21st Century Guidebook to Fungi, SECOND EDITION, by David Moore, Geoffrey D. Robson and Anthony P. J. Trinci

Table of Contents

1. Chapter 4: Hyphal cell biology and growth on solid substrates
2. Chapter 5: Fungal cell biology
   1. Mechanisms of mycelial growth
   2. The fungus as a model eukaryote
   3. The essentials of cell structure
   4. Subcellular components of eukaryotic cells
   5. The nucleus
   6. The nucleolus and nuclear import and export
   7. Nuclear genetics
   8. Mitotic nuclear division
   9. Meiotic nuclear division
   10. mRNA translation and protein sorting
   11. The endomembrane systems
   12. Cytoskeletal systems
   13. Molecular motors
   14. Plasma membrane and signalling pathways
   15. Fungal cell wall
   16. Cell biology of the hyphal apex
   17. Hyphal fusions and mycelial interconnections
   18. Cytokinesis and septation
   19. Yeast-mycelial dimorphism
   20. Chapter 5 References and further reading about the cell cycle
   21. Buy a PDF of Chapter 5
3. Chapter 6: Structure and synthesis of fungal cell walls

5.2 The fungus as a model eukaryote

The cell we are describing is the generalised cell of a eukaryote. In most textbooks when this is attempted it is usually the animal cell that takes centre stage (e.g. the classic cell biology text, Alberts et al., 2014); plant cells might be described occasionally, when there’s a need to deal with photosynthesis, and yeasts may get a mention as the source of some of the molecular detail. There’s nothing wrong with that (although animal cells do not have the cell wall that’s so important to the other eukaryotic kingdoms, this feature being lost in the distant past by the single-celled opisthokonts that gave rise to Kingdom Animalia), but it does downplay the enormous contribution that fungi have made to development of our knowledge of eukaryotic cell biology. As well, perhaps, as downplaying the enormous contribution that the fungal life style has made to the evolution of eukaryotic cell biology.

Although several unicellular eukaryotes have been used as models in cell and molecular biology (Simon & Plattner, 2014), the fact is that most of what we know about the biology of the cell of higher organisms derives from work with yeasts. Most biologists would recognise the contribution made by yeast research to molecular biology in the 1990s. The first complete sequence analysis of any eukaryote chromosome was that of the entire DNA sequence of Saccharomyces cerevisiae chromosome III, published in 1992 by a large international team led by Steve Oliver. This was followed in 1996 by the sequencing of the whole of the genome of S. cerevisiae, which was the first eukaryote genome to be sequenced (the 13-year human genome project, which got all the headlines, was completed in 2003).

Some biologists will know that the Nobel Prize for Physiology or Medicine in 2001 was awarded to three scientists '...for their discoveries of key regulators of the cell cycle', and two of them worked with yeasts (Leland Hartwell worked with Saccharomyces cerevisiae, and Paul Nurse with Schizosaccharomyces pombe; the third Laureate was Tim Hunt who worked with sea urchin eggs) (see https://www.nobelprize.org/nobel_prizes/medicine/laureates/2001/). So, the whole of genomics and cell cycle biology rests on foundations built with yeasts. But the crucial contribution goes much further back than the end of the 20th century; it goes back to the mid-19th century. The history of yeast in biology effectively starts with Louis Pasteur who connected yeast to fermentation in 1857 and demonstrated that the growth of microorganisms in nutrient broths is not due to spontaneous generation.

The word ‘yeast’ is a general term for any growth that appears in a fermenting liquid. In its origins, the word means frothy or foamy so it’s descriptive of the fermentation process but has become associated with the agent of fermentation. When grape juice is collected it ferments quite naturally, and the growth that occurs and eventually forms sediment is ‘yeast’. Making alcoholic drinks is such a simple process that all societies, even the most primitive, have one or more fermentations that they include in their rituals. There are some ancient Egyptian murals and tomb ornaments depicting both baking and wine making. From the biological point of view it is remarkable that the one organism responsible for most fermentations is the yeast now called Saccharomyces cerevisiae, but known as Brewer’s yeast in one trade, and Baker’s yeast in the other (though we will call it ‘budding yeast’). Remember that yeasts (as well as filamentous fungi and other microbes) are present on the surfaces of grapes, fruits and seeds in nature so there was no need to add them and food preparation processes like these were carried out with no knowledge of the importance of microbes in the fermentation processes involved. Saccharomyces cerevisiae comes to the fore so often because its metabolic controls allow it to produce alcohol even in the presence of oxygen, a theme to which we will return in Chapter 17 (CLICK HERE to view now).

At the end of the nineteenth century industrialisation created the need to guarantee and improve production and product quality, and this prompted brewers and wine makers to sponsor research into the nature of fermentation. This naturally came to focus on the single celled microorganisms we call yeast. Studies of yeast metabolism essentially founded the sciences of biochemistry and enzymology. Purification of cultures (necessary for a uniform product) and a drive to improve cultures (to increase the efficiency of fermentation or develop new products) was enhanced by the parallel development of the science of genetics at the beginning of the twentieth century. Pasteur was employed by the wine growers to improve the wine fermentation. From his experiments Pasteur concluded: 'I am of the opinion that alcoholic fermentation never occurs without simultaneous organisation, development and multiplication of globules (cells)...' (Pasteur, 1860, 1879). And those cells, of course, were fungal (yeast) cells.

Pasteur died in 1895, before the first Nobel Prizes were awarded (in 1901; visit https://www.nobelprize.org/alfred_nobel/ (needs Internet connection)), but the winner of the 1907 Nobel Prize in chemistry was Eduard Buchner ('…for his biochemical researches and his discovery of cell-free fermentation…' CLICK HERE to visit the page), who determined that fermentation was actually caused by a yeast secretion that he termed zymase; we now call such things enzymes. Buchner’s experiment for which he won the Nobel Prize consisted of producing a cell free extract of yeast cells and showing that this ‘press juice’ could ferment sugar. Here we have the beginnings of our understandings of cell biochemistry and metabolism, and we can chart the progress of basic biological knowledge through subsequent Nobel prizes (visit https://nobelprize.org/nobel_prizes/).

The Prize in Chemistry 1929 went to Arthur Harden (who worked on the involvement of phosphates in respiration of yeast) and Hans von Euler-Chelpin (who worked on enzymology and oxidative respiration of yeast) '…for their investigations on the fermentation of sugar and fermentative enzymes…' CLICK HERE to visit the page. Hans von Euler-Chelpin’s Nobel Lecture included the paragraph:

'Within the living organism, the majority of reactions are brought about by special substances already active in minimum quantities, such substances being known as enzymes or ferments. Every group of substances, and in fact practically every substance, requires its specific enzyme for its reaction. Only a few enzyme types were known in the early days, such as pepsin in the gastric juice, which splits proteins, or amylase in saliva and in malt, which converts starch into sugar, but in more recent times the number of enzymes whose existence has been proved or substantiated, has risen to over 100' (https://www.nobelprize.org/uploads/2018/06/euler-chelpin-lecture.pdf). This lecture was delivered in May 1930.

Over the next quarter of a century the great network of metabolism was established, and the genetic segregation side of the story was developed, too. Mendel’s work on garden peas was rediscovered and republished in 1900 and inspired many experimenters to replicate and confirm his discovery of gene segregation. At about the same time it was becoming evident that vegetative cells of S. cerevisiae are usually diploid, produced by ‘copulation’ of two haploid spores. In the early 1930s the basic facts of the yeast life cycle were established, in particular that diploid nuclei underwent meiosis (the reduction division) during spore formation to produce four haploid ascospores. With the life cycle so clearly established the way was open for breeding experiments. By the 1940s it was possible for Carl Lindegren to write:

‘...Thirteen asci were analysed from a heterozygous hybrid made by mating a galactose fermenter by a nonfermenter; two spores in each of these asci carried the dominant gene controlling fermentation of galactose, and two carried the recessive allele. A backcross of fermenter [offspring] to the fermenter parent produced thirteen asci; all four spores in each of these asci carried the fermenting gene. A backcross of the nonfermenter to the nonfermenting parent produced seven asci, each of which contained four nonfermenting spores. A heterozygous zygote was produced by backcrossing a nonfermenter [offspring] to the fermenting parent; six asci were analysed and each contained two nonfermenting spores. This analysis shows quite convincingly that the genes controlling fermentation of galactose behave in a regular Mendelian manner.’ (Lindegren, 1949).

So, within a few decades of the rediscovery of Mendel’s experiments with peas, those experiments had been repeated with yeast and had demonstrated that yeast genes operated to the same set of rules as did pea genes. In other laboratories the first metabolic pathways were constructed using nutritionally deficient mutants of the filamentous ascomycete fungus Neurospora, and the bacteria Escherichia and Salmonella.

In 1958 the Nobel Prize in Physiology or Medicine was awarded to George Beadle, Edward Tatum (both of whom worked with Neurospora) '…for their discovery that genes act by regulating definite chemical events…' and Joshua Lederberg '…for his discoveries concerning genetic recombination and the organisation of the genetic material of bacteria…' CLICK HERE to visit the page.

During the first half of the twentieth century, then, yeasts and related filamentous fungi (Davis, 2000; Gladieux et al., 2020; Machida & Gomi, 2010; Samson & Varga, 2008) provided the foundation of knowledge of cell biochemistry, metabolism and its genetic control, and then, as we have mentioned, the same conceptual approach (isolating mutants defective in steps of a pathway to study that pathway) was applied to the cell cycle by Leland Hartwell and Paul Nurse (CLICK HERE to visit the page).

The distribution of prizes continues: the Nobel Prize in Chemistry in 2006 went to Roger D. Kornberg ‘…for his studies of the molecular basis of eukaryotic transcription…’ (https://www.nobelprize.org/nobel_prizes/chemistry/laureates/2006/). The Prize in Physiology or Medicine 2009 was awarded jointly to Elizabeth H. Blackburn, Carol W. Greider and Jack W. Szostak ‘…for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase..’ (https://www.nobelprize.org/nobel_prizes/medicine/laureates/2009/); and the Physiology or Medicine Nobel Prize 2013 was awarded jointly to James E. Rothman, Randy W. Schekman and Thomas C. Südhof ‘…for their discoveries of machinery regulating vesicle traffic, a major transport system in our cells…’ (https://www.nobelprize.org/nobel_prizes/medicine/laureates/2013/). All of these prize-winning discoveries were supported by research on yeasts.

What we are planning to do next is introduce you to the working eukaryotic cell. There are a number of ways we could approach this, and we have chosen to focus on the typical fungal cell (and to headline, when needed, how this cell type differs from animal and plant cells), starting our description from the DNA level, towards the end we will concentrate on the features that contribute most to apical extension of the filamentous hypha characterising the fungal lifestyle as already described.

Updated January, 2020