Good Mutation, Bad Mutation

Science's STKE  05 Aug 2003:
Vol. 2003, Issue 194, pp. tw307-TW307
DOI: 10.1126/stke.2003.194.tw307

Among a few human genes, there has long been evidence for a significant difference in specific mutations between males and females and an increase in mutation with paternal age. The gene for fibroblast growth factor receptor 2, FGFR2, encodes a receptor tyrosine kinase protein, and mutation of nucleotide 755 of this gene frequently results in offspring with conditions such as Apert syndrome, which causes craniofacial and limb malformations. Goriely et al. (see the Perspective by Crow) now examine the prevalence of FGFR2 mutations in sperm and show the age dependence of these events. The mutations occur infrequently but become enriched through cellular selection within the testis. Hence, the mutation that occurs is one that is good for the spermatogonial cell in which it arises, but bad for any resulting offspring.

A. Goriely, G. A. T. McVean, M. Röjmyr, B. Ingemarsson, A. O. M. Wilkie, Evidence for selective advantage of pathogenic FGFR2 mutations in the male germ line. Science 301, 643-646 (2003). [Abstract] [Full Text]

J. F. Crow, There's something curious about paternal-age effects. Science 301, 606-607 (2003). [Summary] [Full Text]