Chapter 115 19.4 Premises for nonrandom mutation

Natural selection is the grim death of nature.Darwin boldly claimed that, at the very heart of evolution, many mass-deleted insignificant parts—many insignificant random deaths—whose mere momentary pleasure in slight changes can, in counterintuitive ways, add up to genuine novelty and valuable product.In the drama of traditional choice theory, death plays the leading role.It's single-mindedly cutting down on life.It's an editor, but with one word: "No."Mutation easily rivals the one-note burial of Death by spawning a mass of new life.Variation also has only one word: "maybe".Mutation creates a large number of one-off "possibles", and death destroys these "possibles" in large numbers at once.Most mediocre talents are sent back by wanton death as soon as they come into the world.Sometimes, the theory goes like this: the duet utters a note: "Yes!"—so the starfish stays, the kidney cells split, and Mozart survives.On the face of it, evolution driven by natural selection is still an amazing hypothesis.

Death purged the impotent to make room for the new.But it is a fundamental mistake to say that death causes the formation of wings and the operation of eyeballs.Natural selection just picked out those misshapen wings or those blind eyes.Lynn Margulies said, "Natural selection is the editor, not the author".So, what is it that created and invented the ability to fly and the ability to see? Evolutionary theories since Darwin have had a rather bleak record on the origins of the original innovations in the evolutionary process.As the title of Darwin's book makes clear, the questions he wished to solve were the great puzzles of the origin of species, not the origin of individuals.He asked: Where did the new species of life come from?But it doesn't ask: Where does the variation between individuals come from?

Genetics began as a distinct and separate field of science that did focus on the origins of variation and innovation.Early geneticists, such as Mendel, William Bateson (father of Gregory Bateson, who coined the word "genetics" - genetics -), in order to explain how differences in individuals and how mutations are passed on to future generations.Sir Galton demonstrated that from a statistical perspective—statistics was a dominant approach in genetics before the advent of bioengineering—the inheritance of variation within a population can be considered to arise from some random source.

Later, scientists discovered the genetic mechanism in a long chain of molecules encoded by four symbols. The random flipping of symbols at a random point in this long chain can easily be imagined as a cause of variation, and it is also easy Build mathematical models.These random movements of molecules are generally attributed to cosmic rays or some kind of thermodynamic perturbation.From a new perspective, the odd-looking mutation that once meant severe deformity was nothing more than a flip away from the average mutation.Not so long ago, all trait variations that occurred in an organism—from freckles to cleft palate—were considered to be statistically variable in varying degrees.Therefore, the mutation becomes a mutation, and the "mutation" follows the machine to form an inseparable "random mutation".Even the term "random mutation" seems a bit redundant these days. — Besides random mutations, are there other types of mutations?

In computer-enhanced artificial evolution experiments, mutations are generated electronically, known as pseudo-random generators.However, the exact facts of the origin of mutation and variation in the biological world remain uncertain.What we do know is this: Clearly, variation does not arise by random mutation—at least not always; there is some degree of order in variation.This is an old idea.As early as 1926, Smuts had a name for this genetic semi-order: intrinsic selection. A plausible description of this "intrinsic selection" is that cosmic rays are allowed to produce random errors in the DNA code, and then some known self-healing mechanism, in a discriminative (but unknown) These errors are corrected in the cells - correcting some errors while letting others go.Correcting errors requires a lot of energy, so a balance needs to be made between the energy consumption required to correct errors and the possible benefits of mutation.If the error occurs where it might be opportune, the error correction mechanism will let it stay, and if it occurs where it will cause trouble, it will be corrected.To give a hypothetical example: The Krebs cycle is the basic energy factory of every cell in your body.It has worked well for hundreds of millions of years.Therefore, if you mess with it, you will lose more than you gain.At this time, if the body detects that there is a mutation in the Krebs cycle code, it will quickly eliminate it.On the other hand, the size of the body, or the proportions of its parts, might be worth tweaking; then, let the mutations do the trick.If this is how intrinsic selection works, then differential variation means that some random variations are "better favored" than others.Not only that, but a fascinating consequence of this tuning is that mutations in the regulatory machinery itself can have far greater large-scale effects than mutations in the strands of DNA it regulates.I'll come back to this later.

There are very extensive interactions and mutual regulatory relationships between genes, so that the genome forms a complex whole that resists change.Because genes are largely interdependent, so closely related—almost interlocked—that variation is not an option, variation is only possible in a few specific areas.As the evolutionist Ernst Meyer said: "Free variation can only be seen in a limited part of the genotype." The overall power of this inheritance can be seen in the process of human domestication of animals.Breeders often face the dilemma that in the process of selecting for a specific trait, some unknown genes are activated at the same time, resulting in undesirable side effects.However, when those environmental pressures on the trait were relaxed, subsequent generations of the organism quickly reverted to the original trait, as if the genome had sprung back to square one.The variation in the real gene is far from what we imagined.This is an indication that variation is not only nonrandom and limited in scope, but also simply hard to obtain.

One gets the impression that there is a highly flexible genetic bureaucracy that manages the lives of other genes.Most amazingly, all life, from fruit flies to whales, is empowered by the same genetic authority.For example, almost identical homeobox autoregulation sequences (a master switch gene that turns on large stretches of other genes) are found in every vertebrate. This logic of non-random mutation is so popular now that I was initially surprised to find that I couldn't find any mainstream scholars who still held the view of random mutation.They conceded, almost unanimously, that mutations "are not truly random."What this means to them is that (as far as I feel) individual mutations may not be so random—only near or seemingly random.Still, they believe that, given enough time, a large number of mutations will appear random in a statistical sense.Lynn Margulies sarcastically said: "Oh, the so-called randomness is just an excuse for ignorance."

Today, this weakened view of non-random mutation is less controversial, and the stronger version is a provocative heresy.The idea is that mutations can be selected for in some deliberate, deliberate way.Rather than saying that the Genetic Authority only edits random mutations, it is better to say that it generates mutations itself according to some schedule.Genomes create mutations for specific purposes.Directed mutation can stimulate the blind process of natural selection, taking it out of the mire and pushing it into states of increasing complexity.In a sense, organisms self-program and export mutations in response to environmental factors.Somewhat ironically, this strong view of directed mutation has more evidence in the laboratory than the weakened nonrandom view.

According to the laws of neo-Darwinism, the environment, and only the environment, can select for mutations; moreover, the environment can never induce or direct mutations. In 1988, Harvard geneticist John Cairns and his colleagues published evidence that E. coli was mutated by environmental influences.Their assertion was bold: Under certain conditions, the bacteria spontaneously produced the desired mutations in direct response to environmental stress.Not only that, but Keynes had the audacity to end his thesis by stating that whatever caused the directed mutation "provides, in effect, a mechanism of acquired inheritance"—this is simply Lamarck's stark Darwinian counterpart. View.

Another molecular biologist, Barry Hall, published research results that not only confirmed Keynes' assertion, but also supplemented the surprising evidence of directed mutation in nature.Hall found that the E. coli he cultivated not only produced the desired mutations, but also mutated at a rate about 100 million times higher than would be expected statistically according to random theory.More than that, when he sequenced the genes of these mutant bacteria and isolated them, he found that only those areas under selective pressure were mutated.This means that these successful little ones didn't desperately play all the mutation cards to find the one that worked;Hall found that some directed mutations were so complex that they required mutations in two genes at the same time.He called it "the very improbable of the very unlikely."These miraculous changes should not be the result of a series of random accumulations under natural selection.They (directed mutations) carry a certain taste of design.

Both Hall and Keynes claimed to have carefully ruled out other possible explanations for the results, insisting that the bacteria were directing their own mutations.But few other molecular geneticists are prepared to abandon rigorous Darwinian theory until they can elucidate how ignorant bacteria figure out which mutations they need.