Shadows of Forgotten Ancestors

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: … TACCAGCTAG …

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 (CC, say) and replace it with an unimpaired sequence (CTTC). Protecting the genetic information and making sure it can reproduce itself with high fidelity is a matter of the highest priority. Otherwise, useful sequences, tried-and-true instructions, essential for the adaptation of organism to environment, may be quickly lost by random mutation. Proofreading and repair enzymes correct damage to the DNA from many causes, not just UV light. They probably evolved very early, at a time before ozone, when solar ultraviolet radiation was a major hazard to life on Earth. Early on, the rescue squads themselves must have undergone fierce competitive evolution. Today, up to a certain level of irradiation and exposure to chemical poisons, they work extremely well.