The Nuclear Factor I (NFI) family of DNA-binding proteins is essential for
adenovirus DNA replication and the transcription of many cellular genes. Ma
mmals have four genes encoding NFI. proteins, C. elegans has only a single
NFI gene, and prokaryotes have none. To assess the relationship between mem
bers of this unusually small family of transcription/replication factors, w
e mapped the chromosomal locations of the four murine NFI genes and analyze
d the exons encoding the DNA-binding domains of the mouse, Amphioxus, and C
. elegans NFI genes. The four murine NFI genes are on Chrs 4 (Nfia and Nfib
), 8 (Nfix), and 10 (Nfic), suggesting early duplication of the genes and d
ispersal throughout the genome. The DNA-binding domains of all four NFI gen
es are encoded by large (532 bp) exons with identical splice acceptor and d
onor sites in each. In contrast, the C. elegans nfi-1 gene has four phased
introns interrupting this DNA-binding, domain-encoding exon, and the last e
xon extends 213 bp past the splice site used in all four murine genes. In a
ddition, the introns present in C. elegans nfi-1 are missing from the NFI g
enes of Amphioxus and all mammalian genomes examined. This analysis of the
exon structure of the C. elegans and murine NFI genes indicates that the mu
rine genes were probably generated by duplication of a C. elegans-like ance
stral gene, but that significant changes have occurred in the genomic organ
ization of either the C. elegans or murine NFI genes during evolution.