January 21, 2008

Lucky Choices

Posted by Eric at 7:30 am | Category: Biology, Literature

There’s an interesting article in Genetics on the luckiness of biology’s initial choice of bacteria to study. One of the most common bacterial types that molecular biologists studied back in the mid-20th century was E. coli K12. K12 was used a lot because it harbored a dormant λ virus (allowing the discovery of one of the most elegant genetic switches ever found), an F+ plasmid, and many suppressors of amber mutants (which I mentioned before).

All three of these features of K12 were extraordinarily important to the development of modern molecular biology, including the nature of the genetic code, tools for understanding gene regulation, fundamental mechanisms of transcription and translation, the circular nature of the bacterial chromosome, the mechanisms of transposition, the nature of recombination, and so on.

The paper talks in particular about amber mutation suppressors. Apparently strain K12, back when Edward Tatum first established it, had somehow acquired an amber nonsense mutation in rpoS, which codes for the RNA polymerase σS sigma factor needed for survival in stationary phase (i.e. semi-starvation and crowding phase). Lab strains often hit stationary phase when grown on plates, which would lead to a positive selection for amber suppressors. Thus, K12 acquired a large number of amber suppressors, leading to the discovery and utilization of a large number of conditional and conditionally lethal mutations!

Amazing how much biology has been discovered due to sheer chance…

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2 Responses to “Lucky Choices”

  1. Alex Says:
    January 21st, 2008 at 8:36 am

    You didn’t talk about whether other choices would have been more or equally fruitful–is it really the case that these discovered features are rare in other bacteria? Is it possible that we’re actually getting only a very small view of the possibilities because E. Coli was a bad choice with only a small number of interesting features?

  2. Eric Says:
    January 21st, 2008 at 9:29 am

    There are other model organisms that biologists have used, including salmonella, B. subtilis, and Caulobactor crescentus, to mention three other very commonly studied bacteria, and there are plenty of other eukaryotic organisms that were studied back in the day, especially yeast, fruit flies, and nematodes.

    I think E. coli K12 was more fortuitous than limiting, because it happened to have the right mutations to make genetic studies and biochemical studies very easy. It grows extraordinarily fast in the lab, and requires only a limited amount of sterility to prevent contamination. It can also be grown in liquid or on agar “plates”, which means that they can be grown in both huge amounts as well as in colonies formed from each individual bacterium, making quantitative study a lot easier. And E. coli has plenty of bacteriophages, that allow for the ease of manipulating DNA back before recombinant DNA technology was mature. Finally, E. coli also has interesting chemotaxis and motility, which made it a great model organism for studies of flagellar movement, sensory systems, and signaling.

    I think ultimately these discoveries would have been made in other bacteria, perhaps, but some of them (such as caulobactor) certainly grow much slower (which would make screening millions of colonies difficult) and have a much more complicated life cycle than E. coli, which is about as uniform and elemental as one can get in bacteria without being too boring and limiting. Even though other biologists were working in other model organisms, the fact that a huge portion of the molecular biology was worked out much faster in E. coli is very telling about its power.

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