MOLECULAR EVOLUTION OF THE GENES ENCODING RECEPTOR TYROSINE KINASE WITH IMMUNOGLOBULIN-LIKE DOMAINS

Receptor tyrosine kinases (RTK) with five, three, or seven immunoglobu linlike domains in their extracellular regions are classified as subcl asses III, IV, and V, respectively. Conservation of the exon/intron st ructure of the downstream part of the human KIT, FMS, and FLT3 genes t hat encode RTK of subclass III together with the particular chromosoma l localization of these genes suggests that RTKIII genes have evolved from a common ancestor by cis and trans duplications. To strengthen th is model of evolution and to determine if it can be extended to RTKIV and V genes, we constructed a phylogenetic tree of RTKIII, IV, and V o n the basis of a multiple alignment of their catalytic tyrosine kinase domain sequences and determined the exon/intron structure of PDGFRA ( subclass III), FGFR4 (subclass IV), and FLT4 (subclass V) genes in the ir downstream part. Phylogenetic analyses with amino acid or nucleotid e sequences both resulted in one most parsimonious tree. The phylogene tic trees obtained indicate that all three subclasses are well individ uated and that RTKIII and RTKV are closer to each other than RTKIV. Fu rthermore, RTKIII and FLT4 (subclass V) genes possess the same exon/in tron structure in their downstream part while the structure of the RTK IV genes is very similar to that of RTKIII and FLT4. Both approaches a re in complete agreement and indicate that RTKIII, IV, and V genes mos t probably evolved from a common ancestor already ''in pieces'' by suc cessive duplications involving entire genes.