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Gene networks: evolved not designed

This week’s paper, “Evolvability and hierarchy in rewired bacterial gene networks?, was suggested by Joel Lopez.

Randomly changing parts in a machine often breaks it. “Intelligent design? nuts claim this is also true of living things and that this is somehow evidence for design. The argument is nonsense – just because we had distant ancestors small enough that they didn’t need lungs doesn’t mean we can survive without them -- but is the claim even true? If a genetic change is big enough to have some effect, is it likely to be lethal? Or do many mutations preserve basic functions, just increasing or decreasing fitness (survival and reproduction) under particular circumstances?

Mark Isalan and colleagues randomly switched promoters that control production of transcription factors in bacteria. Promoters are the sections of DNA molecules that, instead of being transcribed into RNA and then translated into proteins themselves, control transcription of nearby DNA sections. Transcription factors are proteins that bind to and control promoters, so they are among the most important control signals in cells.

Linking the DNA coding for a transcription factor to a random promoter would be equivalent to changing an army codebook, so that “retreat? is translated into “destroy the bridge,? for example. So it may seem surprising that 95% of the randomly reorganized bacteria, including some with changed regulation of genes that themselves regulate hundreds of other genes, appeared to grow normally.

One explanation that occurred to me after reading the abstract of the paper was that maybe the added promoter-gene combinations were somehow defective, not doing anything. But each combination also included a fluorescent protein gene after the transcription factor. The modified bacteria made the fluorescent protein, so they presumably made the transcription factor as well. Changes expected to result in negative feedback gave similar fluorescent protein levels to those expected to give positive feedback, however. This suggests that other feedback loops were limiting the effects of those added by the researchers. (Similarly, an army unit receiving a strange order due to a codebook error might ask for independent confirmation first. Or so I assume.)

This paper reminds me of an earlier experiment in which researchers made mice without myoglobin, previously thought to be essential for oxygen supply in muscles. Other aspects of their physiology apparently filled the gap.

Nonlethal genetic changes are the raw material for evolution, so the authors tested their genetically modified strains to see whether there were any conditions under which they were more successful than the original strain. Twelve strains outgrew the original in liquid culture, apparently because they didn’t make flagella (propellers that are expensive to make and only useful if there’s somewhere better to swim to). Some strains also did better at high temperature than the original.

Maybe our earliest single-cell ancestors were so simple that most genetic changes would be lethal. But humans, mice, and the bacteria used in these experiments are the products of billions of years of evolution. Lineages that were killed by every little mutation died out, while those with enough redundancy to tolerate most mutations survived and continued to evolve.


The studies that are possible these days are just mind blowing.

I wonder if they plan to keep on culturing the mutated strains. It would be interesting to see how their evolution diverges from that of the original strain.

I don't think they are planning long term evolutionary experiments with these strains. I am no longer in that lab but the idea was not being discussed at the time at least. Still, one of the main conclusions was that these changes are mostly neutral to the cell so I guess the assumption would be that it would influence their future evolutionary trajectories that much. It is an interesting question but the most interesting finding (different trajectories) could occur only for some very particular environment of sets of events that could be hard to find.

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