Localization of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) in the rat to chromosome 4 and implications for the evolution of mammalian chromosomes

Abstract

We have isolated a partial cDNA encoding the cystic fibrosis transmembrane conductance regulator (CFTR) in the rat. This cDNA hybridizes to a 6.1-kb RNA transcript from the human T84 epithelial cell line and a similarly sized transcript from the rat parotid gland. The nucleotide sequence of this cDNA shows 80.5% identity to the human CFTR cDNA sequence, and the deduced amino acid sequence of rat CFTR shows 75.5% identity to the amino acid sequence of human CFTR. We have used this cDNA to map the location of the gene encoding CFTR to rat chromosome 4. This result places CFTR within a syntenic group on rat chromosome 4 and on human chromosome 7 that includes the genes encoding interleukin 6 (IL6), erythropoietin (EPO), P-glycoprotein 1 (PGY1), and T cell receptor beta chain (TCRB). This group is divided between chromosomes 5 and 6 in the mouse. Mapping of CFTR to rat chromosome 4 shows that this syntenic group has been divided in the mouse lineage during the past 15 million years and further localizes that breakpoint to a sequence homologous to the human chromosome 7q21.1 and 7q32 region. Similarly, a group of five genes, CFTR, TCRB, HOX1, parathyroid hormone-like hormone (PTHLH), and Kirsten rat sarcoma 2 viral (v-Ki-ras2) oncogene homolog (KRAS2), is syntenic on rat chromosome 4 and mouse chromosome 6, but is divided between human chromosomes 7 and 12. These data suggest that the ancestral mammalian chromosome appeared as the present day rat chromosome 4, with all six genes grouped together, and that chromosomal breakages have occurred in the mouse and human lineages since the mammalian divergence.