Transfer Molecules

When Caleb merged with an alt-Caleb, it added two more amino acids to its repertoire, and also started reading genetic chains that were built from four amino acids. That gave it a big advantage over the older Calebs, which were confined to just two amino acids and two chain molecules. If you look close at the chain during transcription, you'll notice that Caleb was now using two entirely different mechanisms to select the next amino acid for a protein. For some amino acids it uses the original Fred style of conformation changes, along with a jiggle to the next chain molecule. In other cases it uses 'alternating Freds' to bring in a different amino acid when the chain molecule changes from a Sofia to an alt-Sofia or vice versa. Alternating Freds Considering this system on a structural level, it appears that alternating Freds might be a much more reliable way to add amino acids, as opposed to the conformational changes in the original Fred. For one thing, using multiple Freds is much less likely to backslide or skip a chain element, since the Fred-to-Fred linkage can 'walk' along the chain in a controlled manner. That seems much more reliable than the random 'jiggle' that we described for the earliest Fred translations. Fred was also a rather overloaded protein-- it was matching a chain, shifting its conformation, binding an amino acid and catalyzing the amino acid polymerization, all in a single molecule. Its evolution could probably proceed much faster if it had fewer functions to manage. Assisted Transcriptions So let's imagine the introduction of a mutant version of Fred, which has lost its amino-acid binding and chain-reading properties, but which still has its protein-catalyzing active group, and the ability to ratchet along a genetic chain. We'll call it a Fatcat . (short for Fred Assisting Transcription CATalyst). When this new protein connected to a genetic chain, it wouldn't be able to transcribe proteins directly. However it would be able to manage the transcription process by using multiple copies of Fred. The new system might work as follows: 1. Fatcat binds to the chain, and attracts a Fred. Fred's elbow matches to the first element of the backbone chain, just like it always has. Its knee accepts the first amino acid just like usual, perhaps with some assistance from Fatcat. Fred would attract a specific amino acid just like usual, and we'd have the start of a protein. 2. Now Fatcat ratchets along the chain by one molecule. It also ejects the first Fred and accepts a second one which matches the next backbone chain molecule. We could still use an 'old Fred' that would go through a conformational change, but we could also use a simpler 'new Fred' that is designed to carry just one amino acid (more about that later). 3. Fatcat binds the two amino acids, then ejects the second Fred. An alt-Fred diffuses in and adds a third amino acid. Again, note that this could be an original alt-Fred, or it could be a simpler new alt-Fred that doesn't need to fuss with conformational changes or catalytic activity. 4. Fatcat binds the third amino acid to the polypeptide chain, then eject the alt-Fred and accepts another one. The original alt-Fred could still work here after shifting conformation, but the quicker and easier choice is to use a simpler new Fred that binds to just one amino acid. 5 The process continues, one Fred at a time, and eventually we have a polypeptide chain built from four different amino acids. Separation of Functions With this new system, Fred really doesn't need to change its conformation at all-- it just needs a recognition site at the elbow to match up with the chain, and an amino-acid binding site at the knee. With no need to select different amino acids or to catalyze amino acid polymerization, it could be simpler and smaller, and could more easily evolve into individual carriers for different amino acids . Our new Fatcat protein takes over the positioning and catalytic functions that were formerly handled by Fred. Since Fatcat doesn't need to recognize chain molecules or bind to proteins, it also has an easier time evolving a more efficient structure. Its only functions are to manage Fred placement, and catalyze the linking of amino acids. In other words, with Fatcat managing the positioning and catalytic functions, Fred can become a passive carrier for an amino acid. In addition, we can just have several separate versions of Fred, each designed to carry a specific amino acid, rather than a single, bendy Fred that tries to distinguish between multiple amino acids. Transfer Evolution How could the four-Fred carrier system have evolved from the earlier Fred system? Plain old original Fred could have become a carrier for one of the four amino acids just fine-- whichever one matched the knee end when Fred was in its normal, relaxed state. To be a perfect carrier, it just needed to lose its flexibility, and freeze into that position. Fred could also have evolved into a passive carrier for the second amino acid quite simply-- all it needed to do was to permanently lock into its second conformational state (probably not a difficult sequence change). Once that happened, it would naturally bind to the proper amino acid. Alt-Fred could also have evolved easily into carriers for the other two amino acids, via mutant forms that were permanently locked into each of its two original conformations, the same way as we have described for Fred. Fatcat Timing The system of 'alternating Freds' is so much more efficient than the old jiggle system, that one might wonder why it didn't just start out that way from the very beginning. Why have Fred do everything? Well, here's the problem-- the 'alternating Freds' system requires at least two different proteins, which means that two proteins and two chains to code for them had to get together at the same time. That is a zillion times less likely than the simple Fred and Sofia meeting that we described a while back. Even though the original Fred was rather mediocre, it did work well enough to get things rolling. Of course, Fatcat may have appeared soon after the appearance of Fred and Roscoe. Chemically speaking, it was similar enough to Fred that it could have easily formed from a bad copy of Sofia, and it does provide a much more reliable ratchet mechanism than Fred could have done on its own. It's quite possible that some of our genetic story to date should include Fred and Fatcat working together. However, it really doesn't change anything important, in the earlier molecular evolution. Pre-Loading One major fringe benefit of this new passive-carrier system for protein transcription, is that it offered a potentially huge increase in both speed and reliability. Since each 'new Fred' always carries the same protein, it can 'pre-load' with a specific amino acid even before it reached the chain. That removes one 'wait state' from the synthetic pathway, and greatly increases the speed of the transcription and protein formation. Pre-loading would also increase transcription accuracy, since the amino acid can bond to Fred in some other location, where Fred can be loaded via an enzyme. The passive-carrier Fred might even link temporarily to the enzyme that first creates its amino acid, and grab it fresh off the assembly line. Alternating Roscoes Being able to transcribe proteins containing four different amino acids was a potentially huge improvement for Caleb. But of course, it would only work if it was also possible to replicate those four-molecule genes reliably. Fortunately, once Fatcat came on the scene, it would have been an easy jump to make an equal improvement in the replication process, using a slight variation of Fatcat that we'll call Ratcat (short for Roscoe Assisting Transcription CATalyst). Ratcat would work like this: 1. Ratcat binds to the chain and attracts a Roscoe. Roscoe's elbow matches to the first element of the genetic chain, just like it always has. Its knee accepts the first chain molecule just like usual, perhaps with some assistance from Ratcat, to speed things along. Roscoe would attract a specific chain molecule just like usual, and we'd have the start of a new genetic chain. 2. Now Ratcat ejects the first Roscoe, and accepts a second one which matches the next backbone chain molecule. Just as with the Fred transcription, we can still use an old Roscoe that would go through a conformational change, or we can switch to a simpler new Roscoe with a fixed orientation and a fixed binding site for just one chain molecule. 3. Ratcat binds the two chain molecules, then ejects the second Roscoe. An alt-Roscoe diffuses in and adds a third chain molecule. Again, note that this could be an original alt-Roscoe, or it could be a simpler new alt-Roscoe that doesn't need to fuss with conformational changes or catalytic activity. 4. Ratcat binds the third chain molecule to the new genetic chain, then eject the alt-Roscoe and accepts another one. The original alt-Roscoe could still work here after shifting conformation, but the quicker and easier choice is to use a simpler new Roscoe that binds to just one chain molecule. 5 The process continues, one separate Roscoe at a time, and eventually we have a new genetic chain built from four different molecules. Improved Proteins Back in the early days of Fred 1.0 and Roscoe 1.0, we had to accept a certain amount of flakiness in replications and transcriptions. After all, Fred had to be a very short and simple protein, to have any chance at all of appearing from pure random soup. But now life has evolved quite a bit, and we can expect that the latest versions of Fred, Roscoe, Fatcat and Ratcat can be quite a bit longer, more complicated, and more effective at what they do. We're still drawing them as the same simple structures, partly out of laziness, and partly to avoid cluttering up the diagrams with huge proteins. But it's reasonable to suppose that all of Caleb's molecules would be gradually evolving into better forms, as we proceed through this story. Previous Home Next