Image: Differences in the amino acid content of yeast
strains with individual genes knocked out have shown how many genes
are involved in metabolism.
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.
Yeast cells have about 6,000 genes, compared with around 20,000
in humans. Prior to this study, scientists didn't know the exact
role of many of the genes in either species.
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.
The paper, 'Functional metabolomics pictures the yeast
biosynthethic regulome', is published inCell.