Molecular phylogeny of F nu 1

Alleles at the F nu 1 gene of inbred mice confer resistance to infection an d spread of vertically or horizontally transmitted murine leukemia viruses (MuLV). The nucleotide sequence of F nu 1 bears similarity to the gag of a human endogenous retrovirus, HERV-L, but is more closely related to the gag -coding sequence of a newly described class of HERV-L-related mouse endogen ous retroviruses designated MuERV-L. Both observations suggest an origin of F nu 1 from endogenous gag sequences. The molecular definition of F nu 1 p rovided an opportunity to determine the phylogeny of the gene among wild mi ce and its relation to MuERV-L. PCR primers, chosen to include most of the coding region of F nu 1 for both the n and b alleles, were used to amplify sequences from animals of the genus Mus, which were then sequenced. Closely related products were obtained from almost all animals examined that evolv ed after the separation from Rattus, in which the homologous gene was shown to be absent. A phylogenetic tree generated with F nu 1 sequence data diff ers noticeably from that developed with sequence data from other genes. In addition, nonsynonymous changes were found to be present twice as frequentl y as synonymous changes, a fact that departs from the standard behavior of a structural gene. These observations suggest that the F nu 1 gene may have been subjected to possible horizontal transfers as well as to positive Dar winian selection.