12 Reasons Our Genes Can’t Control Us
Genetic sequences are vitally important for life, but why? Our theory of life may have been built on an unproven assumption. We have supposed that the genetic material in cells, the genome, is a list of instructions. This assumption has held since the discovery of DNA in the mid-twentieth century, but now there may be another, largely unexplored way to interpret the role of the genome. Is there a coherent view of biology other than that of The Selfish Gene? A scattered group of thinkers may be suggesting another way forward. Lynn Margulis, Peter Godfrey-Smith, Michael Skinner, James Shapiro, Eva Jablonka, Marion Lamb, Michael Levin, and Denis Noble have all suggested various deep revisions of the idea that randomly mutating “selfish” genes contain instructions for life. In this essay I will try to unite some of these objections into a possible alternative hypothesis.
There are several reasons we might suppose that the coding regions of DNA sequence (genes) don’t carry instructions at all. Instead, they may be just lists of templates for proteins that can be produced by the cell, if the cell chooses to do so. They could be like tools in a toolbox. The instructions that control which tools to use, and when, could possibly come from the environment around the individual cells and around organisms. This envelope of surrounding influences may be what tells all organisms what goals to pursue and what to become.
This idea may provide a new way to interpret the formation of biological selves and cellular goal-seeking, and could shed light on the still-murky definition of intelligence. Some philosophers to be the current roadblock to the development of genuine “thinking” AI is our lack of a fundamental theory of intelligence.
There are twelve major reasons this may be the right way to interpret cell biology:
First, we have discovered that all cells in our bodies carry the same DNA even though there are 200 or more cell-types and they perform vastly different functions. Cells in large organisms like humans differentiate into myriad structures like bones, muscles, immune systems, neurons, and so on. This happens not because they carry different genetic sequences, but because different cellular environments during development cause different patterns of gene expression, making them diverge from a single pluripotent stem cell zygote into distinct tissues.
Second, we have discovered that cells in the same tissue express a given gene at markedly variable rates, with as much as 1000-fold difference between two adjacent cells. Gene expression is stochastic at a small scale, and yet overall function is stable at a large scale. Organs function reliably, even while cells carry out their individual functions in highly variable ways. This result suggests that gene expression is determined by exterior conditions, which are variable from cell to cell, rather than the genetic sequence, which is an invariant molecule present in the nucleus of every cell.
Third, we have discovered that the majority of genetic protein-coding sequences are likely to have no effect on phenotype by themselves under normal conditions. Gene knockout experiments often find extensive genetic buffering. In a study done by Hillenmeyer et al. in 2008 (The chemical genomic portrait of yeast) published in Science, over 80% of coding sequences silenced had no visible effect on the resulting organism. If the genome were instructional, this result would be puzzling. How could 80% of deleted vital instructions have no effect? If, however, the genome were a toolbox, then the possible redundancy and irrelevance to function of particular sections of DNA would be unproblematic.
Fourth, except in a few cases of rare genetic disorders, traits usually do not correspond to particular genes. Genome wide association studies that look for strong correlations between complex traits and specific genetic material almost invariably fail to replicate. Without these strong correlations, it is hard to see random mutation and natural selection could drive the change in phenotypes. The problem that traits correspond only very loosely with inherited genotypes is called the missing heritability problem. This problem is made more severe by the hypothesis that all genes are involved in complex traits. The Human Genome Project was hyped as a profound breakthrough for medicine, because it was predicted that knowing their genetic code would predict 80% or more of a human’s traits. But in truth, even the founders of these projects admitted some disappointment. Genetics is causally interrelated with all disease simply because all life requires proteins. But these studies show that the genetic code does not accurately predict the way that genes are interpreted to produce phenotypes.
Fifth, experiments have been done to demonstrate that the cell does indeed have a large impact on development. For example, in a 2005 study of cross-species cloning, the a common carp nucleus was transplanted into a goldfish recipient egg. The resulting fish had a vertebral column more closely resembling the cytoplasmic recipient than the nuclear donor. This demonstrates that the cell does contribute to development, thus phenotype cannot be explained by genetic sequences and environment alone.
Sixth, we have discovered that transgenerational epigenetic inheritance (TEI) is widespread in nature. If the instructions were in the genome, inherited epigenetic changes would degrade those instructions and quickly make them useless for maintaining life. It would be like a game of “telephone,” where intended messages quickly drift into nonsense. Even one genuine case of this would be sufficient to disprove the idea that the instructions for all life are contained exclusively in the genome. Yet examples of TEI have been found in complex model organisms across the tree of life, including humans. In plants, for example, somatic cells can give rise to new germline cells, thereby passing along any epigenetic changes they have acquired. In single-celled life it would be impossible for TEI not to occur in every lineage, since the entire parent cell structure is inherited by the daughter cells. There are complex, multicellular animals with nervous systems, planaria for instance, that reproduce from fission indefinitely, thereby avoiding any step in inheritance that reprograms all the cells by removing epigenetic marks. These examples are plain disproof for the idea of genetic instructions.
Seventh, there is a clear mechanism for epigenetic changes to shape the form of the genome. This mechanism is known as “genetic assimilation,” and was discovered by the biologist Conrad Waddington in the 1950s. Genetic assimilation happens when an organism first adopts a phenotype through epigenetic alterations, and then genetic change through natural selection reinforces or “canalizes” this change. By persisting in the lifestyle that the epigenetic changes permit, the organism causes the selection pressures that favor its new phenotype. This mechanism allows the phenotype to change the genotype even without specifying particular molecular genetic sequences. The Central Dogma specifies that information only travels from DNA to protein and not back again. But Waddington’s mechanism transfers information to the genome without violating the prohibition against reverse translation from protein to DNA.
Eighth, there is a step in sexual reproduction called “crossing over” where the genetic material on each chromosome is cut and spliced independently to form a new combination of genetic material. This recombination does not respect any particular boundaries, ensuring that no sequence of genetic material can truly form an indivisible replicator. This means that sections of DNA are not, in themselves, units of Darwinian selection.
Ninth, it is now widely acknowledged that many organisms engage in niche construction, changing their environment to enable their lifestyles and reducing selection pressures that might force them to evolve different strategies. They can also directly inherit functional behaviors from their parents outside of reproductive channels by imprinting, as was demonstrated in a recent study of rat maternal licking. These biases are not accounted for in traditional evolutionary theory.
Tenth, we have discovered that the human gut microbiome is a self-organizing functional system akin to an organ. This microbial community is not inherited but largely acquired after birth. It forms in the human digestive tract out of foreign cells with foreign DNA. These communities change with diet, age, and other factors, yet the combination of bacterial taxonomic lineages remain as unique for each individual as a fingerprint. Despite thus containing totally divergent sets of nonhuman genetic material, these communities contribute to cognition, metabolism, immune function, and digestion. Health conditions causally attributed to imbalances in these communities can be every bit as serious as imbalances in somatic human cells.
Eleventh, we now know that organisms that become less likely to die as they get older can have roughly the same number of genes as organisms that age rapidly. Take for example oak trees (genus Quercus) and octopuses (genus Octopus). The genomes of organisms in each genus contain roughly the same number of protein coding sequences, yet oaks can often live for hundreds of years while octopuses senesce in as little as one year. The best gene-centered explanation for senescence is the idea of antagonistic pleiotropy. This concept argues that since selection occurs on genes for beneficial effects on reproduction, genes that have a beneficial effect on young, reproductive organisms while causing deleterious effects on older organisms will be favored by natural selection. But this fails to explain why genes cannot, as in the case of the oak, favor reproductively successful older organisms, rather than, as in the octopus, degrading function quickly after reproduction. Some organisms, like certain jellyfish, age in reverse rather than senescing. These examples show that antagonistic pleiotropy is more likely to be an effect of lifespans rather than the cause. If genes are tools of the environment rather than causal instructions, it leaves open the possibility that epigenetic changes that improve function, i.e. intelligent learning, explain the evolutionary fitness of rapidly senescing adaptive phenotypes in creatures like the Octopus genus.
Twelfth, we have discovered that the fossil record shows not steady change based on random mutation but punctuated equilibrium. If genetic sequences were the instructional basis for life, then we would expect that organisms would have changed relatively steadily as random mutations accumulated in their genes. Organisms have not changed steadily over geologic time; instead the fossil record shows long period of relative stasis interspersed by short periods of rapid evolution. There are bursts of creativity, such as the period known as the “Cambrian explosion” when the precursors to many of the major surviving groups of life forms first appeared. This evidence points to another, perhaps unknown mechanism, that underpins evolutionary processes beyond purely random genetic mutation.
If the genetic sequence is considered the instructions for life then all of these results, and others, remain poorly explained. However, if an organism turns out to be a process that can be instructed by its surroundings, these results are unproblematic. How this mechanism could work is still a complete mystery. My term for this undiscovered mechanism is “epistolution,” because it would unite epistemology, the sources of intelligent knowledge, with evolution, the sources of organic change. If correct, this idea would mean that organisms are conducting a blind search for knowledge during their lifetimes by changing their cellular mechanisms based on their surroundings. This would mean that organisms are composed of some unknown units that can be filtered somehow by the environment during active life, perhaps according to use and disuse, resulting in configurations with increasing adaptive function.
There is no doubt that at least one species of organism, Homo sapiens, is intelligent and creative. Biologists are also discovering much more about the adaptive learning capacities of other species. Crows, for example, can solve puzzles that five-year old children cannot solve. Dolphin and orca pods form distinct hunting cultures and communicate with songs that might resemble pre-human vocalizations. These capacities continue to make it harder to consider humans totally unique in our ability to learn and create knowledge in some form. Learning of any sort constitutes non-random change, instructed by the environment. These adaptive behaviors are not independent of evolutionary forces. All behaviors influence the context in which natural selection occurs. If they play a role in natural selection, they must also logically play a role in shaping the genome. Genetic change, then, could not be a process that is isolated from the unknown mechanism of intelligence.
There is currently no consensus definition of intelligence or creativity, and no scientific agreement on how far it reaches into the tree of life. Since we do not have a plausible theory for how intelligence arises from groups of cells and we cannot build an intelligent being from non-living materials, we cannot rule out the possibility that intelligence is present in all life forms to some degree. If this is a possibility, then there is also a possibility that it is a version of intelligence present in all cells that results in functional gene expression.
Nothing could have been naturally selected until it was first self-organizing and reproductive. It is therefore a circular argument to hold that self-organization and reproduction are entirely explained by the natural selection of DNA. Another, perhaps unknown, process is required. This mystery is an inspiring provocation to re-examine the natural world.
