Their focus is on bacteria that live inside other organisms, both those that are harmful and those that are beneficial to their host.

Genomics -- the sequencing and study of entire genomes of organisms -- is opening new windows into the lives of these specialized microbes. By comparing the genomes of beneficial bacteria with those of harmful ones, researchers are beginning to unravel how harmfulness or beneficiality evolves.

In traditional models of evolution, organisms are thought to change slowly over time through small changes in their genes, or mutations. While this may hold true for eukaryotic (non-bacterial) organisms, many bacteria may evolve primarily by acquiring genes from each other, or by dropping whole genes that are no longer needed.

Bacteria can easily swap genes by direct transfer of genetic material from one cell to another, even between bacteria that are only distantly related. This well-known phenomenon allows harmful bacteria to react quickly to new host defenses, and to share their new counter-defenses with each other -- witness, for example, the rapid spread of antibiotic resistance among bacteria.

"If you want to move into a new environment, it's much easier to get a gene from someone else in that environment... than trying to evolve it yourself -- which is going to take a lot more time," explains Ochman.

A more recently discovered and less well-known aspect of genome evolution in bacteria is gene loss, in which entire chunks of the genome are deleted. "A region of a hundred genes or ten genes may have been lost [at a time]... these big deletions occur all the time," Ochman states.

Whereas gene acquisition can be beneficial, gene loss is usually catastrophic. However, in host-inhabiting bacteria, the protection of the host environment may allow the bacteria to survive such a loss.

"If you're a free-living organism, you lose a certain gene, if it's essential, you're dead. But if it's something that's not essential," for example a gene for the production of a nutrient you can get from your host, bacteria can keep living and reproducing after the loss, but they can never perform that function again. Further, because they are imprisoned within the host, they may have little opportunity to gain the genes back from other bacteria by swapping genes.

"Most people think that bacteria only have tiny genomes so they can replicate faster," Ochman says. Instead, a reduced genome may be a negative side effect in bacteria living as obligate insiders. Such bacteria have small populations, and because natural selection is weaker in small populations than in large ones, harmful mutations leading to gene loss can accumulate, whereas such mutations would be weeded out in a larger, free-living population.

"You're not getting smaller because it helps you replicate faster, you're getting smaller because things get knocked out, and are eroded away, due to your population structure," Ochman emphasizes.

These microbes with tiny genomes belong to large and ancient groups of bacteria consisting of only pathogens or symbionts, underlining that genome reduction in such circumstances is a one-way path.

"Once you're a symbiont, and you've deleted [large parts of] your genome, you're at a dead end -- you can't go backwards," Ochman points out.

"Bacteria evolve in a different manner than eukaryotes [all non-bacterial organisms]. Eukaryotes evolve by point mutations [changes in singe base-pairs in the DNA], whereas bacteria evolve by getting these large chunks of DNA. And they can get into a new niche then and they become new species.

"But... you can lose genes, [and] that make you into a new species also, because you can no longer go into that niche that you could previously get into. So we wanted to show that these big chunks of DNA, which are both gained and lost, can dictate bacterial speciation, and the lifestyle that the bacteria can have," Ochman says.

The ability of bacteria to evolve rapidly, by gaining and losing whole chunks of DNA, instead of by gradual genetic change, may perhaps be one of their keys to success. After all, bacteria have been around for 3.5 billion years, a good 2.5 billion years longer than any other group of organisms, and they show no signs of giving way to the latecomers. They must be doing something right. - By Margrit McIntosh

[Contact: Howard Ochman]

11-May-2001