CORRELATION BETWEEN THE CHROMOSOMAL LOCATION OF ENZYME GENES AND THE ORGANIZATION OF METABOLIC PATHWAYS

Hiroyuki Ogata, Hidemasa Bono, Susumu Goto, Wataru Fujibuchi and Minoru Kanehisa
Institute for Chemical Research, Kyoto University,
Gokasho, Uji, Kyoto 611, Japan

In the time of successive completion of the genomic sequences, computational methods have become essential tools towards understanding how biological functions are coded on the genomes. A recently developed database by Kanehisa et al. dealing with the metabolic pathways provides new opportunities for characterizing the pathway formation and the gene organization. The database named KEGG stores a wide coverage of the known metabolic pathways in a computable form called "binary relations", which enabled us to conduct extensive comparisons between the pathway forms and the genome structure.

In this study we focused on whether the functional link of two enzymes measured by the path length, i.e., the length of the pathway which is one for the adjacent pair of enzymes, had any relation to the physical distance of the respective genes along the chromosome. We calculated the mean path length of all the pairs of the enzymes that appear within a given window of the chromosome for E. coli.

As the result, a significant correlation was observed between the locality of the enzymes on the pathways and the locality of the genes on the chromosome. The mean path length decreased in accordance with the decreasing window size. If the enzymes appearing in close positions on the metabolic pathways are coded randomly on the chromosome, the average values of path length are expected to be the same for different window sizes. We considered that this correlation would be due to the existence of functionally related enzymes coding segments (FRECS), that encode enzymes playing their rolls at close positions on the metabolic pathways. Enzymes in the same operon and duplicated enzymes were examined as contributors of these FRECS. Actually the former contributed to the tendency in a significant degree (~60%), but the latter did not. We will discuss on these results in detail, in addition to the investigation on the remaining FRECS that had no connection to the known operons.

Meeting on "Genome Mapping & Sequencing"
(May 14-18, 1997, Cold Spring Harbor Laboratory, New York)