Abstract
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.
Highlights
Study of gene ordering has become a promising area of genetics since the sequencing of numerous eukaryotic and prokaryotic genomes in the 1990’s
Phylogenetic distance is a good parameter to measure the evolutionary distance between organisms and a phylogenetic distance matrix can be constructed from a set of DNA or protein sequences of homologous genes from such organisms (Tamames et al, 1997; Lathe et al, 2000; Huynen and Bork, 1998; Aravind, 2000; Tamames, 2001; Rogozin et al, 2004; Dandekar et al, 1998)
Distance matrix calculated from Dihydrofolate Reductase (DHFR) sequences was used to analyze how well the evolutional distance between the studied species correlated with the distance between Thymidylate Synthase (TS) and DHFR genes in the bacterial genomes
Summary
Study of gene ordering has become a promising area of genetics since the sequencing of numerous eukaryotic and prokaryotic genomes in the 1990’s. TS and DHFR are enzymes that work together in successive reactions of folate synthesis pathway These proteins exist, in some protozoans, as bifunctional enzymes, which are important in channeling the substrate between TS and DHFR active sites (Atreya and Anderson, 2004; Miles et al, 1999; Trujillo et al, 1997). These genes are neighbors in some bacterial genomes, whereas they are located millions of base pairs apart Gene neighboring hypothesis of evolution in prokaryotes demands more studies, it is supposed that TS and DHFR genes were not evolutionarily driven to get closer in bacterial genomes in the studied bacterial evolution
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