Emergence and scattering of multiple neurofibromatosis (NF1)-related sequences during hominoid evolution suggest a process of pericentromeric interchromosomal transposition

Type 1 neurofibromatosis (NF1) gene encodes for a member of the GTPaseactivating protein family and is considered to be a tumor suppressor gene.Its very high rate of de novo mutation in humans led us to study a specificfeature of this gene: the presence of numerous NF1-related sequences.According to our results, the human genome contains at least 11 NF1-relatedsequences, nine of which are scattered near centromeric sequences of sevendifferent chromosomes. These NF1-related sequences, whose extent is quitevaried according to loci, are unprocessed copies of the NF1 gene, and bearnumerous mutations. A phylogenetic analysis of the six largest sequencesindicates that they are all derived from a common ancestor, which wouldhave appeared 22-33 million years ago, and was subsequently duplicatedseveral times during hominoid evolution. The most recent duplication andinterchromosomal transposition occurred in the last million yearssuggesting that the process could still be ongoing. Intriguing similaritiesbetween the evolution of alpha- satellite DNA and NF1-related sequencessuggest the involvement of a common genetic mechanism for the generationand pericentric spreading of these NF1 partial copies.