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Problem statement: Dihydrofolate Reductase (DHFR) and Thymidylate Synthase (TS) exist as bifunctional enzymes coded into unique polypeptide chain in protozoans. Bifunctional DHFR-TS is associated with an increase in the enzymatic activity by channeling the substrate between the active sites. In some bacteria, DHFR and TS genes are neighbors in the genome, whereas in others, they are located millions of base pairs apart. Gene neighboring gained importance in evolution because it was found to promote the interaction between expressed proteins in gene clusters. Co-expression of neighboring genes might favor protein associations, increasing the enzymatic efficiency. The basis of genomic evolution that leads to gene ordering is not totally understood; however, one could suppose that increasing the efficiency of metabolic pathways could work as an evolutionary pressure to get genes together in the genome of an organism. Approach: In this study, phylogenetic analysis of DHFR and TS sequences and the genomic distance between these genes in bacteria were measured. Results: No significant correlation was found between genomic distances, in base pairs, of DHFR and TS genes and phylogenetic distance among the studied bacteria. Conclusion/Recommendations: This suggested that DHFR and TS enzymes clusters, even if they are coexpressed, might not exert a pivotal role in natural selection of bacteria

Genomic Distance between Thymidylate Synthase and Dihydrofolate Reductase Genes Does Not Correlate With Phylogenetic Evolution in Bacteria