When it comes to the length of a gene, small is beautiful _ or at least,interesting.That's the message in a brief missive from Spain, published in thecurrent issue of Nature. Titled "The smallest known gene," it describesdiscovery of a 21-base-pair sequence, mccA. This encodes a seven-amino-acid antibiotic, microcin C7, which inhibits protein synthesis inEscherichia coli and other Enterobacteriaceae.Principal author of the letter, and of the discovery, is Felipe Moreno,chief of molecular genetics at Madrid's Ramon y Cajal Hospital."To our knowledge," he wrote, "mccA is the smallest gene so farreported." Unlike other ribosomally encoded peptide antibiotics, hisresearch suggests, the microcin gene is a free-standing sequence, ratherthan the functional segment of a longer precursor."Very short open reading frames," Moreno observed, "are usuallythought to have no biological significance." He cited other usefulbacterial genes, 22 and 26-codons long, to support his argument that"small open-reading frames should not be ignored _ or importantbiological functions might be overlooked."A family of microcin antibiotics was isolated in Spain during the1970s, Moreno told BioWorld Today, but the recombinant product hasnot yet achieved commercialization. In a forthcoming paper, he willreport that the little mccA gene requires the help of four other genes,"of more normal size," for biosynthesis in E. coli.He compares mccA's seven-codon length to that of "normal" bacterialgenes, averaging a thousand or so base pairs long, and many humangenes _ e.g., that of Duchenne muscular dystrophy _ in the millions.Moreno worked for a time in the laboratory of Harvard geneticistJonathan Beckwith. He told BioWorld Today, anent the Spanishdiscovery of the tiny gene, "In terms of what we know about biologyand gene expression, et cetera, I don't think it's necessarily surprisingthat you would find that, but up to now nobody had."Concurring with Moreno's pitch in defense of the small, Beckwithadded, "What's interesting about microcins is that, for whatever reason,smaller polypeptides were ignored, maybe because they were not easyto pick up, or filterable, or something like that." n

-- David N. Leff Science Editor

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