In a recent blog post, I claimed that nobody has yet tried to “evolve” Vibrio natriegens in the laboratory to make them grow even faster. But I was totally wrong, and it warrants a correction.
For context, V. natriegens is a microbe that doubles every 9.7 minutes in highly enriched growth media, or every ~30 minutes in more “minimal” media, with just some sugar and salt. In my recent blog, I explained that these cells divide faster than any other known organism because they make a large number of ribosomes quickly. (It has nothing to do with the time required to copy a genome):
“V. natriegens has at least a dozen ribosomal RNA operons, or gene clusters encoding ribosomal RNA molecules, in its genome… [Also,] these ribosome genes are located next to strong promoters, or genetic sequences that recruit RNA polymerase enzymes. In other words, Vibrio devotes more of its genome to ribosomal genes, and has also evolved a stronger start signal for those genes, meaning the cell makes ribosomal RNA much more frequently, and in higher numbers, than other microbes.”
At the end of the blog post, I proposed some experiments to make Vibrio natriegens grow even faster. Perhaps we could make its ribosomes smaller, such that each one takes less time to create. Or, alternatively:
“…we could take a more agnostic approach and just let evolution take its course, albeit in an accelerated way…Perhaps we could run a Richard Lenski-esque experiment, in which V. natriegens’ cells are grown in a robotic bioreactor and flooded with glucose every few hours…If we repeat this lots of times, some microbes may evolve to grow even faster… Or maybe not; V. natriegens may already be quite close to the theoretical cell division time limit. These experiments haven’t been done yet.”
This last claim — that nobody has yet done these experiments — was totally wrong, as Adam Feist, bioengineer at UC San Diego, explained to me by email. Feist is a co-author on two studies that have done basically this exact experiment!
In one study, they used an automated laboratory evolution (ALE) robot to evolve E. coli cells to grow faster. Their goal was to see whether E. coli could grow as fast as V. natriegens. (Answer: No.) In a second study, they did much the same with V. natriegens to see if they could “break” its speed limit. (Answer: No.)
For the first study, the researchers took six different E. coli strains, including BL21, K-12 MG1655, Crooks, and others. They grew each strain in three triplicate flasks, filled with growth media containing just a minimal amount of sugar and salts, and incubated them at 37°C. Every time the cells reached a certain density, they transferred a tiny amount of cells into a fresh flask with the same exact conditions. And they repeated this again and again for 900 generations of cell growth.
The beauty of this experiment is two-fold: First, it’s super simple and easy to replicate. Every time cells are transferred into a fresh flask, microbes evolve to grow faster such that they can take over the nutrients in that flask. So this is artificial selection in a tube. And second, they froze the cells at regular intervals so they could sequence them, measure their gene expression, and so on to really figure out how the cells were evolving. After 900 generations, all six strains grew faster than they started. But none of them grew as fast as V. natriegens.
So the conclusion is clear: V. natriegens is probably close to its theoretical speed limit already, and evolution — even when accelerated in the lab — hasn’t been able to push it further. Thanks to Adam Feist for the correction.