Genomic organization of the flt-1 gene encoding for Vascular Endothelial Growth Factor (VEGF) receptor-1 suggests an intimate evolutionary relationship between the 7-Ig and the 5-Ig tyrosine kinase receptors

The flt-1 tyrosine kinase gene encodes a high affinity receptor for Vascular Endothelial Growth Factor, and belongs to the so-called '7-Ig' or flt gene family which has characteristics of 7-Immunoglobulin (Ig)-like domains in the extracellular region. This is structurally distantly related to 5-Ig domain-coataining receptors such as Fms/Kit/PDGF-R. However, the whole genomic organization for any 7-Ig receptor gene has not been determined yet. To examine the genomic structure of flt-1 and the evolutionary relationship between genes of the 7-Ig and 5-Ig receptor families, we isolated the mouse genomic DNAs carrying all exons of the flt-1 gene. The mouse flt-1 gene consisted of 30 exons, whose exon-intron boundaries were highly related to those in the 5-Ig receptor genes, except for the amino terminal region. The sequences corresponding to the first and second Ig-domains in the flt-1 gene were encoded by four exons, whereas this region was encoded by only two exons in the 5-Ig receptor genes. These results raise the interesting possibility that deletion or insertion mutations of introns in one of these receptor genes took place in the evolutionary generation of the other receptor genes. (C) 1998 Elsevier Science B.V.