However, we—you and I and the potted begonia in the corner—are not composed entirely of DNA. We have seen how the DNA molecule takes care of itself, but what makes the rest of us?
That calls for some agent to interpret and use the code contained in the DNA molecule. It is a two-stage process. First, another nucleic acid, RNA (ribonucleic acid), copies the information in the DNA molecule onto itself. It has a slightly different chemical composition (uracil, abbreviated to U, takes the place of thymine), but essentially it mimics the relevant DNA structure with matching bases. Note that, because RNA can match any sequence of sites in a DNA molecule, RNA can carry the same information as DNA.
What RNA cannot do, because it lacks the double helix structure, is make a copy of itself. We will return to that later.
RNA copies information from the DNA molecule. Then it goes off to a place in the living cell where small round objects known as ribosomes are located. There, the RNA dictates the production of substances known as amino acids. The amino acids are the small and simple elements from which large and complex protein molecules are made. Just as DNA and RNA have strings of nucleotide bases, proteins have strings of amino acids. Each triplet of symbols in the RNA bases (A, C, G, and U) leads to the production of a unique amino acid. For example, the sequence U-A-C always, without exception, leads to the production of the amino acid tyrosine. The order of the sequence is important; C-A-U leads not to tyrosine, but to another amino acid, histidine.
Although each triplet leads to a unique amino acid, the converse is not true. There are 64 possible three-letter combinations, but they lead to only 20 amino acids. For example, both C-A-U and C-A-C produce histidine.
Now we have the final step: amino acids, created in the order dictated by the triplets (known as codons) in the RNA, in turn produce the proteins.
Interestingly, not all the three billion nucleotide bases in human DNA are used to make proteins. Only about ten percent of them do that. The other ninety percent, stretches of DNA that are known as "introns," don't seem to do anything at all. That may reflect current ignorance, and we will later learn what this "junk DNA" actually does. Simple organisms don't have introns—all their DNA is used to define the making of proteins. So why do more complex organisms have them?
Feel free to make up your own reasons. No one is in a position to disagree with you.
We have rendered down a century of work to a few hundred words, but the central message, stated by Francis Crick as the "Central Dogma of molecular biology," is simple: DNA codes for the production of proteins; the process never, ever, goes the other way.
There is another way of looking at this, and one that may sound more familiar. DNA controls reproduction, and also the production of proteins and hence our bodies. Nothing that we do to our bodies can ever go back and affect the DNA. In other words, there can be no inheritance of acquired characteristics.
6.2 The mystery of sex. Before we move on to other mysteries of biology, we need to answer an implied question. We can be regarded, as Richard Dawkins has eloquently pointed out in The Selfish Gene (Dawkins, 1976), as nothing more than large-scale mechanisms designed to propagate our own genetic material. To most organisms, DNA is the most precious thing in the world, the only way to assure that their line continues. Few people would argue, seeing the powerful imperative to propagate as we see it displayed throughout the living world, that the preservation and multiplication of genetic material is the Prime Directive of nature.
However, when we examine the subject of sex logically (a mental exercise for which, as any newspaper will show, humans show little apparent aptitude) we find a paradox. Your DNA is high-quality stuff, developed and fine-tuned over four billion years. It is you, the essence of you, the only way for you to continue an existence in the future (let us leave aside for the moment the notion of your and my possibly immortal prose).
So what do you do? You mate, with a genetic stranger. At that point your unique and wonderful DNA becomes mixed, fifty-fifty, with other DNA about which you know very little. Even if you have known your partner all your life, it is still true to say that the two of you are strangers at the DNA level. Indeed, the best bet from the point of view of your genes would be to mate with a close relative, where you share a high proportion of common genetic material.
This is not, of course, what happens. Incest is taboo in most human societies and mating outside the family seems generally preferred everywhere.
What is going on? Why, taking a gene's-eye view of things, is sexual reproduction such a big hit? Why do all the most complex life forms on Earth employ, all or part of the time, sex as a tool for propagation?
I do not think that biology today offers complete answers to these question. Richard Dawkins at one point seems all ready to tackle it in Climbing Mount Improbable (Dawkins, 1996). But then he veers away, or at least postpones: "But the whole question of sex and why it is there . . . is another story and a difficult one to tell. Maybe one day I'll summon up the courage to tackle it in full and write a whole book about the evolution of sex."
I wish he would. Meanwhile, here is a brief analysis, some of it based on personal speculation. In summary, the main idea is that the driving force for rapid change, and hence for exploiting a changing environment, is selection, not mutation.
Let me repeat and rephrase an earlier statement which I believe is not controversial: changes that take place in an organism over time, as a result of random mutation, take place slowly. Each mutation may be harmful, beneficial, or neutral in terms of survival of the organism's offspring. Beneficial mutations will prosper (there is something of a tautology here, since the definition of beneficial is that organisms with the mutation do well). However, significant changes as a result of mutation require many thousands of generations.
Also changing over time is the environment in which the organism lives. The environmental changes may be slow (tectonic forces that raise mountain ranges) or fast (earthquake and volcano), but in any case their rates of change are largely independent of the rates of organism mutation. I say largely, because changes in chemistry or radioactivity levels certainly affect mutation rates.
Consider changes in environment which take place over time scales that are, in terms of mutation rates, very fast. A volcanic eruption, like Mount Pinatubo in 1993, fills the upper atmosphere with dust and cools the atmosphere by a few degrees. El Niño, in 1998, causes anomalous heating of the seas. A large calving of the Antarctic ice shelf reduces salinity over much of the southern oceans.
An organism which reproduces asexually will adapt to such changes to the limits of its variability. We can use the term "natural selection" to describe this process, but it will not normally be mutation. An organism cannot mutate fast enough to be useful, nor can it modify its own genetic material. It passes on to the next generation an identical copy of what it possesses.
Now consider sexual reproduction. The mixing of genetic material permits a great variety in offspring, in both appearance and function. Thus adaptation of organisms, accompanied by rapid morphological changes, can be far faster than mutation would permit. Consider the "unnatural selection" process that has led to forms of a single species as disparate in size and shape as the Chihuahua and the Great Dane, during the relatively short period of human domestication of animals. Morphological evolution can be fast, when something (humans or Nature) drives it. It will be slow when there is no driving force for change. However, in either case the available pool of DNA for the whole sexually-compatible group of organisms is unchanged, though grossly variable at the individual level. Thus a species can adapt and thrive, using sexual reproduction, without waiting for the slow process of favorable mutation. This is a huge evolutionary advantage.
We still have to address an important question: Is it possible for changes to take place in an organism, sufficient that we can say we now have a new species, other than by the slow processes of mutation? If not, then although in the short run sexual reproduction has an advantage
over asexual reproduction, in the long term that advantage diminishes.
I argue that there is also the following long-term gain in sexual reproduction. When a male and female produce offspring, they mix their DNA fifty-fifty. However, this is not a random mixing. Certain very specific segments of DNA, which we call genes, come from one parent, and this is an all-or-nothing process. Thus, an offspring gets that whole segment from one parent, or from the other. It does not get half and half, or if it does get a fractional gene, the result cannot survive. Since there are thousands of segments (genes) we have a gigantic number of possible offspring, with all sorts of gene mixes.
Now take one group of offspring away to a different environment. Natural selection takes place, and some gene segments, rather than existing in the population equally in their two possible forms, are preferred because of environmental pressures in just one form. Offspring with that form thrive, others fail. The organisms begin to look and act differently from the original form, because their gene choices are selected to suit the new environment. Finally, one form of a gene may exist in the new environment, while the complementary form of the gene, selected against, does not. It has been removed completely from the organisms in that environment.
In the same way, in some other environment, other genes have a preferred form for organism survival. Their complementary form does not exist in that environment.
If mutations did not occur and we put specimens of organisms from the two environments back into their original settings, they would mate and their offspring would have all the original forms of genes.
However, we cannot ignore mutation completely. It is a random process, but it happens. A beneficial mutation will spread rapidly through a population. We might say that we had a new species every time such a mutation occurred and spread, except that we will normally have no way of observing such a change. Over time, however, there will be recognizable changes, and we then say that the organism has evolved. We would see the evolution of a single species, whether or not the organism propagates sexually.
Now here is the key, if obvious, piece of the argument: mutations cannot occur in genes that are not present in an organism. Different environments, for sexually reproducing organisms, will have different mutations. At some point, the original organisms that were placed into two different environments will be different not only morphologically in appearance and behavior (accomplished via sexual selection of genes), but through the accumulation of different changes in their actual genetic make-up. The new versions of genes will not be compatible with the old complementary set of genes. We see speciation. One species has become two. And that process, the creation of new permanent forms, is easier and faster with the aid of sexual reproduction. Sex is, in fact, a good thing.
At this point, I ought to say that not everyone agrees as to why sex is a good thing. Steven Pinker, in How the Mind Works (1997) supports a different theory as to why sex was a valuable invention for living creatures. First, he points out that an organism cannot practice any policy that implies present sacrifice for future benefit. "Playing on the come" will not work, since everything from squash to squids must maximize the number of its immediate descendants. (Not only that, an organism does not sacrifice itself, even for the good of the species, unless there are sound reasons, based on the selfishness of genes, for doing so. This has caused workers, including Dawkins, considerable trouble, explaining how altruism can also be a form of self-interest.)
Pinker favors a theory proposed by John Tooby, which claims that sex was developed as a way of protecting organisms against disease. The argument goes as follows: We are invaded all the time by a variety of tiny critters, who see us as a plentiful food supply. We have built up protections against them, but they in turn have become very cunning at penetrating our defenses. When an organism employs asexual reproduction, and some parasite organism finds a way around the defense, the game is over, because the same trick will penetrate the defenses of future generations with identical genetic make-up. Sexual reproduction, however, scrambles the genes, and makes the offspring less susceptible to parasitic invasion. Thus, sex provides a partial fresh start with each generation.
I am less persuaded than Pinker by this argument (although I strongly recommend How the Mind Works for a hundred other good reasons). It seems to me that there is no inconsistency between optimizing for the present generation, and sexual reproduction. In fact, the mixing of genes that sex offers increases the total variation in the next generation, without the dangers presented by mutation (which is normally unfavorable to an organism), and therefore improves the short-term odds.
Which theory is right? I don't know. Nor, I argue, does anyone else. However, this is not an either/or situation, where one theory must be right at the expense of another. Perhaps sexual reproduction allows organisms to adapt more rapidly to new environmental niches, and also serves as a defense against disease.
Is there a third reason why sexual reproduction has been such an overwhelming success? Feel free to conjecture. Alternate scientific theories are exactly the place where science fiction stories flourish. And if you would like to read a radically different suggestion as to why evolution seems to proceed far more rapidly than simple mutation would suggest, try Paths to Otherwhere (Hogan, 1996), where the subject is dealt with, amazingly, in terms of the many-worlds theory of Everett and Wheeler (see Chapter 2).
6.3 Viruses, RNA, prions, and the origin of life. The story of DNA seems astonishingly simple and complete. Let us ask the usual questions: What don't we know, and what do we know what ain't so?
For one thing, we don't know how this whole process started.
The interdependence of the proteins and the DNA is a highly improbable connection. To make a new cell, both are needed. If you lack either one, the process cannot work. It seems ridiculous to suggest that both DNA and the necessary protein production factory could have developed independently of each other, and work together without a hitch. It is as though you developed a car body while I, without consulting you, developed an engine, neither of us having done anything like it before. We put them together, and the whole automobile runs like a dream.
It would be a dream. That independent development of DNA and proteins is obviously not what happened. But what did?
To provide a possible explanation, we go to the world of viruses. At first that may seem to make the problem worse. A virus is a mystery organism (but a godsend, I sometimes feel, for the medical profession. The doctor's pronouncement, "You have a virus," is often the equivalent of, "I don't know what is wrong with you, but I know I can't give you anything to cure it.").
Viruses are minute, much smaller even than cells. Their small size is possible because they lack a cell structure or a protective cell wall, and they don't have their own ribosome protein factories. All they are is a tiny chunk of DNA, wrapped in a coat of protein. Some of them also have little tails.
It is possible that viruses are degenerate forms, organisms that once possessed the full machinery for self-reproduction but at some point abandoned it. Be that as it may, we must still explain how something so small, on the very borderline between living and nonliving, can go about reproducing itself when it has none of the equipment we have described as necessary. If we find the answer to that, maybe we will solve the problem of the separate development of proteins and DNA.
A memorable report in a British newspaper of a divorce court proceeding a few years ago ended as follows (with minor changes as to names): "Living at the time as a paying house-guest of Mr. and Mrs. Smith was Mr. Jones, a man with an artificial leg. One day Mrs. Smith asked her husband, if a woman had a baby by Mr. Jones, would the baby have an artificial leg? Mr. Smith then began to be suspicious."
If, metaphorically speaking, the paying guest in your house happened to be a virus, then the chance of your cells having an artificial leg would be very good indeed.
What happens is this. The virus penetrates the wall of a normal, healthy cell, often with the ai
d of its little tail of protein. Once inside, the virus takes over the cell's own copying equipment, using it to produce hundreds or thousands of new viruses until the chemical supplies of the cell are used up. Then the cell wall bursts, releasing the viruses, which go on to repeat the process. The virus doesn't carry its own protein factory, because it doesn't need it. Viruses are, and must be, parasitic on cells.
Again, the story seems neat and complete, but not useful to resolve our mystery of how the whole process began. Then, to add confusion, certain viruses were discovered that have no DNA at all.
What they have is RNA. Such viruses are known as retroviruses, and they are famous, or infamous, because their number includes the Human Immunodeficiency Virus, HIV, associated with the disease AIDS. (The naming of the HIV virus, and the battle over priority of discovery, is an astonishing story that I won't go into here. Science is the search for absolute truth, and scientists are objective, dispassionate people. Right? Look out of the window, and you will see the Easter Bunny.)
How can something without DNA reproduce? We have emphasized the importance of the DNA double spiral, which RNA lacks. A retrovirus has to work hard indeed to produce the next generation. First, it invades a cell. Next, it uses the one-to-one correspondence between its own RNA bases (A, C, G, U) to make matching DNA (T, G, C, A). Then it employs the cell's own DNA-reproducing mechanism to make DNA copies. Finally, the virus employs the rest of the cell machinery to make matching RNA (its own genetic material) and hence more copies of itself.
Borderlands of Science Page 14
