Evolution of DNA - Protein Transcription
First Protein Transcription
First Genetic Replication
First Feedback
Puddle Evolution
First Dispersal & Evolution
First Parasite
First Organism
First Cell Metabolism
First Self-Sufficiency
Aromatic Assistants
First Assimilation
First Transfer Molecules
Eight Molecule Life
Complementary Base Pairs
Energy Sources
Conquering the Oceans
First Cells
Cellular Explosion
Gene Regulation
First DNA
Wider Reading Frames
Complementary Triplets
Cellular Scripts
The Spread of Foxy
Second Parasite-- Transposons
First Schism
Improved Gene Regulation
Cell Structures
Eukaryote Explosion
Multi-Cellular Scripts
Cambrian Explosion
Appendix 1-- Prebiotic Earth
Appendix 2-- Primordial Puddles
Appendix 3-- Primordial Catalysts
Appendix 4-- C Value Enigma
Cast of Characters

Now let's poke at some of the details on this Fred thing.

Reading Frame

First of all, if you know anything about modern genetics, you may be thinking, “Wait a minute, it takes three nucleic acids to specify an amino acid!” And it's true that in modern living organisms, that's exactly how protein transcription works. There are clever packages of proteins and RNA chains in the ribosomes that 'read' three RNA nucleotides at a time, and then pick one of twenty different amino acids to add to a protein.

The problem is, that system requires many different proteins and helper molecules to work, and right now all we have is a world of random chemicals. None of those clever support proteins exist yet. If anything, it's quite lucky enough that Fred is able to do all that sensing and catalyzing within one small polypeptide, and even luckier that it happened to meet a Sofia.

There is still the basic 'chicken and egg' problem with protein replication, and right now we have neither chickens nor eggs. Fred needs to be absolutely as simple as possible, to have a reasonable chance of actually appearing in some puddle. Such a short chain would never be able to bend into a shape that could choose among 20 different amino acids. Nor could it jiggle reliably across three chain molecules at a time.

Fred's simple two-way switch mechanism is far less efficient than the three-base-pair coding system used by modern DNA, and it's not nearly as specific about the amino acids that it adds to a polypeptide. But it does manage to work without help from any other enzymes.

In other words, Fred uses a simple 'reading frame' of just one chain molecule, because triplet reading frames are just too darned complicated for this very earliest stage of life.

Gene Composition

If you know much about DNA, you are probably also wondering why we have been so vague about Sofia. Shouldn't it be built with the base pairs found in DNA or RNA? After all, DNA is the main topic of this book.

Well, Sofia might include adenine, cytosine, guanine, thymine or uracil-- either in their full nucleotide form (linked with a ribose sugar and a phosphate bond), or bonded together with some other sort of bridge molecule between them, or perhaps just sitting loosely in a chain with nothing but hydrophobia to keep them together.

However, right now we still in a world of completely random chemicals, and it's just as likely that the Sofia polymer was made of something entirely different. Just two random whatever molecules that happened to be found in quantity in the local puddle.

To make a functional Sofia, it is sufficient to have any two compounds which line up into a fairly rigid chain, when polymerized. There only needs to be enough difference between them, that Fred changes conformation when it is next to each molecule in the chain.

For chemical reasons, the odds are good that the chain compounds had aromatic rings (since aromatic compounds are flat, and 'stack' easily into a relatively rigid chain or helix). But, otherwise, there are no specific chemical or physical requirements for Sofia's two components.

A purine and a pyrimidine would do the trick, or two purines with different attachments. Or two pyrimidines with different attachments. Or some other aromatic compounds with polar attachments on their edges . Or possibly some entirely different types of compounds, with very different chemical properties.

Transcription Accuracy

You may also notice that Fred is rather a dim bulb when it comes to detailing proteins. Conformational changes being what they are, Fred's elbow can only read two different chain molecules, and distinguishing between two types of amino acids is about the best that Fred's knee can do.

That's not a problem in this particular puddle, where there are high concentrations of two specific amino acids, and two different chain molecules. However, realistically, even in the 'home puddle' we can expect there to be a few other random amino acids floating about. Sometimes they will substitute for one of the amino acids in the output chain, and Fred will not make a faithful transcription.

In fact, a high percentage of Fred and Sofia's first creations will not be exact copies of Fred. Sometimes Fred will start in the middle of Sofia, and produce half a Fred. Sometimes a wrong jolt of energy will shove its knee, and let the wrong amino acid slip in. Sometimes Fred won't jiggle properly, and it will add an extra amino acid, or skip one.

Perfect, functional Freds are not going to just roll off the assembly line from our very first Fred and our very first Sofia, even under the best of conditions. After all, this is the very first self-replication, and we really can't expect it to proceed with the efficiency of modern life.


Another issue for Fred is energy. In a dilute water solution, amino acids prefer to split up into individual molecules, rather than join together, and Fred has no source of energy to force them together.

About the only place that Fred can work is in a concentrated, salty solution, where the hydrodynamic forces are reversed, and amino acids will spontaneously clump into proteinoid compounds, even without any catalytic help.

In that environment, about all Fred needs to do is to attract the right type of amino acid to the end of a growing chain, and/or repulse the wrong type. At that point, the concentrated, salty environment will suck a water molecule out of the two molecules, and they will merge.

So, for the moment, Fred can only work in puddles that are above high tide, but within the reach of occasional wave splash. Those 'condensing' puddles provide the high density of raw materials and the concentrated, salty solutions that allow Fred to work.

Local Concentrations

In fact, having a highly concentrated solution of raw materials is not all that Fred needs. Its replication system is extremely dependent on the exact conditions in its neighborhood, since there needs to be a high concentration of just two specific amino acids, and hardly any similar molecules.

The problem is that Fred is just not very clever at distinguishing between different amino acids. When it is ready to add a new polar amino acid to its new chain, any polar amino acid will do. And the same thing happens when it adds a new hydrophobic molecule. In a place with a mixture of amino acids, Fred would still build a new polypeptide with the correct sequence of polars and hydrophobics. Unfortunately, the molecules would be different enough from the originals that the end product would not work like a Fred.

You might say that other amino acids are poisons to Fred, since they interfere with its transcription process. Pretty much any other amino acid would be lethal, so Fred can only work in those very rare puddles that have high concentrations of exactly two just-right amino acids.

Because of that dependency, Fred is completely useless in the open ocean. Its simple-minded approach to replication means it has only a tiny chance of replicating itself from a large mix of possible amino acids. For a 20-acid chain in a sea of 20 different amino acids, the odds of self-replication would be one in 2020, or about 1 in a hundred septillion, which is not lucky at all . In fact, the primordial ocean was even more hostile than that, with many alternate amino acids and unrelated compounds that Fred might have liked just as much as the correct amino acid.

In short, Fred can't survive around clutter, but it can just scrape by in the exceptionally friendly world of an isolated and very opportune puddle, which contains concentrations of exactly two amino acids. In the right location, Fred is capable of turning the mind-numbingly unlikely chance of self-replication into a moderately plausible one.

Multiply that small chance by a few quadrillion shoreline micro-puddles and a few million years, and the odds that a Fred and a Sofia will meet each other drifts into the realm of the possible.

Information Content

One way to look at Fred's situation is to consider the quantity of choices it had to make. The two-molecule puddle had a reduced information content, which makes it easier for Fred to make 'good' choices when it comes to building proteins.

Living in an isolated micro-puddle may have been boring for our first molecules, but they just weren't sophisticated enough to stand the 'way too much information' world of the primordial seas.

In fact, living the simple life will be a recurring theme, as life develops. Even the most modern of cells will die if exposed to a mish-mash of random chemicals, so they still have the same need to simply and control their chemical environment.

About the only difference between real life and Fred is that cells have membranes and other cell structures that help create an ideal environment next to each enzyme. We'll talk about that more, as we get further along in this story.

Who's Your Daddy?

If you think about Fred for a while, you may notice that the very first starter Fred could have been very different from the first Fred progeny that was replicated from Sofia.

First Fred may have been made of different amino acids, or it may have been composed of entirely different organic compounds that weren't even amino acids. As long as Sofia had the right sequence, the first Fred would have created a self-replicating protein from Sofia, even though that new Fred was different from its transcriber.

Of course, once there was a second copy of Fred, the child Freds would also read Sofia and create more child Freds. Gradually, they would become dominant, and the very first accidental grampa Fred would eventually fade from the evolutionary scene, unremembered and unloved, puttering around in pajamas in some molecular nursing home, somewhere, trying to remember the name of that cute little chain it hung out with way back when.

It may be possible to do some biochemical detective work and track down the sequence for the first child Freds, but we'll never ever know for sure about the mysterious enzymatic stranger that entered Sofia's life so briefly, and caused so much excitement.

Chicken and Egg

Another interesting fact to consider is that right from the very beginning, we have a protein enzyme and a genetic chain happening both at the same time .

That means that the answer to the chicken-and-egg question for DNA and proteins is 'both'.

Right from the beginning, we have proteins doing what they do best-- acting catalytically and structurally. And a genetic chain molecule is doing what it does best-- carrying information and deciding how to build proteins.

As we'll see in later chapters, these two types of organic compounds will stick around, and gradually develop into more and more life-like forms. There are plenty of complications that we'll get to later, but at least there is no need for an awkward shift of function for any of our starter molecules, as they make the gradual transition into life.