Science: Microbe of the Month - Yeast and its clinging daughters / Bernard Dixon looks at a well-known organism that remains full of surprises

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The Independent Online
THE European Commission was understandably cock-a-hoop recently when it announced that EC-sponsored research had revealed the entire sequence of 315,000 chemical units comprising one of the chromosomes of the yeast Saccharomyces cerevisiae. It was a remarkable accomplishment by collaborating scientists in 35 laboratories in 17 different countries.

But S. cerevisiae had a surprise in hand. For centuries, brewers and bakers have used this yeast to make beer and bread. For decades, scientists have scrutinised it so intensively that we now understand its biochemistry and genetics as thoroughly as those of any other living organism. Yet, at the moment when the chromosome sequencing was being completed, S. cerevisiae turned up in Cambridge, Massachusetts, in a guise never previously described.

Growing as a filamentous 'mycelium' rather than the familiar oval-shaped cells, S. cerevisiae has surprised yeast experts, who felt they knew all there was to know about the form of their favourite microbe. The change was not the result of a sudden mutation but seems to be an aspect of the yeast's normal life in nature .

From a human standpoint, the shift from single cells towards a thread-like lifestyle may seem trivial. Biologically, it is highly significant because it indicates the existence of genetic 'switch' between the two life forms. Although researchers have found switches that trigger a transformation from cellular to filamentous growth in many related moulds, they long ago concluded that S. cerevisiae had lost this capacity through evolution. The new finding suggests that the yeast could become a useful laboratory model for investigating diseases (vaginal thrush, for example) caused by other yeasts that have a filamentous phase.

Our relationship with S. cerevisiae goes back at least as far as the brewing that took place in Mesopotamia some 6,000 years ago. Scientific studies began essentially with Louis Pasteur towards the end of the last century, and matured over subsequent decades as biochemists used yeast to work out the intermediary steps that cells use to break down food materials. One of the earliest was that through which yeast gains energy by converting sugar into alcohol and carbon dioxide - benefiting the brewer and baker respectively.

More recently, geneticists have located the genes responsible for many of these chemical processes. Indeed, the genetics of S. cerevisiae are now so well understood that it has become a favoured organism for genetic engineers to clone genes taken from other cells. One application is to store large fragments of DNA as 'yeast artificial chromosomes'. Under the EC project, the entire sequence of chemical units in the genes carried by all 16 chromosomes of S. cerevisiae is due to be determined before the end of the century.

No doubt one or more of those genes will be found to determine the switch to filamentous growth reported by Gerald Fink and colleagues at the Whitehead Institute and Massachusetts Institute of Technology. What makes their discovery remarkable is that it stemmed not from highly sophisticated science but from a simple experiment that any first-year student might have performed. Mr Fink decided to investigate the growth of S. cerevisiae - not under typical laboratory conditions, in which microbes are amply supplied with all essential nutrients, but in the state of semi-starvation that often occurs in nature. What would happen if the yeast lacked one or more of these nutrients?

The breakthrough came when they studied nitrogen. Deprived of this vital element, the yeast failed to grow. But when placed in a medium in which nitrogen was merely reduced below its optimal level, the organism began to proliferate as filaments. This occurred because daughter cells, which normally bud off from their parents to form independent cells, remained attached - producing further daughters in turn, and thus generating chains of connected cells.

One consequence of the altered lifestyle is that the filaments, unlike 'normal' individual cells, can penetrate into the nutrient agar in which they are growing. Mr Fink suspects that in nature this shift in behaviour is a foraging manoeuvre. Whereas single cells cannot move, except passively, the filamentous yeast can spread itself in the hope of reaching new sources of nutrients.

This, then, is the discovery that I and countless other yeast researchers never made. As a young PhD student some 30 years ago, I spent many hours growing S. cerevisiae and even starving it of an essential nutrient. But in my case this was the B vitamin biotin, whose role in enzyme synthesis I was trying to rumble. Although my electron micrographs occasionally showed cells that had failed to separate from their parents, I never encountered the filamentous strings described by Gerald Fink. And I never got around to studying nitrogen deficiency. Such is life.