2400 words

A mutation can be said to be directed if it arises due to the needs of the developing organism, and they occur at higher frequencies if it is beneficial (Foster, 2000; Saier et al, 2017). If there is some sort of stress, then an adaptive mutation would occur. The existence of this kind of mechanism has been debated in the literature, but its existence spells trouble for neo-Darwinian theory, whose proponents claim that mutations are random and then “selected-for” in virtue of their contributions to fitness. Indeed, this concept challenges a core tenet of neo-Darwinism (Sarkar, 1991). I will argue that directed mutation/non-random mutation/stress-directed adaptation (DM, directed mutation for short) spells trouble for the neo-Darwinian paradigm.

The issue at hand

The possibility of DMs were argued for by Cairns, Overbaugh, and Miller (1988), where they argue that environmental pressure can cause adaptive changes to genes that would be beneficial to the organism. This then spurred a long debate about whether or not such mutations were possible (see Sarkar, 1991; Fox Keller, 1992; Brisson, 2003; Jablonka and Lamb, 2014). Although Cairns, Overbaugh, and Miller were wrong—that is, they were not dealing with mutations that were due to the environmental disturbances they posed (Jablonka and Lamb, 2014: 84)—their paper did bring up the possibility that some mutations could be a direct consequence of environmental disturbances which would then be catapulted by the homeodynamic physiology of the organism.

Saier et al (2017) state the specific issue with DM and its existence:

Recently, strong support for directed mutation has emerged, not for point mutations as independently proposed by Cairns, Hall and their collaborators, but for transposon-mediated mutations (12, 13). If accepted by the scientific community, this concept could advance (or revise) our perception of evolution, allowing increased rates of mutational change in times of need. But this concept goes against the current dogma that states that mutations occur randomly, and only the beneficial ones are selected for (14, 15). The concept of directed mutation, if established, would require the reversal of a long accepted precept.

This is similar to the concept of phenotypic plasticity. It is the phenomenon of a given genotype expressing different phenotypes due to environmental factors. This concept is basically a physiological one. When talking about how plastic a phenotype is, its relation to the physiology of the organism is paramount. We know that physiological changes are homeodynamic. That is, changes in physiology are constantly happening due to the effects of the environment the organism finds itself in. For example, acute changes in heart rate occur due to what happens in the environment, like say a predator chase it’s prey. The heart rates of both predator and prey increases as blood flow increases due to stress hormones. I will discuss phenotypic plasticity on its own in the future, but for now I will just note that genetic and environmental factors influence the plasticity of phenotypes (Ledon-Rettig and Ragsdale, 2021) and that phenotypic plasticity and development play a role in evolution (West-Eberhard, 2003, 2005; Wund, 2015

The fact of the matter is, phenotypic plasticity is directly related to the concept of directed mutation, due to DM being a largely physiological concept. I will argue that this refutes a central Darwinian premise. Namely that since directed mutations are possible, then they are not random. If they are not random, then due to what occurs during the development of an organism, a directed mutation could be adaptive. This, then, is the answer to how phenotypic traits become fixed in the genome without the need for natural selection.

Directed mutations

Sueoka (1988) showed that basically all organisms are subject to directed mutations. It has been noted by mathematicans that on a purely random mutational model, that there would not be enough time to explain all of the phenotypic diversity we see today (Wright, 2000). Doubt is placed on three principles of neo-Darwinism: mutations occur independently of the environment the organism is in (this is empirically false); mutations are due to replication errors (this is true, but not always the case) and mutation rates are constant (Brisson, 2003).

One of the main claims of the neo-Darwinian paradigm is that mutations occur at random, and the mutation is selected-for or against based on its relationship to fitness. Fodor’s argument has refuted the concept of natural selection, since “selection-for” is an intensional context and so can’t distinguish between correlated traits. However, we know now that since physiology is sensitive to the environment, and since adaptive changes to physiology would occur not only in an organism but during its development, it then follows that directed mutations would be a thing, and so they wouldn’t be random as neo-Darwinian dogma would claim.

In her review Stress-directed adaptive mutations and evolution, Wright (2004) concludes:

In nature, where cell division must often be negligible as a result of multiple adverse conditions, beneficial mutations for evolution can arise in specific response to stressors that target related genes for derepression. Specific transcription of these genes then results in localized DNA secondary structures containing unpaired bases vulnerable to mutation. Many environmental stressors can also affect supercoiling and [stress-directed mutation] directly.

But what are the mechanisms of DMs? “Mechanism” in this meaning would “refer to the circumstances affecting mutation rates” (Wright, 2000). She also defines what “random” means in neo-Darwinian parlance: “a mutation is random if it is unrelated to the metabolic function of the gene and if it occurs at a rate that is undirected by specific selective conditions of the environment.” Thus, the existence of DMs would then refute this tenet of neo-Darwinism. Two of the mechanisms of such DMs are transcriptional activation and supercoiling. Transcriptional activation (TA) can cause changes to single-stranded DNA (ssDNA) and also supercoiling (the addition of more coils onto DNA). TA can be caused by either derepression (which is a mechanism which occurs due to the absence of some molecule) or induction (the activation of an inactive gene which then becomes transcribed). Thus, knowing this, “genetic derepression may be the only mechanism by which particular environmental conditions of stress target specific regions of the genome for higher mutation rates (hypermutation)” (Wright, 2000). Such responses rely on a quick response, and this is due to the plastic phenotypes of the organism which then allow such DMs to occur. It then follows that stress-induced changes would allow organisms to survive in new environments, without a need for neo-Darwinian “mechanisms”—mainly natural selection. Thus, the biochemical mechanism for such mutations is transcriptional activation. Such stress-directed mutation could be seen as “quasi-Lamarckian” (Koonin and Wolf, 2009).

In nature, nutritional stress and associated genetic derepression must be rampant. If mutation rates can be altered by the many variables controlling specific, stress-induced transcription, one might reasonably argue that many mutations are to some extent directed as a result of the unique metabolism of every organism responding to the challenges of its environment. (Wright, 2000)

This is noted wonderfully by Jablonka and Lamb (2014: 92) in Evolution in Four Dimensions:

No longer can we think about mutation solely in terms of random failures in DNA maintenance and repair. We now know that stress conditions can affect the operation of the 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 where DNA is altered.

Jablonka and Lamb present solid evidence that mutations are semi-directed. Such mutations, as we have seen, are able to be induced by the environment in response to stress, which is due to our plastic, homeodynamic physiology. They discuss “four dimensions” of evolution which are DNA, epigenetic, behavioral and cultural. Their works (including their Epigenetic Inheritance and Evolution: The Lamarckian Dimension; see Jablonka and Lamb, 2015) provide solid evidence and arguments against the neo-Darwinian view of evolution. The fact of the matter is, there are multiple inheritance systems over and above DNA, which then contribute to nonrandom, directed mutations. The fact of the matter is, Lamarckism wasn’t wrong and Jablonka and Lamb have strongly argued for that conclusion. Epigenetics clearly influences evolution, and this therefore vindicates Lamarckism. Epigenetic variation can be inherited too (Jablonka and Lamb, 1989). Since phenotypic plasticity is relevant in how organisms adapt to their environment, then epigenetic mechanisms contribute to evolution (Ashe, Colot, and Oldroyd, 2021). Such changes that arise due to epigenetic mechanisms can indeed influence mutation (Meyer, 2015), and I would say—more directly—that certain epigenetic mechanisms play a part in how an adaptive, directed mutation would arise during the development of an organism. Stochastic epigenetic variation can indeed become adaptive (Feinberg and Irizarry, 2010).

Non-random mutations have been known to be pretty ubiquitous (Tsunoyama, Bellgard, and Gojobori, 2001). This has even been shown in the plant Arabidopis (Monroe et al, 2022), which shows that basically, mutations are not random (Domingues, 2023). A similar concept to DMs is blind stochasticity. Noble and Noble (2017, 2018; cf Noble, 2017) have shown that organisms harness stochastic processes in order to adapt to the environment—to harness function. A stochastic process is a state of a system that cannot be predicted even knowing the current state of said system.

Even all the way back in 1979, such changes were beginning to be noticed by evolutionists, such as Ho and Saunders (1979) who write that variations in the phenotype

are produced by interactions between the organism and the environment during development. We propose, therefore, that the intrinsic dynamical structure of the epigenetic system itself, in its interaction with the environment, is the source of non-random variations which direct evolutionary change, and that a proper study of evolution consists in the working out of the dynamics of the epigenetic system and its response to environmental stimuli as well as the mechanisms whereby novel developmental responses are canalized.

The organism participates in its own evolution (as considerations from niche construction show), and “evolutionary novelties” can and do arise nonrandomly (Ho, 2010). This is completely at-odds with the neo-Darwinian paradigm. Indeed, the creators of the Modern Synthesis ignored developmental and epigenetic issues when it came to formulating their theory. Fortunately, in the new millennium, we have come to understand and appreciate how development and evolution occur and how dynamic the physiological system itself truly is.

There have been critical takes on the concept of DM (Lenski and Mittler, 2003; Charlesworth, Barton, and Charlesworth, 2017; see Noble and Shapiro, 2021 for critique), like for example Futuyama (2017) who claims that DM is “groundless.” However, James Shapiro’s (1992; 2013, 2014) concept of natural genetic engineering states that cells can restructure their genomes so this “means viewing genetic change as a coordinated cell biological process, the reorganization of discrete genomic modules, resulting in the formation of new DNA structures” (Shapiro, 1993). DNA is harnessed by and for the physiological system to carry out certain tasks. Since development is self-organizing and dynamic (Smith and Thelen, 2003; Saetzler, Sonnenschein, and Soto, 2012) and since development is spurred on by physiological processes, along with the fact that physiology is sensitive to the goings-on of the environment that the developing organism finds itself in, then it follows that mutations can and would arise due to need, which would refute claims from neo-Darwinians who claim that mutations arise due to chance and not need.

Conclusion

It is clear that mutations can be (1) adaptive and (2) environmentally-induced. Such adaptive mutations, clearly, arise due to need and not chance. If they arise due to need and not chance, then they are directed and adaptive. They are directed by the plastic physiology of the organism which constructs the phenotype in a dialectical manner, using genes as its passive products, not active causes. This is because biological causation is multi-leveled, not one-way (Noble, 2012). There is also the fact of the matter that “genetic change is far from random and often not gradual” (Noble, 2013).

As can be seen in this discussion, adaptive, directed mutations are a fact of life, and so, one more domino of neo-Darwinism has fallen. Berkley claims that “The genetic variation that occurs in a population because of mutation is random“; “mutations are random“, but as we’ve seen here, this is not the case. Through the biological process of physiology and its relationship to the ebbs and flows of the environment, the organism’s phenotype that is being constructed by the self-organizing system can respond to changes in the cellular and overall environment and thusly direct changes in the phenotype and genes which would then enhance survival due to the environmental insult.

Lamarckism has been vindicated over the past 25 or so years, and it’s due to a better understanding of epigenetic processes in evolution and in the developing organism. Since what Lamarck is known for is the claim that the environment can affect the phenotype in a heritable manner, and since we now know that DNA is not the only thing inherited but epigenetically-modified DNA sequences are too, it follows that Lamarck was right. What we need to understand development and evolution is the Extended Evolutionary Synthesis, which does make novel predictions and predictions that the neo-Darwinian paradigm doesn’t (Laland et al, 2015).

Such directed changes in the genome which are caused by the physiological system due to the plastic nature of organismal construction refute a main premise of the neo-Darwinian paradigm. This is the alternative to neo-Darwinian natural selection, as Fodor noted in his attack on neo-Darwinism:

The alternative possibility to Darwin’s is that the direction of phenotypic change is very largely determined by endogenous variables. The current literature suggests that alterations in the timing of genetically controlled developmental processes is often the endogenous variable of choice; hence the ‘devo’ in ‘evo-devo’.

Darwin got quite a bit wrong, and it’s of no fault of his own. But those who claim that Darwin discovered mechanisms or articulated the random process of mutations quite obviously need to update their thoughts in the new millennium on the basis of new information informed by systems biologists and epigeneticists. The process of the construction of organisms is dynamic and self-organizing, and this is how phenotypic traits become fixed in populations of organisms. Plasticity is in fact a major driver of evolution along with the concept of genetic assimilation, which results in the canalization of the plastic trait which then eliminates the plastic response from the environment (Sommer, 2020). Phenotypic plasticity can have adaptive traits arise, but natural selection can’t be the mechanism of evolution due to Fodor’s considerations. Development can lead to evolution, not only evolution leading to development (West-Eberhard, 2003). In fact, development in many cases precedes evolution.