Gödel, Escher, Bach: An Eternal Golden Braid (94 page)

The real name for such a clover is
transfer
RNA
. A molecule of t
RNA
is quite small-about the size of a very small protein-and consists of a chain of about eighty nucleotides. Like m
RNA
, t
RNA
molecules are made by
transcription
off of the grand cellular template, DNA.

However, tRNA's are tiny by comparison with the huge mRNA molecules, which may contain thousands of nucleotides in long, long chains. Also, t
RNA
's resemble proteins (and are unlike strands of m
RNA
) in this respect: they have fixed, well-defined tertiary structures-determined by their primary structure. A t
RNA
molecule's tertiary structure allows precisely one amino acid to bind to its amino-acid site: to be sure, it is that one dictated according to the Genetic Code by the anticodon on the opposite arm. A vivid image of the function of tRNA molecules is as flashcards floating in a cloud around a simultaneous interpreter, who snaps one out of the air-invariably the right one!-whenever he needs to translate a word. In this case, the interpreter is the ribosome, the words are codons, and their translations are amino acids.

In order for the inner message of
DNA
to get decoded by the ribosomes, the t
RNA
flashcards must be floating about in the cytoplasm. In some sense, the t
RNA
s contain the essence of the outer message of the
DNA
, since they are the keys to the process of translation. But they themselves came from the
DNA
. Thus, the outer message is trying to be part of the inner message, in a way reminiscent of the message-in-a-bottle which tells what language it is written in. Naturally, no such attempt can be totally successful: there is no way for the
DNA
to hoist itself by its own bootstraps. Some amount of knowledge of the Genetic Code must already be present in the cell beforehand, to allow the manufacture of those enzymes which transcribe tRNA's themselves off of the master copy of
DNA
. And this knowledge resides in previously manufactured t
RNA
molecules. This attempt to obviate the need for any outer message at all is like the Escher dragon, who tries as hard as he can, within the context of the two-dimensional world to which he is constrained, to be threedimensional. He seems to go a long way-but of course he never makes it, despite the fine imitation he gives of three-dimensionality.

Punctuation and the Reading Frame

How does a ribosome know when a protein is done? Just as in Typogenetics, there is a signal inside the m
RNA
which indicates the termination or initiation of a protein. In fact, three special codons-
UAA, CAG, UGA
act as
punctuation
marks instead of coding for amino acids. Whenever such a triplet clicks its way into the "reading head" of a ribosome, the ribosome releases the protein under construction and begins a new one.

Recently, the entire genome of the tiniest known virus, φ)X174, has been laid bare.

One most unexpected discovery was made en route: some of its nine genes overlap-that is,
two distinct proteins are coded for by the same stretch of
DNA
! There is even one gene contained entirely inside another!

This is accomplished by having the reading frames of the two genes shifted relative to each other, by exactly one unit. The density of information packing in such a scheme is incredible.

This is, of course, the inspiration behind the strange "5/17 haiku" in Achilles' fortune cookie, in the
Canon byIntervallic Augmentation
,

Recap

In brief, then, this picture emerges: from its central throne, DNA sends off long strands of messenger RNA to the ribosomes in the cytoplasm; and the ribosomes, making use of the

"flashcards" of tRNA hovering about them, efficiently construct proteins, amino acid by amino acid, according to the blueprint contained in the mRNA. Only the primary structure of the proteins is dictated by the DNA; but this is enough, for as they emerge from the ribosomes, the proteins "magically" fold up into complex conformations which then have the ability to act as powerful chemical machines.

Levels of Structure and Meaning in Proteins and Music

We have been using this image of ribosome as tape recorder, mRNA as tape, and protein as music. It may seem arbitrary, and yet there are some beautiful parallels. Music is not a mere linear sequence of notes. Our minds perceive pieces of music on a level far higher than that.

We chunk notes into phrases, phrases into melodies, melodies into movements, and movements into full pieces. Similarly, proteins only make sense when they act as chunked units. Although a primary structure carries all the information for the tertiary structure to be created, it still "feels" like less, for its potential is only realized when the tertiary structure is actually physically created.

Incidentally, we have been referring only to primary and tertiary structures, and you may well wonder whatever happened to the secondary structure. Indeed, it exists, as does a quaternary structure, as well. The folding-up of a protein occurs at more than one level.

Specifically, at some points along the chain of amino acids, there may be a tendency to form a kind of helix, called the alpha helix (not to be confused with the DNA double helix). This helical twisting of a protein is on a lower level than its tertiary structure. This level of structure is visible in Figure 95. Quaternary structure can be directly compared with the building of 'a musical piece out of independent movements, for it involves the assembly of'

several distinct polypeptides, already in their full-blown tertiary beauty, into a larger structure. The binding of these independent chains is usually accomplished by hydrogen bonds, rather than covalent bonds; this is of course just as with pieces of music composed of several movements, which are far less tightly bound to each other than they are internally, but which nevertheless form a tight "organic" whole.

The four levels of primary, secondary, tertiary, and quaternary structure can also be compared to the four levels of the MU-picture (Fig. 60) in

the
Prelude, Ant Fugue
. The global structure-consisting of the letters 'M' and 'U'-is its quaternary structure; then each of those two parts has a tertiary structure, consisting of

"HOLISM" or "REDUCTIONISM"; and then the opposite word exists on the secondary level, and at bottom, the primary structure is once again the word "MU", over and over again.

Polyribosomes and Two-Tiered Canons

Now we come to another lovely parallel between tape recorders translating tape into music and ribosomes translating mRNA into proteins. Imagine a collection of many tape recorders, arranged in a row, evenly spaced. We might call this array a "polyrecorder". Now imagine a single tape passing serially through the playing heads of all the component recorders. If the tape contains a single long melody, then the output will be a many-voiced canon, of course, with the delay determined by the time it takes the tape to get from one tape recorder to the next. In cells, such "molecular canons" do indeed exist, where many ribosomes, spaced out in long lines-forming what is called a polyribosome-all "play" the same strand of mRNA, producing identical proteins, staggered in time (see Fig. 97).

Not only this, but nature goes one better. Recall that mRNA is made by transcription off of DNA; the enzymes which are responsible for this process are called RNA polymerases ("-ase" is a general suffix for enzymes). It happens often that a series of RNA polymerases will be at work in parallel on a single strand of DNA, with the result that many separate (but identical) strands of mRNA are being produced, each delayed with respect to the other by the time required for the DNA to slide from one RNA polymerase to the next. At the same time, there can be several different ribosomes working on each of the parallel emerging mRNA's.

Thus one arrives at a double-decker, or two-tiered, "molecular canon" (Fig. 98). The corresponding image in music is a rather fanciful but amusing scenario: several FIGURE 98. Here, an even more complex scheme. Not just one but several strands of mRNA, all emerging by transcription from a single strand of DNA, are acted upon by polyribosomes. The result is a two-tiered molecular canon. [From Hanawalt and Haynes, The Chemical Basis of Life, p. 271]

different copyists are all at work simultaneously, each one of them copying the same original manuscript from a clef which flutists cannot read into a clef which they can read. As each copyist finishes a page of the original manuscript, he passes it on to the next copyist, and starts transcribing a new page himself. Meanwhile, from each score emerging from the pens of the copyists, a set of flutists are reading and tooting the melody, each flutist delayed with respect to the others who are reading from the same sheet. This rather wild image gives, perhaps, an idea of some of the complexity of the processes which are going on in each and every cell of your body during every second of every day ...

Which Came First-The Ribosome or the Protein?

We have been talking about these wonderful beasts called ribosomes; but what are they themselves composed of? How are they made? Ribosomes are composed of two types of things: (1) various kinds of proteins, and (2) another kind of RNA, called ribosomal RNA (rRNA). Thus, in order for a ribosome to be made, certain kinds of proteins must be present, and rRNA must be present. Of course, for proteins to be present, ribosomes must be there to make them. So how do you get around the vicious circle? Which comes first-the ribosome or the protein? Which makes which? Of course there is no answer because one always traces things back to previous members of the same class just as with the chicken-and-the-egg question-until everything vanishes over the horizon of time. In any case, ribosomes are made of two pieces, a large and a small one, each of which contains some rRNA and some proteins.

Ribosomes are about the size of large proteins; they are much much smaller than the strands of mRNA which they take as input, and along which they move.

Protein Function

We have spoken somewhat of the structure of proteins-specifically enzymes; but we have not really mentioned the kinds of tasks which they perform in the cell, nor how they do them. All enzymes are catalysts, which means that in a certain sense, they do no more than selectively accelerate various chemical processes in the cell, rather than make things happen which without them never could happen. An enzyme realizes certain pathways out of the myriad myriad potentialities. Therefore, in choosing which enzymes shall be present, you choose what shall happen and what shall not happen-despite the fact that, theoretically speaking, there is a nonzero probability for any cellular process to happen spontaneously, without the aid of catalysts.

Now how do enzymes act upon the molecules of the cell? As has been mentioned, enzymes are folded-up polypeptide chains. In every enzyme, there is a cleft or pocket or some other clearly-defined surface feature where the enzyme hinds to some other kind of molecule. This location is

called its active site, and any molecule which gets bound there is called a substrate. Enzymes may have more than one active site, and more than one substrate. Just as in Typogenetics, enzymes are indeed very choosy about what they will operate upon. The active site usually is quite specific, and allows just one kind of molecule to bind to it, although there are sometimes "decoys"-other molecules which can fit in the active site and clog it up, fooling the enzyme and in fact rendering it inactive.