Mystery at the Heart of Life

The secret life of cells /

Our bodies are made up of some 100 trillion cells. We tend to think of cells as static, because that’s how they were presented to us in textbooks. In fact, the cell is like the most antic, madcap, crowded (yet fantastically efficient) city you can picture. And at its heart lies a mystery—or I should say, several mysteries—involving three special kinds of molecules: DNA, RNA, and proteins.

These molecules are assembled into long chains called polymers, and are uniquely suited for the roles they play. More importantly, life absolutely depends upon them. We have to have DNA, RNA, and protein all present and active at the same time for a living organism to live.

How they work together so optimally and efficiently is not merely amazing, but also a great enigma, a mystery that lies at the heart of life itself.

Madcap Copying and Keystone Cops

First, a word about these special molecules and how they are produced.

We begin with the nucleus at the center of a cell. The nucleus is something like the cell’s Library of Congress, where instructions are stored for making most everything the cell needs.

The medium on which the information is stored is DNA, two long chains linked together and wound around each other—like two strands of wires wrapped about each other (except that the “wire” is made up of small units called nucleotides linked together). The nucleotides come in four different shapes that we have named with four letters: A, C, T, and G. These chains are linked together in a very specific way.

Imagine DNA as a long jigsaw puzzle exactly two pieces wide, with only four kinds of jigsaw pieces (or nucleotides): A, C, T, and G. Along each row, or strand, the pieces can be arranged in any order—they all lock together in exactly the same way along the row, so any piece can be joined to any other. But between the rows, there is only one way to pair them up. C only fits G, and T only fits A. The result, if printed out, would look something like this:



Notice that any nucleotide can be next to any other along the length of the row, or strand of DNA, but between the strands, A always pairs with T, and G always pairs with C. The information in DNA comes from the sequence along each strand, just like the information in printed text comes from the sequence of letters in a sentence. But there is no information in the pattern of bonding between strands, just a simple rule about which nucleotide pairs with which. These rules carry no information, but they do make it easy to copy DNA, as you will see.

The DNA in your cells is very long, much longer than the little bit typed above. When I say much longer, I mean much longer. If all the DNA in just one of your cells were written out just as it is above, it would stretch from Minnesota to Hawaii—nearly 4,000 miles.

Tightly coiled DNA, in turn, makes up chromosomes. If your DNA is like a giant print library, then chromosomes are like vast sections of that library. You have two sets of chromosomes, making a total of 46 altogether. In each chromosome, large portions of the DNA are not only tightly coiled but also packed against the nuclear wall, inactive—like books that have been stored in deep archives. Which books are stored depends on what cell type it is.

Nearer the center of the nucleus, active sections of each chromosome are found in certain regions, just like books are organized in the stacks of the Library of Congress. In the very center, unwound loops of DNA (the books that are actually being read) cluster together. Swarming about the DNA strands are proteins that interact with each other and with the DNA.

(OK, hold it. What’s a protein? Proteins are special strings of molecules that perform a number of critical tasks. Among other things, they move things, they digest things, and they build long chains of DNA and RNA.)

Those proteins swarming around the DNA determine which genes will be turned on and which will be turned off. (A gene is a stretch of DNA that has the information for how to make one or more proteins.) If the right combinations of proteins attach to the DNA in the right locations, the neighboring genes will be activated for transcription.

Being activated for transcription means this: A very particular binding protein made just for this role (which had been drifting around, waiting for the signal to bind) sits down on the DNA like a rider in a saddle, in a particular place right in front of a gene. This protein begins to attract other proteins to itself, one by one. When this cluster of proteins gets large enough—all connected to the DNA—the cluster attracts another wandering specialized protein called an RNA polymerase. (Ah—a polymerase is a protein that makes polymers of RNA!)

Everything is nearly ready now. The whole complex of proteins waits like a racehorse in the starting gate until the signal is given, then bang! The polymerase takes off, leaving the other proteins behind, and starts copying DNA into RNA at an astonishing clip of 30 nucleotides per second. A professional typist can type on the order of 330 characters per minute, or about 5.5 characters per second. The polymerase is 6 times faster.

Sometimes the polymerase jumps between strands of DNA, forming an RNA strand copied from two separate chromosomes. Sometimes polymerases racing in opposite directions run into each other, like Keystone cops. And sometimes polymerases run into places where DNA is being duplicated in order for the cell to divide. The RNA polymerase politely steps aside.

As it travels, this enzyme and its helper proteins literally unzip the double-stranded DNA and make a copy of one of the strands.

What do I mean by making a copy? To copy the information is very simple. You just need to know the rule. Unwind the strand, and pair complementary nucleotides: C pairs with G, and T pairs with A. Just one tiny little difference from copying DNA. The RNA polymerase inserts a ribonucleotide called U in the place of T, so where there is an A it inserts a U on the growing strand.


U G A C C G A A U U A C ? ? ? ? ? ? ? ? ? ? ? ? ? ? ?

Go ahead. Finish the pattern as the polymerase would. This is the magic of the structure of DNA. Unzip and follow a simple rule for copying, and you can generate whole new copies of DNA or RNA as needed.

What happens to the RNA once it has been copied? It gets processed and shipped out to the cytoplasm (the cytoplasm includes everything else in the cell but the nucleus, and it’s where most of the action of the cell takes place). There, the RNA is turned into protein, such as the polymerase and binding proteins I have already mentioned, or the thousands of other proteins the cell requires.

Which Came First?

Here’s a conundrum: You may have noticed that these proteins are all generated by the DNA—as we have seen, DNA is copied into RNA, then RNA is translated into protein.

Consequently, proteins cannot exist without DNA.

However, DNA cannot exist without proteins either.

For example, to replicate DNA, one protein unwinds the DNA, creating a fork with two strands; another protein duplicates the right strand of the DNA, while yet another casts off loops from the left strand so it can be copied. Meanwhile, thirty or so other proteins keep watch over the DNA, proofreading, correcting, and ensuring very few errors—about one mistake per billion nucleotides copied.

In short, it’s a chicken and egg problem: which came first, proteins or DNA?

Even if that problem could be solved, another puzzle would remain: how the link between DNA, RNA, and protein came about. We know how it’s done—ribosomes—but we have no idea how ribosomes came to be. Ribosomes are indispensable, efficient, self-correcting, decoding machines, and protein factories. They are made of many proteins woven together with RNA molecules into tangled knots that somehow work together to decode RNA. In fact, just deciphering into what shape those knots are tied won three scientists the 2009 Nobel Prize in Chemistry.

Born in the nucleus, ribosomes do their work in the cytoplasm. Messenger RNA (RNA copied from a protein-coding gene) finds a ribosome and begins feeding through like ticker tape. The ribosome reads the message and translates it into amino acids, stitching the amino acids together to make a protein.

Though not as fast as transcription, the ribosome manages a respectable rate of 6 to 9 amino acids per second, a little faster than the best of our typists. But consider this: there are 20-plus amino acids for the ribosome to sort through in order to find the right one for each unit to be translated. Given that kind of search process, 6 to 9 amino acids per second puts the ticker tape on fast forward.

One last thing—the ribosome is also self-correcting. As the protein advances, the ribosome double-checks its work, and if it notices a mistake, it backs up to correct the error, like I had to do as I typed this sentence.

Suffice it to say that the genetic code, and the fidelity of its replication, transcription, and translation, are obviously very important, considering all the error correction that goes on, and they are interdependent, highly optimized processes that are essential to life. At the very center of these processes is this mystery: which came first, the protein or the DNA? And how was the link between DNA and protein established? Some say RNA came first, but RNA is inherently unstable, easily degraded and limited in its chemical abilities. So the problem remains unsolved.

We may someday figure out some of these relationships, but as is the nature of things, more mysteries will be revealed as we do. In fact, it may well be that at the very center of life, of existence itself, there lie mysteries known only to God. In the meantime, though, God has given us both the ability and the desire to search out the truth about things. For as Proverbs 25:2 says, “It is the glory of God to conceal a matter; to search out a matter is the glory of kings.”

Ann Gauger is senior research scientist at the Biologic Institute.

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