Genome Evolution

The evolutionary gain of spliceosomal introns: sequence and phase preferences. Qiu, W.-G. et al. Mol. Biol. Evol. 10 Mar 2003 (doi:10.1093/molbev/msh120)

Whether introns were introduced into the eukaryotic genome early or late in evolution has been a matter of hot debate for some time. Qiu and colleagues have systematically analysed the distribution and reading-frame phase of introns in ten gene families to infer their evolution. They show that the introns were probably not present in the common ancestors of these families and that the bias towards phase-0 introns is probably the result of repeated and recent phase-biased intron gain rather than the retention of an ancestral bias.

Human Genetics

The effects of human population structure on large genetic association studies. Marchini, J. et al. Nature Genet. 28 Mar 2004 (doi:10.1038/ng1337)

Assessing the impact of population stratification on genetic association studies. Freedman, M. L. & Reich, D. et al. Nature Genet. 28 Mar 2004 (doi:10.1038/ng1333)

Undetected population structure can lead to false positives in large-scale association studies. Freedman et al. show that, contrary to what has been proposed, stratification can be difficult to detect with only a few unlinked markers. So, some population stratification might be present even in well-designed studies. Marchini et al. assess the effects of stratification in three example populations and show how even modest stratification has effects that increase with sample size. Their results could inform large-scale study designs.

Technology

A resource for large-scale RNA-interference-based screens in mammals. Paddison, P. J., Silva, J. M., Conklin, D. S. et al. Nature 428, 427–431 (2004)

A large-scale RNAi screen in human cells identifies new components of the p53 pathway. Bers, K. & Hijmans, E. M. et al. Nature 428, 431–437 (2004)

Two groups have created a tremendous resource for carrying out large-scale genetic screens in mammalian cells. Using similar strategies, Hannon and colleagues and Bernards and colleagues constructed short hairpin (sh) RNA-expression libraries, each of which includes ∼25,000 shRNA expression cassettes that target between 8,000 and 10,000 human genes (the first library also targets ∼5,500 mouse genes). shRNA-carrying cassettes can be packaged in retroviruses for transfection and tracked in mixed populations thanks to the use of DNA barcodes. While testing their libraries, Bernards' group identified modulators of p53-dependent proliferation arrest, whereas Hannon's group used it to screen for defects in human proteasome function.