Scientists at the Francis Crick Institute and the University of Cambridge have grown around 5,000 strains of yeast, each missing a different gene, to find out what role each gene plays. This staggering piece of work led to the discovery that a huge proportion – a third – of the genes are involved in metabolism.
The researchers used the findings to connect the genes to each other in a large map of gene function – attributing roles to around half of the yeast genes for which function was previously unknown.
Metabolism is the name for the biochemical processes that occur inside a cell to maintain life. It includes the breakdown of nutrients to provide energy and produce small molecules such sugars, amino acids, fatty acids and vitamins, as well as the use of this energy to create the proteins and other molecules the cell needs to carry out its functions. Amino acids are the building blocks of proteins – they are joined together in different orders to create the countless different proteins that cells need.
First author of the study Michael Mülleder was responsible for growing the 5,000 yeast strains that lacked one gene each, called ‘deletion strains’. He then used mass spectrometry – an analytical technique that allowed him to determine whether there were any differences in the content of amino acids between each strain of yeast.
Dr Mülleder of the Francis Crick Institute and the University of Cambridge, says: “Amino acids are very crucial components for metabolism, so the cells need to make sure that they are taken up, broken down or made in the right quantities. That’s why we thought that by measuring them in all of the accessible yeast gene-deletion strains, we would reveal the set of mechanisms that control metabolism.”
Dr Markus Ralser, who led the work at the Crick and Cambridge, says: “We found that a third of the missing genes impacted amino acid metabolism, many of them strongly. This is much higher than anyone expected.
“We know of no other biological process that requires as many genes to function. Obviously, metabolism played a fundamental role in shaping the way our biologically systems work. It seems the genome is basically structured around it.
“Amino acids play a crucial role in our diet, are implicated in metabolic diseases such as diabetes, and their imbalance causes several rare clinical conditions. Knowing more about how cells deal with them will eventually improve the way we treat these conditions. Further, it will allow us to refine dietary recommendations, perhaps even to tailor them to individuals based on their genetic information.”
The scientists will now work on improving the technology they used, so that they can address other parts of metabolism, such as those linked to sugars and fatty acids. This will allow them to assign roles to several of the genes that still remain uncharacterised.
Because many yeast genes have human counterparts that also have unknown functions, identifying yeast gene functions can help us understand what human genes do. This can be the first step towards drugs or therapies for conditions that result when genes go wrong.