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Surprisingly sloppy yeast genes

The findings suggest the current understanding of transcription networks should be reassessed

By | December 5, 2010

Contrary to popular belief, the gene expression of "housekeeping" proteins in yeast is not synchronized or even coordinated. Instead, these essential genes -- which work together to build important cell complexes like ribosomes and proteasomes -- are turned on and off randomly, researchers report in today's online edition of linkurl:Nature Structural and Molecular Biology.;http://www.nature.com/nsmb/index.html
Fluorescent micrograph of Saccharomyces cerevisiae
linkurl:Philippsen Lab, Biozentrum Basel;http://commons.wikimedia.org/wiki/File:S_cerevisiae_septins.jpg
"We all have our biases about how things work," said senior author linkurl:Robert Singer;http://www.singerlab.org/ of the Albert Einstein College of Medicine in New York. "Sometimes, we're just wrong." The surprising finding may change the way scientists understand and assess some gene transcription networks. "It's fantastic work," said linkurl:Mads Kaern,;http://www.sysbiolab.uottawa.ca/ Canada Research Chair in systems biology at the University of Ottawa, who was not involved in the research. "This challenges the idea that elaborate networks have evolved to regulate this class of genes. That is profound." Multi-protein complexes -- like ribosomes, made up of 80 different proteins -- perform essential functions in cells. Scientists have long assumed the expression of the genes required to assemble such complexes is coordinated because often the resulting proteins have similar abundances in cells. Additionally, it made logical sense that widely varying levels of subunits would result in malformed complexes or a build-up of toxic levels of unused proteins. But linkurl:in 2008,;http://www.ncbi.nlm.nih.gov/pubmed?Db=pubmed&term=Single-RNA+counting+reveals+alternative+modes+of+gene+expression+in+yeast. Singer and colleagues studying the expression of genes in yeast noticed that many constitutive genes -- those transcribed throughout the cell cycle rather than on an as-needed basis -- had irregular, random expression patterns. The unexpected finding led them to predict that the expression of genes needed for multi-protein complexes might not be synchronized, either. When the team measured the expression of several groups of genes -- those encoding subunits of a proteasome, a transcription factor, and RNA polymerase II -- they found that the mRNAs of each group's subunits were no more correlated than the mRNAs of genes that had no functional relationship to each other. Even two alleles of the same gene with identical promoters were not expressed equally. "The genes are essentially clueless," said Singer. "They don't know what they're making or the actual destiny of protein. They're just there, cranking out proteins." In contrast, induced genes -- those triggered by stimuli, such as a nearby toxin or nutrient-rich media -- demonstrated highly coordinated expression. Consequently, the researchers assume that the coordination of protein abundances for complexes happens after transcription. Because many proteins have longer half-lives than mRNA, for example, random fluctuations in mRNA levels may be inconsequential because proteins stick around for significantly longer. Or perhaps chaperone molecules impose checkpoints, stabilizing ribosomes or proteasomes to prevent dissociation until the next subunit arrives. Or both. "We have this bias about cells being efficient, but the more we learn about them, the more inefficient we find out they are," said Singer. "But maybe that's the way biological systems have to work. If they had too many controls, there's a lot more opportunity for things to go wrong." The un-coordinated expression of constitutive genes may have an important evolutionary function, suggested Kaern. "They may make cells more robust, less sensitive to mutations in upstream regulators," he said. If constitutive genes shared one upstream activator to turn them all on simultaneously, a single mutation in that activator could have catastrophic consequences for the cell, he speculated. Overall, the research has important implications for systems biology and researchers studying gene networks of constitutive genes. "This opens up a conceptual door that was previously ignored," said Kaern, who suspects something similar may occur in mice and human cells. "But I think a lot of yeast biologists will not be surprised [this happens in yeast] because they know how sloppy yeast is," he added. "It has a tendency to survive whatever you throw at it." Gandhi, S.J. et al., "Transcription of functionally related constitutive genes is not coordinated," Nat Struct Mol Biol., published online 5 December 2010, doi: 10.1038/nsmb.1934
**__Related stories:__***linkurl:Cheating yeast help group;http://www.the-scientist.com/news/display/57687/
[14th September 2010] *linkurl:Video: Transcription, live;http://www.the-scientist.com/blog/display/57561/
[18th July 2010] *linkurl:Yeast: angiogenesis model? Yup;http://www.the-scientist.com/blog/display/57252/
[23rd March 2010]
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Comments

Avatar of: JAMES STEVENS

JAMES STEVENS

Posts: 2

December 6, 2010

This does not suprise me at all. With all of the other recent findings, I predict that this is the norm in all eukaryotic cell genetic machinery.
Avatar of: DENNIS HOLLENBERG

DENNIS HOLLENBERG

Posts: 26

December 8, 2010

As was said nearly four years ago, neither genes nor their derived products control any biological process: not development, not diseases (including cancer variations), not synapses, ad infinitum.* \n\nRather, all such phenomena occur through the set of dynamics that map precisely to that exhibited by ecosystems. Theoretically, empirically and logically there exists no other possibility.*\n\nTo the extent of the information available to him, Darwin was right. Aside from not being applicable, the Mendelian view is irrelevant to biology generally.\n\nThe leagues of so-called evolutionary biologists and developmental biologists -- to name two cohorts -- who hold that the so-called modern synthesis explains evolution or that "genes" do something could not be more wrong.\n\nA direct effect of this theoretical aberration is our failure to anticipate and cure cancers, not to mention many metabolic, mental and developmental diseases.\n\nIndeed, product of a strident, but misguided committee and its later arrogant supplicants, the neo-darwinian nonsense too long inflicted upon us merely substitutes a mythical "gene" for a deity. Like any flavor of deity, no device is too difficult for the "gene" to accomplish, yet "genes" do nothing.*\n\nNeo-darwinism is merely a parallel of Creationism and, more broadly, of the Newtonian mindset that recoils at the universe's complexity, the devil incarnate. For example, "selfish geners" and creationists should kiss and make up because, for all their imagined differences, they are ecomorphs of a common species.\n\n*my 2007 "On the evolution and dynamics of biological networks" _Revista di biologia/Biology Forum_ 100(1) 93-118.

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Mettler Toledo
BD Biosciences
BD Biosciences