Modern biology has been dominated by three revolutions. The first was initiated by Mendel, who founded modern genetics, the second by Darwin, who investigated the mechanism of evolution and the last by Watson-Crick. The Watson-Crick era began as a paradigm of the function of the gene. The theory of the information stored in the double-stranded DNA of the gene and translated into proteins evolved unfortunately and mistakenly into a paradigm of Life. The most vocal defender of the molecular form of gene determinism is probably Monod9. According to him, an understanding of how genes code for proteins also explains how genes cause cancer, tuberculosis or alcoholism. The mistaken idea is that complex behavior may be traced solely to genetic agents and their surrogate proteins. This illegitimate extension of a genetic paradigm from a simple level of genetic coding to a complex level of behavior represents an epistemological error of the first order. Yet, the present-day consensus around gene determinism is powerful. As a paradigm, it promises molecular diagnosis and therapy for literally every possible ailment or disorder, ranging from flu to paranoia. As a result, we learn more and more about mechanisms and less and less about life. Ultimately, paradigmatic anomalies accumulate, and show up almost weekly in journals of molecular biology. If genomes are the books of life, then genes are the words that tell the story of each organism of every known species. It is currently assumed that microorganisms are short stories and complex mammalian organisms are great tomes. This is not true. The fruitfly has some 5000 fewer genes than the supposedly much simpler nematode worm.
A hot debate has taken place about the number of genes composing the human genome. It was argued that human complexity couldn’t be explained by any other way than by inflation of genes, estimated to be around 140,000. However, organizational complexity and intelligence are not related to gene number but to gene regulation and expression. It is now certain that the human genome contains some 35,000 individual genes, which code for more than 160,000 proteins, many of which are modified after their synthesis, before exerting their biological function. The sequence of a particular gene only establishes the sequence of the amino acids of a protein. It gives no information about the biological function of that protein, which may be modified (addition of sugars and lipid residues, modification of the configuration in space of that protein) after its synthesis.
We face two problems. The first one is the “analytical chemist” syndrome that poisons the minds of most Life scientists and medical regulatory agencies. The preoccupation with purified molecules for the study of protein structure and function –legitimate in early days, when the goal was to isolate the various substances included in a biological structure- is a major drawback in our current understanding of protein function. Life does not involve isolated proteins. These exist only in the test tubes of the biochemistry laboratory. In real life, proteins exist in complexes: they are multi-component systems. The second problem is our lack of understanding of protein folding. Examples may be produced, in which little correlation exists between genetic and morphological complexity. Human and chimp DNA is homologous at 98 to 99% 10 and yet these two species manage to construct very different results from these nearly identical genes. Other species are quite similar in their morphological patterns, yet very dissimilar at the level of their genes (for example sharks and dolphins, opossums and rats). Mice and humans have the same number of expressed genes, yet, even if most molecules are identical, one may not claim that mice and humans are identical. Sooner or later, the paradigm of genetic determinism will crumble11. One of the basic rules of Mendelian genetics is that all chromosomes are created equal. The laws of probability of Mendel have been found to be circumvented at the level of the spermatozoid. In a diploid cell carrying a pair of chromosomes, a mutated gene may play no role, the activity of the normal gene being sufficient to fulfill the needs of the organism. However, in haploid spermatozoids, the two genes are located in two different cells. Each spermatozoid carries only one variety of the two genes available in paired genes. Mutations may occur on one gene, borne by one chromosome, and not affect the paired gene located on the other chromosome of the pair. Yet, spermatozoids are alive. They have a metabolism. The mutated gene may enhance the survival potential of the spermatozoid that bears it, may favor its mobility, and this spermatozoid has an increased chance to engage in the fertilization of an egg. The laws of probability of Mendel are thereby bypassed.
Moreover, normal genes may themselves regulate the activity of spermatozoids. It has been observed in mice since the 1930s that sometimes one chromosomal partner involved in sexual reproduction consistently wins over the other. This is because a gene alters the ability of mature sperm to swim to the egg by causing the flagella of the sperm to beat too slowly while other genes cause them to beat much too fast. Only the sperm that possesses both genes together moves optimally. There exist genes, at least in flies and mice, that promote their own inheritance, and such genes probably are at work also in people.
The latest blow to gene determinism and chance mutations is that the genome has the ability to make much larger changes than simple point mutations, and that organisms have evolved the ability to modulate the rate, location and extent of genetic variation. There occur changes in genetic expression that are not linked to alterations in DNA sequences. These epigenetic changes may sometimes be passed on to offspring in ways that violate Mendelian genetics, and could play a role in evolution, especially in plants. Plants produce their germ cells very late in their life cycle, which does not efficaciously shield them from the epigenetic modifications to which mature plants are exposed. If Lamarck’s global view of evolution, based on the heredity of traits acquired by parents during their adult life, is not correct, the discovery of epigenetic changes have helped restore him to his rightful place in scientific history.
Our evolutionary theory is incomplete. The rule of brain formation, which is the key evolutive trend of the chordates, is not reducible to the rules of genetic determinism. The driving force of evolution cannot be located solely in random mutations. It is now clear that DNA alone cannot contain sufficient information to determine how proteins interact to produce a mechanism, i.e. a specific species. Each higher level of organization has its own rules and there is no gradual transition from one level to the next. Yet, nothing is there to replace the current paradigm: if genes do not determine us, what does? Since a normally constituted scientist cannot remain a scientist and, at the same time, reject the paradigm under which his work is done, there is no answer to the question and we go on repairing a defective genetic paradigm that looks for answers in simple genetic programs. We try to fit dynamic non-linear change into a linear theory of the gene, and are astonished that it does not fit.
10. This is broadly speaking true but false when the DNA is analyzed in detail. At close inspection, there are modifications in the set up of the genome that split the human and chimp genome by more than 2%.