How many genes does a bacterium need?

Take a look at today's bacteria. If push came to shove, how many of their genes could the microbes do without? Or to pose the query another way, what is the minimum number of genes sufficient for a modern bacterial cell?

In years past, such questions would have elicited replies no more scientific than calculations of how many angels can dance on the head of a pin. Yet in the last 15 months, researchers have unveiled the complete genetic complements of several single-celled organisms, including two bacteria. This new information has allowed investigators to take a serious stab at what were previously fanciful inquiries.

Relying largely upon a comparison of the bacteria whose full gene sets, or genomes, have been laid bare, two scientists now conclude that a mere 256 or so genes may be necessary and sufficient for the modern cell. Arcady R.

Mushegian and Eugene V. Koonin, both of the National Center for Biotechnology Information in Bethesda, Md., report their analysis in the Sept. 17

Proceedings of the National Academy of Sciences.

The researchers propose that determining the minimal genetic requirements of a modern single-celled organism may aid attempts to reconstruct the genome of the ancestral microorganism from which all current life presumably evolved. "Eventually, backwards extrapolation from the minimal gene set may lead close to the origin of life itself," Mushegian and Koonin write.

The two investigators constructed their minimal genome after examining the genes of Haemophilus influenzae and Mycoplasma genitalium, whose genomes were described last year (SN: 6/10/95, p. 367). H. influenzae relies on some 1,700 genes, while M. genitalium, the smallest known genome, has about 470.

Koonin notes that the two microorganisms represent branches of bacterial evolution that diverged at least 1.5 billion years ago. Yet the bacteria possess many genes that remain similar in DNA sequence and in function. Those conserved genes, 240 in total, are probably essential for cellular function, says Koonin.

That set of genes lacked some enzyme functions crucial to a cell, however. To fill the gaps, the researchers added 22 genes from M. genitalium's genome. (H.

influenzae has genes whose proteins perform similar functions as the proteins of these M. genitalium genes, but their DNA sequences do not appear to be related.) Finally, they eliminated six conserved genes that appeared to be either redundant or needed only to interact with the hosts of these particular bacteria.

Jack Maniloff, a microbiologist at the University of Rochester (N.Y.) Medical Center, cautions that the 256 genes identified by Mushegian and Koonin may bear little resemblance to the genetic repertoire of a presumed ancestral organism. Maniloff notes that such an ancestor, unlike the two modern bacteria, probably lived at high temperatures, had little oxygen available to it, and drew energy from sulfur.

Still, Maniloff suggests that seriously investigating the size of the minimal genome is in itself an important advance. "I'm pretty pleased our species can address the question. I think it marks a stage where we can gauge the essential components of a living cell."- J. Travis