## When we want to understand the functioning of a eukaryotic cell, the model organism must be an eukaryote

How to choose from the enormous number of species of eukaryotic organisms? Figure 20.1 illustrates the great diversity of eukaryotes, most of which are single-celled organisms that for the purposes of this text (though incorrectly in terms of modern taxonomy) can be called protozoa. When we are interested in the functioning of human cells, the first step is to look for a type of organism that meets the requirements for a model organism but that is also closely related to humans. On our simplified version of the phylogenetic tree, we see that this requirement could be met by a representative of the group of fungi. Not the macroscopic mushrooms that we collect in forests or put on our pizzas, but microscopic species that can exist in a single-celled state. Fungi called yeast fulfil this requirement.

Yeast are eukaryotic microorganisms that can ferment various carbon sources, for example the sugar from freshly crushed grapes (so-called grape must). In this case, it is a yeast of the species Saccharomyces cerevisiae, which has accompanied mankind for the past several thousand years as an assistant in the production of wine, beer, and baked goods. Louis Pasteur (1822 – 1895) proved that S. cerevisiae is an agent that converts sugar into alcohol, and since then this yeast has not only been the workhorse of classical biotechnology but has become an honorary member of the imaginary Pantheon of model organisms.

Although the cells of S. cerevisiae are relatively small (3-5 mm compared to the approx. 100 mm diameter of a typical human body cell), their structure is very similar to mammalian cells (Figure 20.4). A yeast cell is specific in some respects, for example, it has a cell wall, it divides by budding (that's why S. cerevisiae is sometimes referred to as budding yeast). However, yeast cells also contain organelles characteristic of eukaryotic organisms, its genome is separated from the rest of the cell by a membrane that encloses the cell nucleus, and its cell cycle is regulated in an analogous manner to mammalian cells. This was proved by the American biologist Leland Hartwell, who in the 1970s prepared a collection of cell division cycle (cdc) mutant strains of S. cerevisiae that were unable to pass through one of the phases of the cell cycle. A few years later, the British geneticist Paul Nurse identified cdc mutants in the cell cycle in another yeast species Schizosaccharomyces pombe (or simply fission yeasts) and at that time attempted a very brave experiment to answer the question: Would it be possible to replace a faulty yeast gene with a human gene, which would restore the yeast cells the ability to divide? Together with his student Melanie Lee, they discovered that there really is a human gene that can fully function in yeast cells. This result underscored the evolutionary relatedness of such seemingly dissimilar organisms as fungi and mammals and confirmed that the study of biological phenomena in simple organisms enables the formulation of models valid for human biology as well.

It turns out that the regulation of the cell cycle of yeast and mammalian cells is fundamentally similar, and its disturbances have the same consequences: either loss of the ability of cells to divide, or division even in conditions where it should be stopped. This is, for example, the case of tumour cells that are not able to correctly evaluate the signals that indicate to the cell that it should stop the cell cycle. Such a signal can be, for example, DNA damage, which a normal cell evaluates by stopping the cell cycle, repairing the damage, and only then restarting the cell division. A tumour cell that has lost this ability due to a mutation in the genes controlling the cell cycle will continue to divide even if the DNA damage is not repaired, increasing the likelihood of further mutations that promote uncontrolled division. You have read more about this in Chapter 9 – when cells go crazy.

The impressive list of crucial discoveries stemming from yeast research covers a wide range of phenomena including protein secretion, biogenesis of organelles, autophagy, bioenergetics, genome stability, chromosome segregation, and many, many more. As in case of the mechanisms of cell cycle regulation, the results shed more light on the cellular processes occurring in normal human cells including specialised cell types such as pancreatic beta-cells or neurons as well as in cells exhibiting pathologies causing various human diseases.

In addition to these fundamental discoveries, research on yeasts contributed to the development of new technologies, which subsequently found application in the research of more complex organisms. For example, the first eukaryotic organism in which the complete order (sequence) of nucleotides in all chromosomes was determined in 1996 was the yeast S. cerevisiae, which opened the way for the sequencing of the human genome at the beginning of this millennium.