Hiding From the Noise - Essential Genes Cluster in Open Chromatin?

We've previously discussed on the bayblab how the same transgene can provoke different murine phenotypes depending on which genomic locus it is expressed from. We've also discussed work demonstrating how noisy gene expression seems to be caused by stochastic bursts of mRNA transcription. A new paper in Nature Genetics ties together these ideas with the observation that essential genes tend to physically cluster within specific regions of genomes.

Based on the reasoning that transcriptional noise arises from the stochastic relaxation of otherwise closed chromatin, Batada and Hurst argue that essential eukaryotic genes tend to cluster within regions of open chromatin because these regions are relatively free from transcriptional noise. This would minimize the possibility of random fluctuations in expression that would kill the cell and therefore provide a selective advantage to those cells whose essential genes cluster together in less noisy regions. They present bioinformatic analyses of yeast data that seem to support this idea.

I like the idea, but am not totally sold on the notion of "essentialness". Yeast essential genes are based on those which are lethal when mutated in yeast grown under the warm and loving conditions of laboratory culture. However, the yeast genome did not evolve in the lab, it evolved in much harsher and variable natural environments. The the real set of essential genes is likely to be much larger than defined here, in fact it may include the whole genome as it is likely that each gene was essential at some point in yeast evolution. This said, even in natural environments, there maybe a spectrum of gene essential-ness, with some genes essential over a broader range of conditions, or longer evolutionary time-span than others. Thus the lab essential genes may actually reflect the core set of "most essential genes". But can we take this for granted?

Mitochondrial Madness

Our often-neglected bacterial endosymbionts the mitochondria seem to have their fingers in all aspects of eukaryotic cell functioning. Not only do they make us ATP and tell our cells when to die, they even have their own genome, which they can replicate, transcribe and translate all on their own. But mitochondria don't just use proteins encoded in their own genomes; they've also got some out on loan from the nucleus. And this is where the madness begins. Somehow this excellent Molecular Cell review on mitochondrial transcription found its way onto my lab bench, so I read it. Here are a few of the mind-blowing facts you can discover therein:

• The eukaryotic single-subunit mitochondrial RNA polymerase was ganked from bacterial viruses (bacteriophage T3/T7), and has no relation to those encoded by bacteria themselves.

• Even weirder, the phage-like mtRNA polymerase is encoded in the nuclear genome of eukaryotes. Interstingly, an isoform of mtRNA polymerase lacking a mitochondrial localization signal performs transcription of nuclear-encoded genes in the nucleus (RNA pol IV).

• The amino-terminal domain of yeast mtRNA polymerase has diverged from its phage ancestry, and has evolved to mediate coupling between mitochondrial transcription and translation. In fact, mutations in the ATD lead to deficiencies in mitochondrially-encoded OXPHOS enzymes and thereby decrease lifespan in yeast.

• What? Mitochondrial translation? What's up with that? Nobody really knows...

Also, check out this wicked album of artistic renditions of cells by Gary Carlson which I ganked the above photo from. Nice job Gary!