The human genome is composed of long stretches of DNA with distinct GC contents, 
called isochores or GC-content domains. A boundary between two GC-content 
domains in the human NF1 gene region is also a boundary between domains of 
early- and late-replicating sequences and of regions with high and low 
recombination frequencies. The perfect conservation of the GC-content 
distribution in this region between human and mouse demonstrates that GC-content 
stabilizing forces must act regionally on a fine scale at this locus. To further 
elucidate the nature of these forces, we report here on the spectrum of human 
SNPs and base pair substitutions between human and chimpanzee. The results show 
that the mutation rate changes exactly at the GC-content transition zone from 
low values in the GC-poor sequences to high values in GC-rich ones. The GC 
content of the GC-poor sequences can be explained by a bias in favor of GC > AT 
mutations, whereas the GC content of the GC-rich segment may result from a 
fixation bias in favor of AT > GC substitutions. This fixation bias may be 
explained by direct selection by the GC content or by biased gene conversion.