Evolution

Noise minimization in eukaryotic gene expression.. Fraser, H. B. et al. PloS Biol. 27 Apr 2004 (doi:10.1371/journal.pbio.0020137)

Until now, the functional and evolutionary significance of stochastic ('noisy') fluctuations in the rates of protein production was a mystery. Michael Eisen and colleagues have developed a model of stochastic gene expression in yeast to test their hypothesis that genes that encode subunits of multiprotein complexes or that cause lethality when deleted would be sensitive to such variation. Their estimates of the noise in protein production for most yeast genes confirm this hypothesis and indicate that natural selection minimizes noise in gene expression.

Cancer genetics

Impact of the KU80 pathway on NHEJ-induced genome rearrangements on mammalian cells.. Guirouilh-Barbat, J. et al. Mol. Cell 14, 611–623 (2004)

The genomes of cancer cells are often unstable and undergo rearrangements. Non-homologous end joining (NHEJ), a process that joins broken ends of double-strand breaks (DSBs) in DNA, is generally associated with maintaining mammalian genome stability. Josée Guirouilh-Barbat and colleagues now show that NHEJ might occur in two-thirds of DSB repairs. Surprisingly, their data indicate that this pathway often incorporates broken DNA into new locations and so accounts for many genome rearrangements that are seen in cancer cells.

Ageing

Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-γ.. Picard, F. et al. Nature 2 June 2004 (doi:10.1038/nature02583)

Premature ageing in mice expressing defective mitochondrial DNA polymerase.. Trifunovic, A. et al. Nature 429, 417–423 (2004)

Two studies provide separate molecular explanations for the ageing process in mammals. In yeast, the SIR2 gene is the link between calorie restriction and an extended lifespan. Leonard Guarente and colleagues have now investigated how Sirt1 (sirtuin 1), the mammalian version of SIR2, mediates the same effect in the mouse. Fat reduction extends the mouse lifespan, and the authors have shown that this is caused by the ability of SIRT1 to promote fat mobilization in adipocytes by repressing the fat regulator PPAR-γ during food deprivation. Nils-Göran Larsson and colleagues focussed instead on the mitochondrial DNA (mtDNA), which is known to accumulate mutations with age. Mice that were defective for the mtDNA polymerase PolgA — because they expressed a nuclear knock-in mutation that abolished the proofreading ability of the polymerase — accumulated 3–5 times the number of point mutations, aged prematurely and developed age-related features, such as baldness and reduced fertility. This clever experiment supports the view that mtDNA mutations are the cause rather than the consequence of ageing.