Various new methods have been proposed to predict functional interactions between proteins based on the genomic context of their genes. The types of genomic context that they use are Type I: the fusion of genes; Type II: the conservation of gene-order or co-occurrence of genes in potential operons; and Type III: the co-occurrence of genes across genomes (phylogenetic profiles). Here we compare these types for their coverage, their correlations with various types of functional interaction, and their overlap with homology-based function assignment. We apply the methods to Mycoplasma genitalium, the standard benchmarking genome in computational and experimental genomics. Quantitatively, conservation of gene order is the technique with the highest coverage, applying to 37% of the genes. By combining gene order conservation with gene fusion (6%), the co-occurrence of genes in operons in absence of gene order conservation (8%), and the co-occurrence of genes across genomes (11%), significant context information can be obtained for 50% of the genes (the categories overlap). Qualitatively, we observe that the functional interactions between genes are stronger as the requirements for physical neighborhood on the genome are more stringent, while the fraction of potential false positives decreases. Moreover, only in cases in which gene order is conserved in a substantial fraction of the genomes, in this case six out of twenty-five, does a single type of functional interaction (physical interaction) clearly dominate (>80%). In other cases, complementary function information from homology searches, which is available for most of the genes with significant genomic context, is essential to predict the type of interaction. Using a combination of genomic context and homology searches, new functional features can be predicted for 10% of M. genitalium genes.

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Nature © Macmillan Publishers Ltd 19988 the hippocampus in vitro 1-3 . Although the mechanisms by which Dzȋ causes neuronal death are not fully understood, in vitro results suggest that an increase in oxidative stress and destabilization of calcium homeostasis 2,3 are involved.However, in contrast to these in vitro observations 2-4 , only a slight neurotoxicity results when Dzȋ is directly administered to the brain 5,6 , perhaps because of the rapid efflux of injected compounds from this organ.In this respect another organ, the retina, offers several advantages. It is an integral part of the central nervous system; its structure is well organized; and, because it is a closed system, injected compounds remain in the vitreous body for a long time 7 .We investigated the cytotoxic effects of Dzȋ on retinal cells after intravitreal injection and the amelioration of these effects by the antioxidant vitamin E. The technique used to assess apoptosis and therefore cytotoxicity was terminal deoxynucleotidyl transferase dUTP-end-labelling (TUNEL) staining. This technique identifies the 3፱ ends of DNA strands -a phenomenon resulting from the fragmentation of DNA that occurs in apoptotic cells.When the retinas of rats were injected with either aged Dzȋ 1-42 or aged Dzȋ 1-40 (aggregated; incubated for 4 days at 37 °C), a distinct band of TUNEL-positive photoreceptor cells was evident in the retina's outer nuclear layer. However, in the inner nuclear layer and ganglion cell layer, only a few scattered cells were TUNEL positive (Fig. 1a). This suggests that proximity to the Dzȋ injection site is not essential for cytotoxicity.In addition, all retinas injected with the freshly prepared, 'new' Dzȋ 1-40 behaved like vehicle-injected and uninjected retinas in showing only occasional TUNEL-positive cells (Fig. 1c). Therefore the cytotoxic effect was specific to treatment with aggregated Dzȋ. Moreover, unlike active aged Dzȋ 1-40 , inactive aged reverse Dzȋ 40-1 did not induce any changes in photoreceptor cells (Fig. 1c).No DNA fragmentation was seen in the glial cells. But, as with cultured neural cells in vitro 8 , treatment with Aȋ 1-42 or Aȋ 1-40 severely decreased Bcl-2 immunoreactivity in the endfeet and proximal part of radial processes of Müller glial cells.In vitro studies also suggested that Dzȋ causes an accumulation of hydrogen peroxide and lipid peroxides in the cells, and that antioxidants protect cells from Dzȋ toxicity 2,3 . We found that TUNEL-positive photoreceptor cells in retinas that had been pretreated with vitamin E (1.3 micrograms per 3 microlitres) showed a reduction of about 65% compared with retinas treated with aged Dzȋ 1-42 (Fig. 1). This indicates that Dzȋ cytotoxicity is caused, at least partly, by a free-radical mechanism.Doubts have been raised in the past about extrapolating in vitro findings on Dzȋ cytotoxicity to the situation in vivo. Our results show that some of the proposed mechanisms underlying Dzȋ neurotoxicity do operate in vivo. In addition, the closed 'retina-vitreal' system we describe should serve as an ...

The tuf gene of eubacteria, encoding the EF-tu elongation factor, was duplicated early in the evolution of the taxon. Phylogenetic and genomic location analysis of 20 complete eubacterial genomes suggests that this ancient duplication has been differentially lost and maintained in eubacteria. ß