First Protein Transcription |
Once upon a time, on a planet right here in our own galaxy, there was a puddle on the shoreline of a primitive sea. It filled a depression in a rugged and rocky place, up above the high tide line. For centuries, sea water splashed into it at each high tide, and then centuries of evaporation filled it with salt crystals, along with a few tarry blobs, films, crystals and membranes of condensed organic matter. You might think of it as primordial soup that had evaporated into primordial slime, or primordial jerky, at least during dry spells (for more about the soup, see Appendix 1). In fact, the whole neighborhood was that way, with every crack, cranny and crevasse filled with pools and puddles of salt water or evaporated salt, and various sorts of condensed organic goo. The tides rolled in three times a day , and splashed sea water into the puddle and its neighbors. Then the tides rolled out, and left it all to bake and dry in the sun (for more about the puddles and the concentration process, see Appendix 2). It was not unlike, say, the coast of California or Maine. Except that it was four billion years ago, give or take a couple of hundred million, and none of that organic stuff was alive. Instead, it was just a mix of random organic chemicals that had flown in by comet over the past billion years, or that had synthesized on Earth via various natural processes. This particular neighborhood was a wee bit unusual, since it had experienced some interesting chemistry history that produced a high concentration of a few small, organic compounds. That concentration may have resulted from simple crystallization of a few organic chemicals. Once a 'seed crystal' formed, it would have grown, bit by bit, as new soup washed into the local puddle and then evaporated . There may have been a few organic crystals in the neighborhood, right from the beginning, formed in interstellar space and then brought in as part of some cometary debris, or washed in after forming in some other location on Earth. Or the concentrations may have happened because some of the condensed bits of organic material were catalysts-- which means they could speed up the formation of specific chemicals, when presented with the right raw materials. In fact, in this particular neighborhood, there may have been several supercatalysts-- clusters of catalysts that were positioned just right so they produced a series of chemical reactions, much like a 'chemical factory'. Each of those catalytic clusters would have taken common raw materials, and created high concentrations of a specific organic chemical (for more about early catalysis, see Appendix 3). The Proteins For whatever reason, in this particular puddle there happened to be large quantities of two different amino acids. An amino acid is a fairly small molecule that is chemically stable, and that has a very interesting property. Each amino acid has both a positive (amino) end and a negative (acid) end. Two amino acids will attract each other, positive to negative. With the right catalyst or in a very concentrated solution, the two molecules will then merge into a larger bipeptide, with the loss of one water molecule. More amino acids can join at the two ends of the bipeptide, eventually creating a much longer chain-- called a polypeptide, or a protein, depending on its size.
In our special neighborhood, it's likely that one of those amino acid molecules had a bit of an electrical charge in its side chain, which gave it an affinity for water. We'll call it the polar one. The other was probably an oily character that avoided water like it was, well, water. We'll call it the hydrophobic one. Their interactions were pretty much like salad dressing made from oil and vinegar, only on a much teensier scale. During wet spells and very high tides, some of these two local amino acids dissolved, and washed out into neighboring puddles and pools that were within splashing distance of the source. During dry spells, they linked up into polymers, eventually creating many random protein chains that were dozens of molecules long. The Aromatic Chains This special neighborhood also included a high concentration of two other organic chemicals. These molecules had flat 'aromatic' rings built from carbon and nitrogen, and surrounded by a whirling cloud of free-floating pi electrons. They may have been purines or pyrimidines (shown below), or they may have been some related molecule.
The ring portion of these molecules were hydrophobic, while the edges were polar. In a water solution, that means that the hydrophobic rings would attract each other, then link up into moderately rigid chains, stacked up with the rings parallel, much like a pile of coins. The chains may have had some sort of chemical 'backbone' to connect each molecule, or they may have relied on simple hydrophobic repulsion to stay together. Thanks to the natural clumpability of the two molecules, there were many short, aromatic chains in the neighborhood, each with a random sequence that might have been dozens of molecules long. The Laboratory The earliest part of our story takes place in some tiny puddle on a rocky shoreline, slightly above the high tide line. The teensy bit of water between two sand grains would be sufficient space for all this molecular drama to occur (we'll call it a micro-puddle). At each high tide, splashing waves sent gobs and droplets of dilute primordial soup flying into the air. They'd land on the rocks, and then flow from puddle to puddle, bringing in new raw materials, dissolving portions of the organic materials that had previously condensed in the area, and rearranging the contents of each small pocket and pool. Any local catalysts or supercatalysts might create a few new molecules from the incoming raw materials, then plain old gravity flow and wave splash would send them off to nearby pools and puddles. At each low tide, everything baked, concentrated, polymerized and crystallized in the sun and wind. Then the tides rolled in again, and brought further change. The whole system was not unlike a demented chemical factory, with assembly lines set up completely at random, acting at the whim of whichever way the waves splashed each day. All that blobular 'machinery' might have continued for many millennia, producing a local concentration of 'interesting' molecules that had absolutely nothing to do with life. However, during one dark and stormy night, a rugged and handsome polypeptide, and a perky and vivacious aromatic chain, both happened to wash into one very special micropuddle. The stage is set for our first molecular drama, and it's time to meet the actors now. It all began with two short polymers. One was a polypeptide that we'll call Fred (our First REplicating Device), and the other was an aromatic chain that we'll call Sofia (Sequence Of Fred InformAtion). A Closer Look at Fred Fred was a dapper and relatively short polypeptide (possibly 20 or 30 amino acids in length). It was shaped just exactly right so it had two functional groups, which we'll call its elbow and its knee. In this illustration, we represent each amino acid as a circle, and we include the side chains for a few of the amino acids that are located at the elbow and knee.
Fred's elbow is at the top. It happens to have just the right chemical shape so it fits very closely around a single molecule of an aromatic chain. It probably wrapped around the chain, partly or completely, but to make the drawings clearer we'll just have it ride along the bottom of the chain. Fred's knee is at the bottom. It is a catalytically active group that is able to attract two amino acids, and merge them together via a dehydration reaction. Fred has no source of outside energy, so it can only do that in a salty, concentrated solution, where the energy equation is in favor of polymers. But fortunately for us all, that is exactly where it happens to be. Fred also contains a moveable linkage between the two groups (the shaded section in the illustration below). When there is one type of aromatic molecule at the elbow, it shifts the Fred molecule into one position, which puts the knee into an orientation where it will attract only a hydrophobic, oily amino acid.
When there is a different molecule at the elbow, it shifts the position of the chain, which in turn 'snaps' Fred's knee into a slightly different position. In this new conformation, Fred only attracts a polar, water-loving amino acid. Small polypeptides are easily capable of this kind of conformational shifting and enzymatic activity, so we can't say that Fred was particularly uncommon. It was just very, very lucky, once it met the chain of its dreams. A Closer Look at Sofia Sofia, the aromatic chain, is our other starring molecule. It is a relatively short chain (possibly 20 or 30 molecules in length) assembled from two different aromatic molecules. Each oval in the illustration below represents one chain molecule. Some of the aromatic chain molecules are a bit bigger than the others, so we draw them with an extra circle beneath the main part of the molecule.
Sofia was originally condensed randomly from the two aromatic chain molecules that were common in the local puddle. Nothing special, just a random sequence of two different molecules, assembled into a linear chain by simple hydrophobic attraction. The two molecules may have been a purine and a pyrimidine (similar to modern RNA and DNA), or they could also have been just about anything else. Right now we don't need to be too fussy about the chemical composition of our starring molecules. They just need to be different enough from each other, and capable of forming long polymers. Sofia has the potential to be a very tough and resourceful molecule, and later on we'll see some of the chemical tricks it can do. But right now, none of those skills are important, and we will just let it be a passive participant in the drama to follow. Fred and Sofia were nothing special on their own. But once they splashed into the same puddle and diffused close together, they did something that would literally change the world. Fred's elbow bonded to one of the chain molecules in Sofia, and then Fred gradually moved along Sofia's sequence of molecules, and 'read' it. Meanwhile, Fred's catalytic end used that information to build an exact duplicate of itself. We'll call it Fred Junior. It was the very first step in the very long process of forming life. The first protein transcription had begun. Fred and Sofia in Pictures Let's take a closer look at Fred and Sofia's first meeting, step by step, since what we just described is extremely important. It's the very first courtship dance! For raw materials, we are using two 'modern' amino acids-- leucine (hydrophobic, L) and glutamate (polar, E). Of course, Fred may have been built from entirely different amino acids, perhaps ones that are not even found in current living organisms. Here is the very first protein transcription, step by step: 1. At the beginning, Fred's elbow (at the top) attaches to the first element of the Sofia aromatic chain.
2. A hydrophobic group in the knee (bottom) attracts a hydrophobic amino acid.
3. That jiggles Fred, which slides over to the next molecule in the aromatic chain. Fred's elbow attracts another hydrophobic amino acid. Because it's in a very concentrated solution, the two amino acids bind together, with the loss of one water molecule.
4. Another day, another amino acid.
5. Fred jiggles onto the fourth chain molecule, which is different from the first three. It forces Fred's elbow into a slightly different position, which pushes on the knee and forces that into a slightly different position. The result is that Fred now has a polar group sticking out at the knee. That attracts a different type of amino acid, which binds to the new chain.
6. A few more jiggles, and we're further along the chain, with a growing polypeptide at the knee end.
7. Fred continues, reading each molecule in Sofia, and using it to determine the structure of the embryonic polypeptide:
8. After a few more of the same, Fred reaches the end of the chain, and detaches. It also detaches from the new polypeptide it has created.
9. Amino acid chains are very flexible, and they usually like to fold up into compact blobs. So each of those amino acids responds to attractions and repulsions from the surrounding water and the other molecules in the chain, and the entire polypeptide folds up into a specific globular structure…
which just happens to be another Fred. Welcome to Baby Fred Junior! Awww, ain't it cute? Second Replication Of course, Fred and Fred Junior were still sitting very close to Sofia, and sooner or later one of them probably succumbed to temptation, diffused back to the beginning of the chain, and transcribed another copy. Then there were even more Freds, and even higher odds that a Fred would manage to transcribe still another Fred. By the end of the tidal cycle, the result would have been a puddle o' Freds, with many of the local amino acids assembled into tiny but potent Fred-making machines. Survival of the Fittest So then better and better Freds evolved, right? Well, no. Not yet. There is only one Sofia, and whenever a Fred hooks up with it, the result will always be a plain old Fred. There may be mutant Freds produced by erroneous transcriptions, that do a better job of transcribing Sofia. But whenever a more efficient new Fred happens to roll off the Sofia assembly line, it has absolutely no way to pass along the improvement. When that better Fred connects to Sofia, all it will do is reel off a bunch of same old original Freds (though in an improved and more efficient way). There is still more that needs to happen, before we can have any real evolution of our first life-like chemicals. Suicidal Freds It's important to keep in mind that life really hasn't begun yet. All we have is the most primitive of self-replications, and there is no such thing as 'natural selection' yet. That means that Fred and Sofia have absolutely no instinct or skills for survival and reproduction. Fred would be just as happy to attach to a different aromatic chain, and use it to create a different enzyme that would slice Freds or Sofias into small pieces . For the sake of story telling we won't have this Fred do that , but it's important to remember that for quite a while yet, any 'selective pressure' on Fred or its progeny must happen strictly in the random, chemical sense. It will take several more chapters before we start seeing any real natural selection and evolution. Precarious Life In fact, you might say that this very early form of self replication was totally hanging onto to life by a thread. It wasn't very good at doing much of anything that would help it to survive. If the local puddle dried up too much, Fred would polymerize into a FredFredFred, which would just be an amorphous blob that wouldn't do anything interesting. If the puddle got too dilute, Freds would tend to gain a water molecule and break up into Frs and eds that would also be useless. Introduce a new amino acid to the local molecular mix, and Fred was doomed-- it would produce Frzd and Fzed and Frzz, and collapse into chaos. Zap Sofia with an energetic photon, and it's end of story. And let's not even think about comet impacts, volcanic events, or massive storms. There were many, many ways for Fred and Sofia to simply return to random soup, and it's quite likely that is what happened in many puddles, with many previous Freds and Sofias. This couple went a little further, but it took some luck! The Diffusion of Fred Back in the 'home puddle', right now we have a single Sofia in a puddle with a local concentration of Freds, created by other Freds whenever they happened to hook up with Sofia. At each high tide or storm there might be a few Freds diffusing out into the outside world, but those Freds would be totally unable to do anything interesting, when they got there. At the moment, we have a very fragile, barely self-replicating system that can't survive the loss of Sofia, or even a drastic change in the local chemical conditions. Some of the traveling Freds might meet up with other aromatic chains, and form other polypeptide chains (perhaps made from completely different amino acids). They would be interesting new polypeptides, but they wouldn't be Freds, and they wouldn't contribute anything to our story of life. More things need to happen before Fred can be anything more than a temporary, chemical curiosity. And it's time to look at the next of those steps, now.
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