Evolution in four dimensions

It has been estimated that in the human genome at most 1.5 percent of the DNA codes for proteins. A little codes for tRNAs and other nontranslated RNAs, but most of it is never or hardly ever transcribed, let alone translated. So what role does it play?

... a lot of DNA has no obvious function, and it is commonly regarded as "junk". However, some nontranscribed sequences certainly do have a function --- they are involved in the regulation of gene activity. Not every gene is active in every cell all the time. This is why cells can be different, even though most of them have the same set of genes. Cells are able to respond to respond to internal and external conditions, turning genes on and off when and if required, and nontranscribed DNA is an important part of the regulatory system that determines which coding sequences are being transcribed. (p. 52)

These two characteristics of DNA --- the vast number of variations possible because of its modular organizations, and the indifference of the replication process to the "content" of the transcribed sequence --- mean that potentially it can provide a lot of raw materials for natural selection. But these same characteristics have a downside: they also mean that a lot of nonsensical variations can be generated and transmitted. One of the questions that immediately arise, therefore, is how organisms cope with potentially vast number of frequently useless or detrimental variations. If the quality of information can be tested only through its functional effect in the next generation, it seems to be a terribly wasteful system. In fact, as we shall see later, some of the most ingenious mechanisms in living organisms are direct or indirect solutions to the problem of DNA's potential to vary. In addition, the way in which DNA is actually "interpreted" in the context of a developing organism makes the problem far less formidable than it seems at first glance. (P. 56)

Children who are born second, third, or later in the family are more adventurous than first born or only children are. (p. 60)

Comment: I can understand it intuitively. Think if we can derive it mathematically.

Geneticists started using genetic engineering techniques to "knock out" (disable) a particular gene and follow the consequences of this knock out on development. Much to their surprise, the scientist found out that knocking out genes that were known to participate in important development pathways often make no difference whatsoever --- the final phenotype remained the same. ... Knockout experiment shows that there is a lot of structural and functional redundancy in the genome... The evolved network of interactions that underlies the development and maintenance of every character is able to accommodate or compensate for many genetic variations. This is why so many of the potentially deleterious effects of the huge number of variations in the information in DNA are masked and neutralized. (p. 65)

Comment: The redundancy of genes can be used to support the regulation, such as antitrust and anti monopoly, which may make business less efficient but more stable.

Most evolutionists would agree that in the short term, asexual reproduction, which preserves the parent's well-adapted combination of genes, is best. The snag is that parental genomes cannot be preserved for ever. Even totally asexual lineages change, because mutations are inevitable. Some harm their carriers, and will be weeded out by natural selection, but many may remain and accumulate. Consequently, in the long run, asexual lineages may deteriorate and go extinct. In contrast, if organisms reproduce sexually, the shuffling and recombination of parental genes means that some offspring may be lucky and get dealt a set of genes with fewer damaging mutations than either of their parents. Sexual reproduction can therefore preserve lineages by preventing the accumulation of deleterious mutations. Another advantage is that competition for resource is intense, then at least some sexually reproduced offspring may have genotypes that make them good competitors. In the medium to long term, in changing environments, by bringing together beneficial mutations arising in different individuals, sex will lead to faster evolution than would be possible in asexual lineages. (P. 82)

However at least some of them are thought to be adaptations that determine how much genetic variability there is in the next generation. Take the species that have both sexual and asexual generations: generally, they reproduce asexually when conditions are constant and good. but sexually when things change or life becomes stressful. Aphids, for example, commonly reproduce asexually throughout the summer, but before they overwinter, they have a sexual generation. Similarly, Daphnia, the water flea, reproduce asexually when environmental conditions are good, but when life gets tough it switches to sexual reproduction and produces resistant eggs that can survive poor conditions. This makes evolutionary sense. If an individual is doing well and its environment is not changing, asexual offspring, who have the same set of genes, will probably do very well too. So why change? If it ain't broke, don't fixed it! ...But if conditions change, so that offspring are likely to experience a different environment, ... investing in sexual reproduction is a better bet. Although costly males have to be produced, at least a few of the varied sexual offspring may survive new conditions. ...

There is some evidence that another aspect of sexual reproduction, the amount of crossing-over between chromosomes, has also evolved to fit the conditions of life. It tends to be lower for species living in uniform, stable environment, and higher for those living where conditions are less predictable. The suggested explanation is that natural selection has led to low recombination rates in constant conditions, because offspring do best if they have much the same genotype as their parents. But when lineages have repeated encountered varied or varying conditions, high recombination rates have been selected, because variety among the offspring has increased the chances that some will survive. We know from laboratory experiments that the average rate of recombination differs between populations of the same species, and that selection can change recombination rates. We even know some of the genes and alleles that affect recombination. So, although the evidence that average recombination rates are related to ecological conditions and the lifestyle of the species is not extensive, it would be surprising if the rate of recombination had not been adjusted by natural selection. (p. 85)

Long-term Darwinian evolution through the genetic system depends on these DNA changes. But there is a paradox here, because DNA is changeable, its effectiveness as the carrier of hereditary information is reduced. If only very imperfect copies of the information that has enabled survival and reproduction are transmitted, evolution by natural selection will be very slow, if not impossible. Information needs to be durable, as well as somewhat changeable. So how can DNA, which is not an intrinsically stable molecule, function so effectively as a carrier and transmitter of information?

The answer is that DNA can do its job because organisms have a whole battery of mechanisms that protect and repair it, ensuring that existing nucleotide sequences are well maintained and are copied accurately. Cells have proteins that scavenge for and degrade molecules that would damage DNA; if damage does occur, there is another set of proteins that can repair it, sometimes using a recombination process that substitutes a similar undamaged sequence from elsewhere. When DNA is replicated, there are systems that check that each nucleotide added to the growing daughter strand is the correct (complementary) one, and remove it if it is not. After the new daughter strand is synthesized, it is proof read, and if mismatched nucleotides are found, they are corrected. Thanks to these and other proofreading and correction systems, the error rate during the replication of human DNA is only about one in every ten thousand million nucleotides. Without them, it has been estimated it would be nearer one in a hundred.

This amazing system for maintaining the integrity of DNA has presumably evolved through natural selection for DNA-caretaker genes. Lineage with poor DNA maintenance and sloppy replication failed to survive, because they kept changing, producing all sorts of mutations, most of which were detrimental. Such lineages had a lot of variation, ut less heridity; good sets of genes were not transmitted accurately. Lineages with better mechanisms for looking after their DNA continued, because they transmitted accurate copies of the genes that had allowed them to survive and reproduce. In this way, natural selection has ensured that there is a good genetic engineering kit for DNA maintenance, and that mutation rates are generally low. (p. 87)

In the future, attention undoubtedly will be centered on the genome, with greater appreciation of its significance as a highly sensitive organ of the cell that monitors genomic activities and corrects common errors, senses unusual and unexpected events, and responds to them, often by restructuring the genome. (McClintock, 1984, p. 800)

We now know that stress conditions can affect the operation of enzyme systems that are responsible for maintaining and repairing DNA, and parts of these systems sometimes seem to be coupled with regulatory elements that control how, how much and when DNA is altered. (p. 89)

Comment: We may explain this as when resources are reduced or uncertainty increases, fixed cost, which means the cost to maintain the operation of enzyme systems, decreases.

With local mutation, there is a measure of randomness in what is produced, but this randomness is targeted or channeled, because the changes occur at specific genomic sites and sometimes in particular conditions. (p. 101)

Even if we didn't have all the new experimental evidence showing that mutation is sometimes localized and under environmental or developmental control, the evolutionary arguments for expecting it are very powerful. It would be very strange indeed to believe that everything in the living world is the product of evolution except one thing --- the process of generating new variation! No one doubts that how, where and when organisms use sex, which reshuffles existing genetic variation, has been molded by natural selection, so surely similar selection pressures should also influence how, when and where variation is generated by mutation. In fact it is not difficult to imagine how a mutation generating system that makes informed guesses about what will be useful would be favored by natural selection. In our judgment, the idea that there has been selection for the ability to make an educated guess is plausible, predictable and validated by experiments. As the American geneticist Lynn Caporale has said, "chance favors the prepared genome." (p. 101)

The function of prion shows that protein can act as a genetic material as well. It can replicate proteins modeling after itself. See p. 123 -126.

Epigenetic marks affect not only gene activity, they also affect the probability that the region will undergo genetic change. Mutation, recombination, and the movement of jumping genes are all influenced by the state of chromatin, so the likelihood of a genetic change in two identical pieces of DNA is not the same if they have different chromatin marks. In general, DNA is more likely to change in regions where the chromatin is less condensed and genes are active than it is in more compact regions. That's because in active regions DNA is more accessible to chemical mutagens and to the enzymes involved in repair and recombination. It's not unlike what happens with your car, which is more exposed to accidental damage and change when you drive it around than it is when kept parked in the garage. There are exceptions of course. Just as dead batteries may be more common in cars that are permanently garaged, so some types of DNA change are more common in inactive genes. For example, the base cytosine (C) mutates to thymine (T) more frequently when it is methylated than when it is not, and methylated DNA is usually associated with compact chromatin and inactive genes. Nevertheless, the overall picture is that DNA in the regions where genes are active is more likely to change than that in active domains.

We now have to ask whether the influence that chromatin structure has on the likelihood of genetic changes is of any significance in development and evolution. ...There are some very telling indications that it may be very important. For example, there is an increasing amount of data suggesting that there is an interplay between genetics and epigenetics in the development of cancer. The first sign of cellular abnormality in some tumors is an epimutation --- a change of heritable chromatin marks, such as an increase or decrease in the density of DNA methylation. Commonly, genetic changes seem to follow epigenetic ones. (p. 248)

Contrary to current dogma, the variation on which natural selection acts is not always random in origin or blind to function: new heritable variation can arise in response to the conditions of life. Variation is often targeted, in the sense that it preferentially affects functions or activities that can make organisms better adapted to the environment in which they live. Variation is also constructed, in the sense that, whatever their origin, which variants are inherited and what final form they assume depend on various "filtering" and "editing" processes that occur before and during transmission. (p. 319)

Obviously, since most mutations are likely to make things worse rather than better, it would be much more efficient if the extra mutations induced by stressful conditions were restricted to those genes that, if changed, could rescue the cell. And we know that there are situations where cells do produce mutations not only at the right time but also at the right place. ... the bacterium E. coli can sometimes make very appropriate mutational guesses. ... when starved of a particular amino acid, the bacteria increased the mutational rate in the very gene that might, if mutated, enable the cell to make the amino acid missing from its food. (p. 322)

It is even easier to imagine how another of our categories of interpretive mutations evolved by natural selection. This is the one that is often found in pathogenic microorganisms, where there is a consistent high rate of genetic change in certain restricted regions of genome. In these "hot spots", mutation is going on all the time at a rate hundreds of times faster than elsewhere. This is not the disaster it would be at other sites in the genome, because genes in hot spots code for products that need to change frequently. Think, for example, pathogenic organism that is constantly at war with its host's immune system. The immune system recognizes the pathogen by its protein coat. The pathogen can evade detection for awhile if it changes its coat, but the host's immune system will soon catch up, and recognize the new coat. Yet another coat is needed. The pathogen has to constantly keep one step ahead of its host's defenses. If its coat protein genes are the mutational hot spots, then there is a good chance that it will be able to do so. (p. 323)