Emergence of the keratinocyte growth factor multigene family during the great ape radiation.
The structural gene for human keratinocyte growth factor (KGF), a member of the fibroblast growth factor family, consists of three coding exons and two introns typical of other fibroblast growth factor loci. A portion of the KGF gene, located on chromosome 15, is amplified to approximately 16 copies in the human genome, and these highly related copies (which consist of exon 2, exon 3, the intron between them, and a 3' noncoding segment of the KGF transcript) are dispersed to multiple human chromosomes. The KGF-like sequences are transcriptionally active, differentially regulated in various tissues, and composed of three distinct classes of coding sequences that are 5% divergent from each other and from the authentic KGF sequence. Multiple copies of KGF-like genes were also discovered in the genomic DNAs of chimpanzee and gorilla but were not found in lesser apes (gibbon), Old World monkeys (African green monkey and macaques), mice, or chickens. The pattern of evolutionary occurrence suggests that a primordial KGF gene was amplified and chromosomally dispersed subsequent to the divergence of orangutan from African apes but before the trichotomous divergence of human, chimpanzee, and gorilla 5-8 million years ago. The appearance of a transcriptionally active and chromosomally dispersed multigene KGF family may have implications in the evolution of the great apes and humans.
Kelley
M J
MJ
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892.
Pech
M
M
Seuanez
H N
HN
Rubin
J S
JS
O'Brien
S J
SJ
Aaronson
S A
SA
D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D002522:Chlorocebus aethiops / Q000235:genetics; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D006071:Gorilla gorilla / Q000235:genetics; D006133:Growth Substances / Q000235:genetics*; D015186:Hominidae / Q000235:genetics; D006801:Humans; D008253:Macaca mulatta / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D009838:Oligodeoxyribonucleotides; D002679:Pan troglodytes / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D011148:Pongo pygmaeus / Q000235:genetics; D011323:Primates / Q000235:genetics*; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid
C496453:FGF7 protein, human; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D009838:Oligodeoxyribonucleotides; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D004247:DNA