The 20th anniversary of the Saccharomyces cerevisiae yeast genome
This year we celebrate the 20th anniversary of the complete sequencing of the Saccharomyces cerevisiae yeast genome. It was on 24 April 1996 that this collaborative effort, which brought together 600 scientists, reached its fruition in a press conference given by Professor André Goffeau, who initiated and coordinated the project (Goffeau et al., 1996). Yeast will forever be the first eukaryotic organism to have a fully-sequenced genome.
The 20th anniversary of this major event presents us with an opportunity to reflect on the legacy of this important milestone in research carried out on Saccharomyces cerevisiae, which is both extremely useful in many areas of our everyday lives and serves as a model for eukaryotic cells.
So, what has the legacy of the Saccharomyces cerevisiae genome published in 1996 been? More specifically, we are talking about the S288C S. cerevisiae strain, the variant sequenced at the time. Notable aspects of this legacy include numerous “genome-wide” approaches, some of which are discussed below.
The genome firstly paved the way for a second collective effort started in 1998 and finalised in 2002 (Giaever et al., 2002). The research community got to work, this time to create collections of S. cerevisiae yeast from several thousand individual strains, each deficient in a certain gene. To do this, each of the yeast’s 6,000 genes had to be deactivated. This had to be done in particular because many (of which there are still some) had unknown functions. Once a gene is deactivated, it is easier to establish its function by noting the effects of its absence. Several collections were created: an a-sign haploid collection, an alpha sign collection, a heterozygous diploid collection, and a homozygous diploid collection.
The collections’ interest
These collections have several uses, such as the Synthetic Genetic Array Analysis technique developed by Charlie Boone — the absence of certain genes can have no apparent effect, but the absence of two genes at a time can have an effect. This technique can be used to establish a map of the links that exist between genes (Tong et al., 2001).
However, before this, the S. cerevisiae could be examined to demonstrate an important event in its history. Ken Wolfe demonstrated that the genome has a certain level of duplication (Wolfe & Shields, 1997).
It is partly duplicated and conserves certain traces of fossils from the event that gave yeast the ability to provide the new genes formed with new functions.
There are many other yeasts aside from Saccharomyces cerevisiae. Thanks to the formidable developments in sequencing techniques, a consortium of French laboratories then tackled the task of characterising many other types of yeast. This was the “Génolevures” project led by Bernard Dujon, (Dujon et al., 2004). The study was able to more accurately pinpoint when the genome duplication discussed above occurred. The study also introduced “s” yeasts into the genomic era, and to all of the approaches and techniques related to this field, as was S. cerevisiae some years previously.
The genome also granted access to transcriptome, a collection of RNAs produced during gene creation. Genome information results in the creation of “DNA chips” that individually quantify each of the RNAs encoded by the genes. This paved the way for comprehensive studies that resulted in a better understanding of how yeast responds to its environment (thermal shock, various deficiencies, etc.), and other stimuli/mutations, by identifying the genes whose activity is affected by these external factors (see Gasch et al., 2000, for example).
But let’s go back to yeast in 1996. As a reminder, it involved a particular strain called “S288C”. It was a bit like sequencing the human genome, but only Joe Bloggs’.Researchers at that time were looking into characterising the genes or portions of a genome that “explain” the differences between the “individuals” in Saccharomyces cerevisiae, described as “strains”. The 1996 genome turned out to be a precious starting point for working towards identifying genes and the portions of a genome by QTL mapping.
From the overall finding that two different strains tolerate thermal shock differently, it was possible to investigate the genetic origins of this difference at the nucleotide level (Steinmetz et al., 2002).
Knowledge of the yeast genome also increased as sequencing techniques became more powerful. It was then possible to sequence dozens of strains of the same Saccharomyces cervesiae yeast to establish their genetic relationship and see the influence their geographical area of origin or use had on their genome (Liti et al., 2009).
The genomes of 1011 strains
A project aiming to characterise the genome of 1,011 different strains of S. cerevisiae is coming to an end at the time of reading (http://1002genomes.u-strasbg.fr/index.html). In 20 years we have gone from the genome of the S. cerevisiae yeast to the genome of yeasts, and then to the genomes of 1,011 strains of the S. cerevisiae yeast.
Beyond the studies mentioned above, others worked to make the genome and related information available to a larger audience. This is why the Saccharomyces cerevisiae Genome Database at Stanford University was set up in 1998 (Cherry et al., 1998). This was a formidable tool that any researcher with an Internet connection could then use to research the genome and learn about all kinds of genes in just a few clicks.
This is a non-exhaustive representation of the genome’s journey since 1996, which began with the first genome. This was a painstaking task given the technology available at the time, and was an invaluable coup for yeast researchers to speed up their research into the organism, used by humans both as a tool and a model. It was tempting to think that the job was done in 1996 when a comprehensive understanding of the genome emerged. This clearly wasn’t the case. While the area of yeast has been studied for a long time by a community of gifted, dynamic researchers, there are still many things to be learnt.