METABOLISM AND EVOLUTION OF HAEMOPHILUS-INFLUENZAE DEDUCED FROM A WHOLE-GENOME COMPARISON WITH ESCHERICHIA-COLI

Background: The 1.83 Megabase (Mb) sequence of the Haemophilus influen zae chromosome, the first completed genome sequence of a cellular life form, has been recently reported, Approximately 75% of the 4.7 Mb gen ome sequence of Escherichia coli is also available. The life styles of the two bacteria are very different - H. influenzae is an obligate pa rasite that lives in human upper respiratory mucosa and can be cultiva ted only on rich media, whereas E. coli is a saprophyte that can grow on minimal media, A detailed comparison of the protein products encode d by these two genomes is expected to provide valuable insights into b acterial cell physiology and genome evolution. Results: We describe th e results of computer analysis of the amino-acid sequences of 1703 put ative proteins encoded by the complete genome of H. influenzae, We det ected sequence similarity to proteins in current databases for 92% of the H. influenzae protein sequences, and at least a general functional prediction was possible for 83%, A comparison of the H. influenzae pr otein sequences with those of 3010 proteins encoded by the sequenced 7 5% of the E. coli genome revealed 1128 pairs of apparent orthologs, wi th an average of 59% identity, In contrast to the high similarity betw een orthologs, the genome organization and the functional repertoire o f genes in the two bacteria were remarkably different, The smaller gen ome size of H. influenzae is explained, to a large extent, by a reduct ion in the number of paralogous genes. There was no long range colinea rity between the E. coli and H. influenzae gene orders, but over 70% o f the orthologous genes were found in short conserved strings, only ab out half of which were operons in E. coli. Superposition of the H. inf luenzae enzyme repertoire upon the known E. coli metabolic pathways al lowed us to reconstruct similar and alternative pathways in H. influen zae and provides an explanation for the known nutritional requirements . Conclusions: By comparing proteins encoded by the two bacterial geno mes, we have shown that extensive gene shuffling and variation in the extent of gene paralogy are major trends in bacterial evolution; this comparison has also allowed us to deduce crucial aspects of the largel y uncharacterized metabolism of H. influenzae.