Friday, January 27, 2006

Minimal genomes

All the information needed to make a cell is in a handful of genes for protein synthesis, some for DNA and RNA metabolism, a few for making the envelope, and a smattering of others.

The burning question is, which specific genes are essential for making a working cell? A number of techniques are used to arrive at estimates.

Knowledge of what constitutes a minimal genome could allow researchers to build new life forms from scratch. It could also help combat drug resistant bacteria, by allowing the development of antibiotics that target genes the bacteria just can't do without.

Interestingly enough, there seem to be a number of different "minimal gene sets" around.

About 80% of the approximately 250 genes found essential for B. subtilis are present in all bacteria that have a genome of "a decent size, about 2.5 to 3 megabases or above,"...

— Dusko Ehrlich of the National Institute for Agricultural Research (INRA) in France

In contrast, Salama's group has found surprisingly little overlap, only 11%, among the essential genomes of Helicobacter pylori and the other bacteria they examined, with 55% of the genes shared by only some species.

— Nina Salama of the Fred Hutchinson Cancer Research Center

So what do these differences mean?

"I think that reflects all these subtly different niches for which these different bacteria are adapted," [Salama] says.

So we may be seeing the descendants of different ancestral bacteria, each with its own set of essential genes.

Part of the problem involves defining just what "essential" means.

Ehrlich points out that essential genes really need to be defined by the conditions under which they were tested: "We used rich medium for our test. If we used different medium, many more genes would be required, because [the bacteria may] have to synthesize all the amino acids and vitamins."

and

Assays such as Rubin's screen for optimal growth in randomly mutagenized cultures. Thus, a mutation conveying drastically slower growth would probably be scored as lethal (because the bacteria harboring it would be out-competed), and the gene would be seen as essential.

So a gene that's essential in one environment becomes non-essential in an environment where essential nutrients are abundant. (For example, the ancestors of primates survived the loss of the ability to synthesize vitamin C.) And a mutation that conveys drastically slower growth is only "essential" for a bacteriium that has to compete with other fast-growing strains.

One of the challenges of abiogenesis (origin of life) research involves determining just what chemicals would have been available to the very first living things, and what roles they could play that are now being played by synthesized molecules today.

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