GENOMIC ORGANIZATION OF THE EXTRACELLULAR CODING REGION OF THE HUMAN FGFR4 AND FLT4 GENES - EVOLUTION OF THE GENES ENCODING RECEPTOR TYROSINE KINASES WITH IMMUNOGLOBULIN-LIKE DOMAINS

Receptor tyrosine kinases with five, seven, and three Ig-like domains in their extracellular region are grouped in subclasses IIIa, IIIb, an d IIIc, respectively. Here, we describe the genomic organization of th e extracellular coding region of the human FGFR4 (IIIc) and FLT4 (IIIb ) genes and compare it to that of the human FCFR1(IIIc), KIT, and FMS (IIIa). The results show that while genes belonging to the same subcla ss have an identical exon/intron structure in their extracellular codi ng region-as they do in their intracellular coding region-genes of rel ated subclasses only have a similar exon/intron structure. These resul ts strongly support the hypothesis that the genes of the three subclas ses evolved from a common ancestor by duplications involving entire ge nes, already in pieces. Hypotheses on the origin of introns and on the difference in the number of extracellular Ig-Like domains in the thre e gene subclasses are discussed.