Functional Genomics

Genomic gene clustering analysis of pathways in eukaryotes. Lee, M. J. & Sonnhammer, E. L. L. Genome Res. 13, 875–882 (2003)

Although operons are rare in eukaryotes, genes that act in the same pathways might still be clustered. The authors looked for clustering in five eukaryotic genomes for genes that have been assigned to the same pathway in the KEGG database. Although genes associated with 30–98% of pathways cluster to some extent, surprisingly, there is little conservation between genomes as to which genes are clustered, perhaps reflecting lineage-specific evolutionary-events.

Functional Genomics

Discovering novel cis -regulatory motifs using functional networks. Etteiller, L. M. et al. Genome Res. 13, 883–895 (2003)

Data from DNA-binding experiments, microarrays and genome comparisons have been used to facilitate regulatory-motif discovery. These authors use protein–protein interactions and metabolic networks in combination with Saccharomyces cerevisiae genome data to predict upstream regulatory motifs. They describe 42 potential sites, some of which are new and are associated with genes that are probably co-regulated. Their results show that interacting proteins are often transcriptionally coordinated, even if there is no evidence for their co-regulation in gene-expression data sets.

Mouse Models

Mutations in dynein link motor neuron degeneration to defects in retrograde transport. Hafezparast, M. et al. Science 300, 808–812 (2003)

The genetic basis of most motor neuron diseases (MND) is unknown. But a promising breakthrough has been made from the study of two mouse mutants — Legs at odd angles and Cramping 1. These mice have progressive neurodegenerative disorders and share a similar pathology to human MND. Both mutants carry a missense point mutation in the cytoplasmic dynein heavy chain, which is needed for microtubule-mediated retrograde transport in axons.

Cloning

Molecular correlates of primate nuclear transfer failures. Simerly, C. et al. Science 300, 225–227 (2003)

So far, no one has successfully cloned a primate, let alone a human, by nuclear transfer. Cloned rhesus monkey embryos fail to develop beyond early stages because many of the cells are aneuploid as a result of aberrant mitotic-spindle formation. Two proteins, NuMA and HSET, are needed for correct spindle organization, but in primates — unlike other mammals — these proteins are exclusively associated with the chromosomes in unfertilized egg cells. As these chromosomes are removed during nuclear transfer, spindle organization is disorganized in primates and chromosome segregation fails.