Evolution

Evolutionary EST analysis identifies rapidly evolving male reproductive proteins in Drosophila. Swanson, W. J. et al. Proc. Natl Acad. Sci. USA 98, 7375–7379 (2001) [PubMed]

Reproductive proteins are likely candidates for causing the rapid divergence between closely related species, as their modification favours adaptive divergence. To test this hypothesis, Swanson et al. compared the sequences of 285 ESTs (expressed sequence tags) isolated from the male accessory glands — which secrete seminal-fluid proteins — of Drosophila simulans and D. melanogaster. 11% of the 176 genes identified showed evidence of positive selection, and the 57 newly identified accessory gland genes should become candidate genes for further positive selection studies.

Cancer genetics

Mitotic recombination effects homozygosity for NF1 germline mutations in neurofibromas. Serra, E. et al. Nature Genet. 28, 294–296 (2001) [PubMed]

Neurofibromatosis type 1 (NF1) is an autosomal-dominant disorder caused by mutations in the NF1 tumour suppressor gene. Of the many cell types seen in NF1 nerve-sheath tumours, only Schwann cells are homozygous for NF1 mutations. Through molecular and in situ hybridization of cultured Schwann cells, this paper shows that loss of heterozygosity for NF1 occurs by mitotic recombination. As there is inter-individual variability in mitotic recombination rates, genes that control this phenomenon might act as modifier genes for susceptibility to NF1 and other cancers.

Human genetics

Charcot–Marie–Tooth disease type 2A caused by mutation in a microtubule motor K1F1Bβ. Zhao, C. et al. Cell 105, 587–597 (2001). [PubMed]

CMT2A is a dominant subtype of Charcot–Marie–Tooth disease (CMT) — the most commonly inherited human peripheral neuropathy — that maps to 1p35–36. When Zhao et al. knocked out the mouse β isoform of K1f1B — which encodes a motor protein belonging to the kinesin superfamily — null mutants died at birth with multiple neurological abnormalities, and heterozygotes developed progressive muscle weakness and defective synaptic vesicle transport. This CMT-like phenotype and the chromosome-1 map location of K1f1B lead the authors to analyse the gene in CMT2A patients, in whom they found loss-of-function mutations in the motor domain of K1F1B. As axons lack protein-synthesis machinery, their survival depends on the transport of essential proteins. Haploinsufficiency for K1f1B might therefore reduce levels of synaptic vesicle transport of essential factors and receptors, leading to the impairment of nerve endings and to the decreased survival of peripheral neurons.