Developmental biology

Male-to-female sex reversal in mice lacking fibroblast growth factor 9. Colvin, J. S. et al. Cell 104 , 875–889 (2001) [PubMed]

Fibroblast-growth-factor (FGF) signalling has been implicated in many aspects of development; and now Colvin et al. describe a new function for Fgf9 in testicular embryogenesis. Their analysis of Fgf9 knockout mice identified a variable gonadal phenotype, ranging from testicular hypoplasia to complete sex reversal. They found that Fgf9 acts early in the commitment to male development and regulates many Sry-dependent processes, including Sertoli-cell differentiation and mesonephric-cell migration. The authors suggest that FGF signalling could induce male development in the absence of Sry — an important finding as many mammals lack Sry — and that FGF9 mutations might contribute to human sex reversal.

Human genetics

An alternative mode of translation permits production of a variant NBS1 protein from the common Nijmegen breakage syndrome allele. Maser, R. S. et al. Nature Genet. 27 , 417–421 (2001) [PubMed]

Around 90% of patients with Nijmegen breakage syndrome (NBS) are homozygous for a small deletion that prematurely truncates the NBS1 transcript. As loss of Nbs1 is lethal in mice, the authors investigated whether this truncation allele encodes a hypomorph. Surprisingly, they found two proteins translated from the truncated transcript — NBS1p27, the predicted truncated protein, and the larger NBS1p70, which lacks the NBS1 amino-terminus. NBS1p70 is produced from an internal translation initiation site in NBS1 messenger RNA that allows an open reading frame from the deletion transcript to be translated. Unlike NBS1p27, NBS1p70 still associates with the MRE11 DNA-repair complex, possibly diminishing the NBS phenotype.

Techniques

DNA shuffling method for generating highly recombined genes and evolved genomes. Coco, W. M. et al. Nature Biotechnol. 19 , 354–359 (2001) [PubMed]

DNA shuffling, or chimeragenesis, has been used to evolve gene families in vitro. These techniques create gene libraries in which original sequence polymorphisms are recombined at random to generate new sequence combinations. Most strategies achieve approximately four crossover events per gene. Coco et al. now report a new approach called RACHITT (random chimeragenesis on transient template), in which single-stranded DNA fragments are hybridized to a transient DNA template, generating 14 crossovers per gene and high recombination frequencies, even between polymorphisms that are less than 10 bases apart in regions of high and low homology. Using RACHITT, the authors created new enzyme combinations for the desulphurization of fossil fuels.