Nucleotide sequence of the dihydrofolate-reductase gene borne by the plasmid R67 and conferring methotrexate resistance

The complete nucleotide sequence of the methotrexate-resistant dihydrofolate reductase (DHFR) gene borne by the plasmid R67 was determined. The gene is 234 bp long and codes for 78 amino acids. The polypeptide deduced from the DNA sequence is in perfect agreement with the previously published amino acid sequence. Comparison of the nucleotide sequence with the one determined for the R388-encoded DHFR indicates that 75% of the nucleotides are conserved in the two genes. The 3′ end of the R67 gene can be modified without altering significantly the activity of the enzyme.