Chromosome mutations in yeast cells caused by stress
When we consider the concept of evolution, we think of genetic changes in a population over time – perhaps over hundreds or thousands of years. However, some organisms appear to have the ability to genetically evolve in just a few days by inducing chromosome mutations in response to stressful conditions. This phenomenon was studied by a team from the Stowers Institute for Medical Research in 2011. By examining the effects of several stressors, including heat and extreme chemical concentrations, they found that chromosomal variations and consequent drug resistance is the result of the action of heat-shock protein 90 (Hsp90).
In the experiment, yeast cells were submitted to high and low concentrations of a variety of chemicals for 12 to 14 hours. Then, the number of colonies of yeast cells that had an uneven number of chromosomes was compared with the number of colonies with the normal number of chromosomes. Many different stress factors increased chromosomal instability in yeast cells. Most significantly, the result of exposing yeast cells to the drug radicicol, even at a low concentration, was a chromosome loss rate about 300 times higher than the control in stress-free conditions. Exposure to a temperature of 50.9°C produced a similar result.
Graph displaying effects of stress conditions on frequency of colonies that are missing chromosomes
Images displaying effects of stress conditions; red colonies have chromosomal abnormalities
The reason for this surprising result is that radicicol binds to the Hsp90 molecule and disrupts its performance and heat also inhibits the protein. Hsp90 aids the correct duplication of chromosomes during cell division so that the daughter cells contain the same number of chromosomes as the parent cell.When Hsp90 is inhibited, replicated cells are more likely to demonstrate aneuploidy, meaning that they are missing or have an extra copy of a single chromosome.
The genetically diverse colonies of yeast produced by radicicol treatment were then exposed to several different drugs and their performance compared to control colonies. The results showed that the survival rates of the radicicol-treated colonies were much higher against all three drugs.
Images displaying comparison of control yeast colonies and radicicol-treated yeast colonies after exposure to drugs
So how does genetic diversity give a population such an advantage when it comes to survival? Genes within chromosomes determine which proteins are produced in a cell. The number of copies of a gene present in a cell may influence the expression of the gene and thus the final physical characteristics of the organism.For example, four of the yeast colonies that survived exposure to fluconazole demonstrated aneuploidy by containing an extra copy of chromosome 8, and by consequence, an extra copy of the ERG11 gene.This gene helps make organisms more resistant to fluconazole, which normally causes damage to the cell wall of fungal cells.
While the study helps explain one of the mechanisms that make some strains of yeast cells drug resistant, it could be useful in predicting the response of cancer cells to certain treatment. The researchers highlighted similarities between yeast and cancer cells, which often have unusual numbers of chromosomes. This is significant because, previously, some drugs were thought to be able to fight cancer by inhibiting Hsp90 and damaging protein production in the cancer cells.However, these drugs may actually produce drug-resistant cancer cells instead of treating cancer.
When we consider the concept of evolution, we think of genetic changes in a population over time – perhaps over hundreds or thousands of years. However, some organisms appear to have the ability to genetically evolve in just a few days by inducing chromosome mutations in response to stressful conditions. This phenomenon was studied by a team from the Stowers Institute for Medical Research in 2011. By examining the effects of several stressors, including heat and extreme chemical concentrations, they found that chromosomal variations and consequent drug resistance is the result of the action of heat-shock protein 90 (Hsp90).
In the experiment, yeast cells were submitted to high and low concentrations of a variety of chemicals for 12 to 14 hours. Then, the number of colonies of yeast cells that had an uneven number of chromosomes was compared with the number of colonies with the normal number of chromosomes. Many different stress factors increased chromosomal instability in yeast cells. Most significantly, the result of exposing yeast cells to the drug radicicol, even at a low concentration, was a chromosome loss rate about 300 times higher than the control in stress-free conditions. Exposure to a temperature of 50.9°C produced a similar result.
Graph displaying effects of stress conditions on frequency of colonies that are missing chromosomes
Images displaying effects of stress conditions; red colonies have chromosomal abnormalities
The reason for this surprising result is that radicicol binds to the Hsp90 molecule and disrupts its performance and heat also inhibits the protein. Hsp90 aids the correct duplication of chromosomes during cell division so that the daughter cells contain the same number of chromosomes as the parent cell.When Hsp90 is inhibited, replicated cells are more likely to demonstrate aneuploidy, meaning that they are missing or have an extra copy of a single chromosome.
The genetically diverse colonies of yeast produced by radicicol treatment were then exposed to several different drugs and their performance compared to control colonies. The results showed that the survival rates of the radicicol-treated colonies were much higher against all three drugs.
Images displaying comparison of control yeast colonies and radicicol-treated yeast colonies after exposure to drugs
So how does genetic diversity give a population such an advantage when it comes to survival? Genes within chromosomes determine which proteins are produced in a cell. The number of copies of a gene present in a cell may influence the expression of the gene and thus the final physical characteristics of the organism.For example, four of the yeast colonies that survived exposure to fluconazole demonstrated aneuploidy by containing an extra copy of chromosome 8, and by consequence, an extra copy of the ERG11 gene.This gene helps make organisms more resistant to fluconazole, which normally causes damage to the cell wall of fungal cells.
While the study helps explain one of the mechanisms that make some strains of yeast cells drug resistant, it could be useful in predicting the response of cancer cells to certain treatment. The researchers highlighted similarities between yeast and cancer cells, which often have unusual numbers of chromosomes. This is significant because, previously, some drugs were thought to be able to fight cancer by inhibiting Hsp90 and damaging protein production in the cancer cells.However, these drugs may actually produce drug-resistant cancer cells instead of treating cancer.
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