Science Nerd Moment for Today: Recoding


There’s an interesting article in Nature today, discussing some recent research on how the protein-manufacturing mechanism inside our cells works.  But first, some background.

The cells of pretty much every life form on earth all work the same way: they are protein manufacturing machines. The DNA inside the cell is the instructions for how to generate proteins. The existence of specific proteins inside the cell “activate” parts of the DNA to generate new proteins, which then activate other parts of the DNA, and so on. There is a separate mechanism inside a cell that can pull certain proteins to one side of the cell or the other, so that when the cell divides each half contains a different collection of proteins, and from that point on different parts of their DNA get activated — that’s how we get cell differentiation.

Not only does every cell do this, but there is substantial evidence that every cell does this in almost exactly the same way — in particular, the mapping of DNA sequences to proteins is the same in every species.  So different species share the same protein manufacturing engine, but run it with different DNA sequences to produce a wide variety of results — in fact, all the biodiversity we see in the world.

Viruses are not actually alive: they are essentially free-floating DNA sequences packaged up in a way that allow them to get inside of cells and insert themselves into the cell’s own DNA so that the cell will generate copies of the virus which can then go on to infect other cells. The fact that every cell, across every life form, uses the same protein-generating machine enables viruses to spread not only between members of the same species, but sometimes across species (leading to diseases such as bird flu, and most recently MERS).

At least that’s how we thought it worked.  While there is substantial observational evidence that all forms of life used this same mechanism, all the way down to the same protein encoding, no one had gone looking to confirm that  this was in fact the case. Or more to the point, no one had gone looking for exceptions, until now. Which brings us to this newly-released research. The scientists reasoned that if there were exceptions, where in fact the machine had evolved to use a different coding scheme, it would probably happen in microscopic life forms first, since they are much simpler: more complex life would “break” more easily, or put another way, the number of simultaneous changes in a complex form of life that would need to happen in order to change the code and still keep everything running would make the odds of it happening astronomically high. An analogy would be to take an iPhone app and randomly change some parts of the code, with the result being an app that ran on Android devices: it could happen, just as 100 monkeys pounding on keyboards could write Shakespeare, but it’s extremely unlikely.

So they went looking at bacteria, and sure enough, they found lots of cases where it was happening.  In fact, their findings most likely underestimate the frequency of this happening, since they went looking for just one specific kind of recoding: places where the “stop” codon, the DNA sequence that marks the end of the instructions for a protein, was reinterpreted as something else. There are dozens of other possible recodings which no one has looked for yet.

Curiously, bacteria with recodings were overrepresented in humans, compared to other species. No one knows what that means, or why that happened. It’s a fertile area for research; someone recently pointed out to me that the number of bacteria in the human body far outnumber the number of actual human cells; from that point of view, each of us could be described more accurately as a collection of bacteria than as a collection of cells. I say that simply to justify the observation that bacteria are an essential part of human life, and we are just beginning to understand the depth of the role that they play.

So why is this all interesting? Beyond the insight into how evolution is moving life forward, it points to new ways to think about “biosecurity” — how we protect ourselves an our ecosystem from runaway diseases. This hold for both naturally-occurring ones, like major pandemics, as well as artificially-created ones. Bio-engineering is leading us into new territories, where scientists are learning how to create simple artificial life, as well as to make modifications to existing ones. Science fiction is full of warnings of new forms of life that run amok.

But take our previous example of viruses that jump between species. If the basic protein-coding scheme between species is incompatible, then the likelihood of a virus being able to jump between them is very low; again, just as an iPhone virus can’t jump to an Android device. That could end up being a key safety design point for artificially-designed life: enforcing changes in its protein coding mechanism to prevent cross-contamination.  There will always be viruses, and the researchers who worked on this study have already found viruses specific to the recoded bacteria they cataloged. But recoding may isolate those viruses to their specific species.  Or not: even if the virus can’t hijack a cell to make numerous copies of it, it might still make the cell a “carrier” and simply go along for the ride.





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