Uncorrected mistakes in the message are propagated down to future generations. They “breed true.” These changes in the sequence of As, Cs, Gs, and Ts, including alterations of a single nucleotide, are called mutations. They introduce a fundamental and irreducible randomness into the history and nature of life. Some mutations may neither help nor hinder, occurring, for example, in long, repetitive sequences—containing redundant information—or in what we’ve called the handles of the molecular machine tools, or in untranscribed sequences between STOP and START. Many other mutations are deleterious. If you’re crafting superb machine tools and, while you’re not looking, someone introduces a few random changes into the computer instructions for manufacture, there isn’t much chance that the resulting machines, built according to the new, garbled instructions, will work better than the earlier model. Enough random changes in a complex set of instructions will cause serious harm.
But a few of the random changes, by luck, prove advantageous. For example, the sickle-cell trait we mentioned in the last chapter is caused by the mutation of a single nucleotide in the DNA, generating a difference of a single amino acid in the hemoglobin molecules that nucleotide helps code for; this in turn changes the shape of the red blood cell and interferes with its ability to carry oxygen, but at the same time it eventually kills the plasmodium parasites those cells contain. A lone mutation, one particular T turning into an A, is all it takes.
And, of course, not just the hemoglobin in red blood cells, but every part of the body, every aspect of life, is instructed by a particular DNA sequence. Every sequence is vulnerable to mutation. Some of these mutations cause changes more far-reaching than the sickle-cell trait, some less. Most are harmful, a few are helpful, and even the helpful ones may—like the sickle-cell mutation—represent a tradeoff, a compromise.
This is a principal means by which life evolves—exploiting imperfections in copying despite the cost. It is not how we would do it. It does not seem to be how a Deity intent on special creation would do it. The mutations have no plan, no direction behind them; their randomness seems chilling; progress, if any, is agonizingly slow. The process sacrifices all those beings who are now less fit to perform their life tasks because of the new mutation—crickets who no longer hop high, birds with malformed wings, dolphins gasping for breath, great elms succumbing to blight. Why not more efficient, more compassionate mutations? Why must resistance to malaria carry a penalty in anemia? We want to urge evolution to get to where it’s going and stop the endless cruelties. But life doesn’t know where it’s going. It has no long-term plan. There’s no end in mind. There’s no mind to keep an end in mind. The process is the opposite of teleology. Life is profligate, blind, at this level unconcerned with notions of justice. It can afford to waste multitudes.
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The evolutionary process could not have gone very far, though, if the mutation rate had been too high. In any given environment, there must be a delicate balance—simultaneously avoiding mutation rates so high that instructions for essential molecular machine tools are quickly garbled, and mutation rates so low that the organism is unable to retool when changes in the external environment require it to adapt or die.
There is a vast molecular industry that repairs or replaces damaged or mutated DNA. In a typical DNA molecule, hundreds of nucleotides are inspected every second and many nucleotide substitutions or errors corrected. The corrections are then themselves proofread, so that there is only about one error in every billion nucleotides copied. This is a standard of quality control and product reliability rarely reached in, say, publishing or automobile manufacture or microelectronics. (It is unheard of that a book this size, containing around a million letters would have no typographical errors; a 1% failure rate is common in automobile transmissions manufactured in America; advanced military weapons systems are typically down for repair some 10% of the time.) The proofreading and correction machinery devotes itself to DNA segments that are actively involved in controlling the chemistry of the cell, and mainly ignores nonfunctioning, largely untranscribed, or “nonsense” sequences.
The unrepaired mutations steadily accumulating in these normally silent regions of the DNA may lead (among other causes) to cancer and other illnesses, should the “STOP” be ignored, the sequence turned on, and the instructions carried out. Long-lived organisms such as humans devote considerable attention to repairing the silent regions; short-lived organisms such as mice do not, and often die filled with tumors.10 Longevity and DNA repair are connected.
Consider an early one-celled organism floating near the surface of the primeval sea—and thereby flooded with solar ultraviolet radiation. A small segment of its nucleotide sequence reads, let’s say, … TACTTCAGCTAG …
When ultraviolet light strikes DNA, it often binds two adjacent T nucleotides together by a second route, preventing DNA from exercising its coding function and getting in the way of its ability to reproduce itself: … TAC
The molecule literally gets tied up in knots. In many organisms enzymatic repair crews are called in to correct the damage. There are three or four different kinds of crews, each specialized for repairing a different kind of damage. They snip out the offending segment and its adjacent nucleotides (C
Advantageous mutations occur so rarely that sometimes—especially in a time of swift change—it may be helpful to arrange for an increased mutation rate. Mutator genes in such circumstances can themselves be selected for—that is, those varieties with active mutator genes serve up a wider menu of organisms for selection to draw upon, and serve them up faster. Mutator genes are nothing mysterious; some of them, for example, are just the genes ordinarily in charge of proofreading or repair. If they fail in their error-correcting role, the mutation rate, of course, goes up. Some mutator genes encode for the enzyme DNA polymerase, which we will meet again later; it’s in charge of duplicating DNA with high fidelity. If that gene goes bad, the mutation rate may rise quickly. Some mutator genes turn As into Gs; others, Cs into Ts, or vice versa. Some delete parts of the ACGT sequence. Others accomplish a frame shift, so the genetic code is read, three nucleotides at a time, as usual, but from a starting point offset by one nucleotide—-which can change the meaning of everything.11
This is a marvel of self-reflexive talent. Even very simple microorganisms have it. When conditions are stable, the precision of reproduction is stressed; when there’s an external crisis that needs attending to, an array of new genetic varieties is generated. It might look as if the microbes are conscious of their predicament, but they haven’t the foggiest notion of what’s going on. Those with appropriate genes preferentially survive. Active mutators in placid and stable times tend to die off. They are selected against. Reluctant mutators in quickly changing times are also selected against. Natural selection elicits, evokes, draws forth a complex set of molecular responses that may superficially look like foresight, intelligence, a master Molecular Biologist tinkering with the genes; but in fact all that is happening is mutation and reproduction, interacting with a changing external environment.