Fred & Sofia FAQ

Before we move on, here is more about Fred and Sofia, in Q&A format. How big was Fred? Fred had to be as small as possible in order to have much chance of being created twice (once as a protein and once as a genetic chain). On the other hand, it also needs to contain at least two chemically active groups, and a section that could flop into two different conformations. Possibly 20 to 50 amino acids? What was Fred made of? Fred needed to manage very low-energy reactions, since it didn't have an outside source of energy. Most likely it did that by fiddling with the repulsion between oily, hydrophobic substances and water. Because of that, the odds are extremely good that it was built from one hydrophobic (oily) amino acid, and one polar, water-loving amino acid. Fred probably contained fairly small, simple molecules, simply because they were likely to be more common. A couple of good candidates for the hydrophobic half of Fred would be leucine or valine . Fred's polar half was probably also a smallish molecule, but one with a polar side branch that was attracted to water molecules. Among modern amino acids, aspartate or glutamate might be good candidates. One of the positively charged amino acids like lysine might also be possible, or a neutral-but-polar amino acid like serine. With hydrophobic and polar areas in just the right places, Fred could function at simple tasks like shoving around amino acids, or sensing chain molecules. There are a few amino acids that contain aromatic rings, but it seems unlikely that Fred would have started out containing one of those. Chemically speaking, they could have served as the hydrophobic portion of Fred. However, the aromatic amino acids are rather large and rigid, and probably would have prevented Fred from folding into the compact and flexible shapes that it needed for proper functioning. What was Sofia made of? Sofia was almost certainly built from molecules that contained aromatic rings, since they are flat molecules that 'stack' nicely into a rigid chain. The purines and pyrimidines are good candidates, and it seems reasonable to guess that Sofia might have been built from one of each. Sofia may have contained one or two of the modern chain molecules-- adenine, cysteine, guanine, tyrosine, or uracil. Or it may have used some entirely different chain molecules that just happened to be present in the local puddle. The pyrimidines have a single ring, while the purines have a double one. That creates a big enough difference that Fred would have no problem distinguishing between them. Of course, a Sofia built from two different purines, or two different pyrimidines could have also worked. In that case, Fred would have 'read' them by shifting its elbow because of differences in the location of charges or side chains on each type of Sofia molecule. Sofia's chain molecules may have been linked by ribose sugars and phosphates, similar to modern RNA and DNA. They may also have bonded in some entirely different way. How did Fred's elbow work? Fred's elbow needed to bind to a aromatic chain. To accomplish that, it probably contained a sequence of the right types of amino acids to match up with the polar and hydrophobic portions sticking out from the perimeter of each chain molecule. In our illustrations, we have Fred sliding along the bottom of Sofia, so it's easy to see how it works. However, in fact, Fred's elbow probably wrapped around the chain so it could stay attached, and so it could more easily 'sense' the shape of each Sofia molecule. Fred might have had a groove where Sofia could fit, or a hole that Sofia would slide through. The elbow needed to distinguish between two different chain molecules as it moved along the chain, and shift the conformation of the knee depending on which molecule it met. It may have done that by size, or by using hydrogen bonding to interact with polar portions of the chain. There may have been a couple of polar amino acids that bound to the polar portion of the chain molecules, shifting their position depending on the side groups in each chain molecule. That shift could easily have transferred to the knee via a simple movement in the connecting amino acids. How did Fred's knee work? Fred's knee needed to accept either of two amino acids, and then either hold it in place (if the first molecule in a polypeptide) or bind it to an amino acid in a chain already connected to Fred. To attract amino acids in general, it probably used a couple of polar molecules to attract the charged portion of the amino acids. The acceptance area probably was shaped so molecules of about the right size could fit in. The knee could have distinguished between amino acids by their polarity (perhaps by shifting a polar group in or out of the acceptance area) or by their size (by changing the size of the acceptance area). Most likely a portion of the knee bound to the incoming amino acid, and then positioned its N-terminal (amino) group with the C-terminal (acid) group in the previous amino acid. As long as the local solution was concentrated enough, the two amino acids would have connected covalently, with the loss of one water molecule. How did Fred move along the chain in one direction? We've talked about Fred 'jiggling' down the chain and reading each molecule in the chain. Is that reasonable? Maybe. By sheer random diffusion, Fred would most likely stay in the same place indefinitely, and just keep adding more of the same amino acid. Or it might jiggle just as easily in the backwards direction as forward. However, it is likely that the addition of a new amino acid at Fred's knee would affect the amino acid structure in between the elbow and the knee. That might shift the conformation a little, and perhaps shove out a polar amino acid on the back side of the elbow, repelling from the hydrophobic part of the aromatic chain, and propelling it down the chain. Alternatively, it might shove out a hydrophobic amino acid on the front side and attract its way forward. Such a 'ratchet' mechanism might be reliable enough to move the first version of Fred in one direction, and allow a reasonable degree of transcription accuracy. How long would it have taken for Fred to appear? We can do some very ballpark math, and get some kind of extremely vague guess at the odds for a Fred/Sofia meeting. If Fred is a 20-molecule polypeptide built from two amino acids, and if there is only one unique sequence that works, then we can expect to see one Fred in every 220 polypeptides of that size, or about one in a million. In a puddle with a concentration of two amino acids and with some condensing catalysts or templates, it might be reasonable to expect that a few long-chain amino acids would form every day. That would mean 1,000 polypeptides formed per year, which would mean a Fred might be produced about once every 1,000 years, on average. How long would it have taken for Sofia to appear? The probability calculations for Sofia are almost identical. If Sofia is a 20-base chain built from two components, and if there is only one unique sequence that works, then we can expect to see one Sofia in every 220 chains, or about one in a million. If catalysts or templates in a shoreline puddle assembled a few chains that size every day, it might mean 1,000 chains formed per year, which would mean a Sofia might also be produced about once every 1,000 years on average. Multiply those odds together in a suitable puddle, and it means that a Sofia and a Fred might meet up once per million years (assuming that the molecules themselves stick around for about a year, on average). That is a long dry spell in the dating game, but not bad at all on a geological time scale. The 'window' in which life appeared is at least a couple hundred millions of years long. What are the odds for the Fred/Sofia puddle? How many puddles in the prebiotic Earth would have had the right concentrations of just two amino acids and two chain molecules? That is an even tougher question to answer. It depends on the overall frequency of supercatalysts, or crystals of organic compounds in the 'concentrating' pools above the high tide line. It also depends on how fast the amino acids and chain molecules diffused or splashed, how fast they were formed, and how fast they were destroyed. Even the 'roughness' of the prebiotic shorelines has an impact, since some rocks seem to produce more shoreline puddles than others. There may have been one puddle with the right conditions to produce a Fred and a Sofia, or there might have been billions. Any chance of finding Fred today? That seems extremely unlikely. Because Fred was built from just two amino acids, it was never as efficient as a modern protein, which has a 'toolbox' of 20 different amino acids to choose from. So it seems likely that Fred would have quickly been replaced by better proteins, during later evolutionary stages. If there is any trace of Fred, it probably would be in a small portion of some modern protein. Any length of protein that is built from just two amino acids would be a candidate. Any chance of finding a fossil Fred? It's very unlikely than any Fred or Sofia fragments will ever be found in the fossil record. Not only would they need to survive 4 billion years of geological activity, but they also needed to get past a few billion years of biological activity that would happily use them as food. In fact, there probably weren't that many Freds and Sofias in the first place. The odds are good that they evolved fairly quickly into more sophisticated life forms, before they managed to build up large populations of their very earliest stages. Any chance of synthesizing Fred? It would be an extremely interesting project to assay short chains built from just two amino acids, to see if Fred could be duplicated. Without knowing which two amino acids it was built from, there would be about 380 million choices to consider (assuming it was twenty molecules long, the total permutations would be 220 for each pair, times 20 x 19 combinations of amino acid pairs). However, a good guess at the initial amino acids would drop the choices down to 220, or about one million. Of course, Fred may have been built from amino acids other than the twenty currently synthesized by living organisms today, or possibly even from some other compounds. Those numbers make it unlikely that Fred would ever be found from a search of all possible short polypeptides, but there may be other ways to 'reverse engineer' its structure from its necessary physical properties. Protein Transcription More About Fred Alternate Freds