Comparative Whole Genome Sequence Analysis of Corynebacteria

Abstract

Complete genome sequences are available for three corynebacterial species: Corynebacterium glutamicum, which is widely used for industrial amino acid production by fermentation; Corynebacterium efficiens, which produces glutamic acid at a higher temperature than C. glutamicum; and Corynebacterium diphtheriae, which is a well-known pathogenic bacterium. Comparative genomic studies highlighted the evolutionary mechanisms underlying various aspects of the functional differentiation of these species, such as the unique metabolic features and thermostability of C. efficiens. The GC content of the C. efficiens genome amounted to 63.1 %, which was approximately 10 % higher than those of C. glutamicum and C. diphtheriae were. This difference was reflected in codon usage and nucleotide substitutions. Analyzing orthologous gene pairs with 60–95 % amino acid sequence identity between C. efficiens and C. glutamicum revealed a significant bias in amino acid substitutions. In particular, accumulations of three asymmetrical amino acid substitutions (lysine to arginine, serine to alanine, and serine to threonine) were associated with the thermostability and increased GC content of C. efficiens. A phylogenetic tree constructed using Mycobacterium and Streptomyces as outgroups indicated that the common ancestor of the corynebacteria was likely to have possessed most of the gene sets necessary for amino acid production. C. diphtheriae appeared to have lost the genes responsible for amino acid production. Glutamate overproduction in C. glutamicum was induced by a shortage of biotin, and this bacterium showed an incomplete biotin biosynthesis pathway. By contrast, C. diphtheriae might have acquired the complete biotin biosynthesis pathway by horizontal gene transfer. This process could have affected metabolic regulation in the corynebacteria following the loss of the glutamate overproduction mechanism in C. diphtheriae. Our findings suggest that dynamic genome evolution has been a motivational force for functional differentiation among the corynebacteria.