may find more "balanced" solutions. Even cells that are exposed to environmental stress sometimes choose a radical solution, changing the number of copies of their chromosomes - a fast and efficient evolutionary mechanism, but carries a "price tag" of damage to the cell. Research in yeast cells, conducted recently at the Weizmann Institute of Science, reveals that such extreme coping with environmental challenges is a transient reaction. Over time, the yeast cells adopt more precise solutions, which cost less, and are also more effective in the long term.
The evolutionary mechanism of changing the number of chromosomes (a condition known as "aneuploidy") is widely known and studied. Chromosome duplications, for example, are the result of errors that occur during cell division, but sometimes this error gives the cell an evolutionary advantage, increasing its resistance and survival in certain environmental conditions. In such cases, the cell will keep the extra chromosome and pass it on to the offspring. The duplication is a fast and efficient mechanism - it simultaneously increases the expression of most of the genes found on the extra chromosome, including genes that help the cell deal with stress. However, it comes at a heavy price: cell development is slower because of the "waste" of energy, and in addition, because of excess amounts of genes, the production of proteins in the cell goes wrong and goes out of balance. Multicellular creatures, for example, find it very difficult to bear the negative consequences of chromosome duplication: in the developing embryo they will cause a miscarriage, and the duplication of chromosome 21 in humans will cause Down syndrome. In addition, about 90% of cancerous tumors are characterized by an abnormal number of chromosomes.
Is a change in the number of chromosomes a "Dr. Jekyll" that helps cells, or is it a "Mr. Hyde," harmful and destructive? This question, dubbed the "Aneuploidy Paradox," is at the center of a long-standing scientific controversy.
In order to reproduce the phenomenon of chromosome doubling and to understand it better, the team of scientists, which included Prof. Tzachi Flafel from the Department of Molecular Genetics, and his group members Avihou Yona and Dr. Orna Dahan, created an evolutionary process in the laboratory: for over a year they grew baker's yeast, and followed them Over the course of thousands of generations, a year of experimentation may seem like a very long period of time, but remember that scientists are simulating processes Evolutionary experiments that last, in fact, millions of years. "Evolution in the laboratory" experiments allow not only to shorten the period of time, but provide a controlled environment, without external interference. In addition, while nature allows us to observe only the final result of the evolutionary process, the experiment allows us to closely monitor its development. The yeast was exposed to stressful conditions - heat or a high degree of acidity - which acted as a selection factor: cells that adapted themselves optimally to the conditions, Survive better Every few generations the genome of the cells is examined to try to find the genetic mechanisms that improve survival under stress conditions.
The scientists discovered that when the yeast grows in extreme heat, their resistance and growth speed improve over the generations. The genome test revealed the presence of an extra copy of one of the chromosomes. Growth under high acidity conditions led to the duplication of another chromosome. The scientists concluded that the doubling of the chromosomes is responsible for the yeast's improved ability to cope with the extreme conditions. To prove this, the scientists artificially inserted the extra chromosome into yeast that had not been exposed to the stress conditions. When exposed to high temperature, these yeasts showed resistance similar to those that duplicated their chromosomes naturally.
Unlike other studies, which were satisfied with the detection of the doubling and stopped the experiment after it, the scientists continued to patiently monitor the yeast cells for an additional period. This is how they discovered a surprising phenomenon: over time, the excess chromosome disappeared, and in its place, other, more specific solutions were established, which cost less - but require a longer period of time. These solutions are not based on the doubling of chromosomes, yet the expression of the genes whose role is to deal with stressful situations is kept high - as if the extra chromosome still exists. "In the case of a strong and sudden strain, the cell chooses an effective, quick, and non-optimal solution, because it pays for it to pay the price," says Prof. Pepper. "When there is time to adapt, this solution is replaced by more accurate solutions."
To test this conclusion in another way, the scientists did a "gradual evolution" experiment, in which, instead of growing the yeast under constant extreme stress conditions, they gradually "worsened" the conditions. In this case, chromosome duplications did not occur, probably because the gradual change does not require a quick and extreme solution, but allows the yeast to gradually adapt to the new conditions. "Different evolutionary regimes lead to different types of solutions," says Prof. Pepper. It turns out that the efficiency of these solutions is also different: in the graded evolution experiment, the cells adapted better to the environmental conditions, and the adaptation mechanisms were maintained for a longer period of time. The research findings were published in the journal PNAS.
The scientists believe that their findings may also be relevant for cancer cells, and in particular for how cancer cells get rid of cancer-suppressing genes, so that they can reproduce and thrive without interruption. If there is a mutation in one of the chromosomes, which affects the cancer suppressor gene, the cell may duplicate the mutant chromosome, and then omit the normal one, thus getting rid of the "brakes" that limit it. In addition, understanding how environmental challenges, extreme or gradual, affect the cell's ability to cope, may contribute to the planning of an effective chemotherapy treatment, which will, if possible, reduce the ability of the cancer cell to develop resistance mechanisms.
