Genome evolution

Natural selection on human microRNA binding sites inferred from SNP data. Chen, K. & Rajewski, N. Nature Genet. 29 October 2006 (doi: 10.1038/ng1910)

Using SNP genotype data from three human populations to study cis-regulatory sites in the human genome, these authors show that negative selection is stronger on computationally predicted microRNA (miRNA) binding sites than on other conserved 3′ UTR sequence motifs. This finding provides evidence for the contribution of miRNAs to fitness. This approach, which can be extended to other types of cis-regulatory sites, indicated that 30–50% of unconserved miRNA binding sites can be functional. The probably deleterious effects of polymorphisms in predicted miRNA binding sites make them candidates for disease-causing variants.

Genomics

The genome of the sea urchin Strongylocentrotus purpuratus. Sea Urchin Genome Sequencing Consortium Science 314, 941–952 (2006)

Sea urchin embryos have been extensively used in developmental, molecular, evolutionary and cell biology. The sequencing and analysis of the sea urchin genome has now been reported. The 814 Mb genome was sequenced at ∼8× coverage using shotgun cloning and BAC sequences, and is estimated to contain ∼23,300 genes. Genome analysis revealed a wealth of information about sea urchin biology (including a surprisingly sophisticated immune system), as well as vertebrate and chordate genome evolution.

Cancer genetics

The BRCA1/BARD1 heterodimer modulates RAN-dependent mitotic spindle assembly. Joukov, V. et al. Cell 127, 539–552 (2006)

The tumour suppressor BRCA1 functions in maintaining genomic integrity, but the details of how it does so have not been completely determined. Using Xenopus laevis egg extracts and human cells, this study demonstrates a previously unknown role of BRCA1 in mitotic spindle assembly. Heterodimers of BRCA1 and BARD1 work downstream of the RAN pathway to modulate the activity of spindle-pole proteins, probably through their E3 ubiquitin ligase activity. Defects in spindle-pole formation that lead to chromosome-segregation defects and aneuploidy might contribute to the genomic instability that is observed in BRCA1-deficient tumour cells.

DNA repair

Age-dependent usage of double-strand-break repair pathways. Preston, C. R. et al. Curr. Biol. 16, 2009–2015 (2006)

Cells have evolved different mechanisms of DNA repair to preserve genetic information. The authors analysed the amount and quality of DNA double-strand break repair in Drosophila premeiotic germ cells and found that the relative use of different repair pathways changes as the organism ages. In particular, cells in old individuals use slow but accurate homologous recombination, whereas cells in younger flies opt for faster but error-prone repair mechanisms. This might contribute to the accumulation of genetic damage that takes place during ageing.