The Epigenetic Model

Let us start by trying to provide a basic description of an epigenetic model that defines a mechanism that can regulate gene activity in a way that may be independent of the DNA sequence. This ‘independence’ is based on the idea that epigenetic mechanisms are able to switch on/off specific gene-alleles in response to different ‘environmental’ stimulus, which may originate outside the cell nucleus. The following diagram attempts to illustrate this process as follows:

However, by way of further background context for this discussion, evolutionists holding to the paradigm of modern evolutionary synthesis, sometimes known as neo-Darwinism, often consider the idea of natural selection, and random genetic mutation, to be the primary mechanisms driving evolution. As such, those of the neo-Darwinism school of evolution have tended to resist and/or reject many of the ideas being forwarded by epigenetic research. For, in the context of neo-Darwinism, evolution is a slow process of gene mixing and random mutation change within the genome, which it is assumed would only cause small phenotype changes within any given generational timeframe. So based on the idea of natural selection, and Mendelian inheritance, the gene has been seen as the primary, if only mechanism that ‘engineers’ the evolution of cells and in-turn larger organisms. Therefore, the central idea of epigenetics in which cellular interactions with its environment, both internal and external to an organism, can then cause changes to the genome is understandably a matter of much debate.

So what role ‘might’ epigenetics have to play in the evolutionary process?

Clearly, any lay-person attempting to address this question has to proceed with caution because the technical details of the debate are invariably very complex, such that many discussions can end up being based on more anecdotal evidence than facts. However, by necessity, such evidence is often the starting point of any learning curve, which is the justification now given for two ‘hypothetical’ experiments based on genetic mechanisms that previous discussions have, at least, outlined. First, let us assume that you could take the 23 chromosomes from the nucleus of an egg cell of one woman and insert them into the nucleus of a female egg containing the another set of 23 chromosomes, such that we might appear to have the required 46 chromosomes and the XX pairing of a female zygote. Alternatively, we might take 23 chromosomes from the nucleus of a sperm cell from two different males and insert both sets of 23 chromosomes into the empty nucleus of a female egg, such that we might appear to have the YY combination of an ambiguous zygote having no X chromosome.

Would either be a viable combination?

Current, albeit somewhat anecdotal, evidence suggests that both combinations outlined would fail to produce a healthy zygote because of genomic imprinting, which is described as a epigenetic mechanism by which genes within the DNA sequence is marked to indicate whether the chromosome came from a male or female. While we might immediately recognise the anomalous nature of a YY-zygote only having DNA from two males, the XX-zygote combination would also be recognised as anomalous as the second X chromosome would be flagged as originating from a female rather than a male. So while natural selection would prevent either case by the normal requirements of sexual reproduction, these somewhat hypothetical examples highlight the possibility of additional mechanisms at work, although the exact role of epigenetics in evolution may not yet be empirically proven.

But why start with a hypothetical example?

While it is not entirely clear whether genetic research is yet capable of such experiments, ignoring all ethical constraints, probability would suggest that it may only be a matter of time given the current rate of progress. If so, and following on from the last discussion that touch on the future direction of human evolution, genetic and epigenetic inheritance mechanisms may be subject to man-made manipulation sooner than most people may realise. Therefore, the issue of epigenetic inheritance may possibly be an important facet of further human evolution, especially in the near-term, if human society continues to change the global environment and not necessarily in a good way, e.g. climate change, urbanisation and pollution.

So what is the  evidence for epigenetic inheritance?

The original accepted wisdom was the epigenome, i.e. the DNA genome plus epigenetic tags, is completely erased within the early stages of zygote development, although the previous example suggest that these flags remain in place within the gamete cells, i.e. sperm and egg. However, there is now growing evidence that some epigenetic tags may survive or possibly bypass this stage and therefore be passed to the next generation in a process called transgenerational epigenetic inheritance. However, this position is still much debated because it is often unclear whether the change is due to random mutations of the DNA or some effect that is passed through multiple generations, e.g. F1, F2 and F3. As pointed out earlier, the eggs of an F3 generation exist in the foetus of a F2 generation, while still in the womb of her F1 grandmother. Therefore, environmental condition, e.g. diet, toxins, hormones, might well affect all three generations, although conventional wisdom might still suggest that most of the epigenetic tags of the grandmother (F1) would be lost as the (F2) zygote-foetus developed and only exists in the eggs gametes of some potential F3 generation. Therefore, for epigenetic inheritance to be considered as an enduring change, it is argued that sustained phenotype change has to be observed in the (F4) generation. On this basis, any epigenetic change may be transitory in nature and may well be reversed, if the environmental conditions change again, especially over the time period implied by four human generations, e.g. 80 years. As such, a degree of caution may well be necessary before simply accepting all speculative commentary on the subject of epigenetic inheritance, although this cautionary note does not mean the idea should simply be rejected. However, as an initial generalisation, we might still assume that ‘wholesale change’ of the human genome and its phenotype variance only takes place at a relatively slow pace through the accepted processes of natural selection, gene mixing and random mutation.

But what potential epigenetic effects can still alter gene expressions within a single generation?

Transgenerational epigenetic inheritance is described in terms of the information passed from one generation to the next that may caused phenotype changes without necessarily causing changes to the DNA structure. Within this definition, there are four basic mechanisms being investigated:

  • Self-sustaining metabolic loops: where protein products of a gene in-turn affect the transcription of other genes.

  • Structural templating: where the structure of proteins is changed to match the parent.

  • Chromatin marks: where methyl or acetyl groups bind to DNA nucleotides or histones causing change in gene expression.

  • RNA silencing: where small RNA strands interfere with the transcription of DNA.

Anecdotally, humanity has long recognized that traits of the parents can often be seen in offspring, hence the long history of selective breeding of plants and animals. However, the practice of selective breeding does not really explain how these traits were passed on, such that the nature versus nurture debate has continued in the present form of genetics versus epigenetics. Based on previous discussions, it has been shown that the human DNA sequence is encoded into 46 chromosomes, i.e. 22 pairs + X/Y, which we might initially assume explains all possible permutations of gene expression occurring within the cell nucleus. This said, it now appears to be accepted that epigenetic tags do provide a mechanism by which specific genes can be switched on and off. While this appears to be a very logical mechanism, it is not clear that it provides an overall causal explanation, i.e. what determines which genes should be switched on/off in the estimated 37 trillion cells in the human body. By way of a possibly very poor analogy, if we compare the total DNA sequence in a cell to all the recipes in a cookery book, the eventual function of a specific cell would only be analogous to just one recipe, which then leads us to a key question:

Who, or more accurately what, decides which specific recipe applies in each of our 37 trillion cells?

For most complex organisms are a construct of many different kinds of cells, which are specialized to perform different functions. For example, a human liver cell has a very different biochemistry, i.e. recipe, to that of a nerve cell, even though each cell has the same DNA instruction set, i.e. the entire cookery book. While it might be simply assumed that any specific biochemical function is controlled by equally specific enzymes-proteins, different sets of genes have to be turned on/off in order for these enzymes-proteins to exist. Therefore, the idea that simply labelling this process with a name, i.e. ‘cell differentiation, provides any adequate causal explanation might be challenged. Even so, it is clear that the processes implied by ‘cell differentiation’ can change the function of a cell in terms its size, shape, metabolic activity and membrane sensitivity to other chemical signals. Typically, these changes are explained in terms of ‘gene expression’ caused by ‘epigenetic mechanisms’ that are usually assumed to be reset in foetal development of the zygote and rarely involve any change to the DNA sequence. So, within this chicken-and-egg debate, the epigenetic tags would have to be created by specific genes within the cell in response to environmental conditions confined within the zygote-to-foetus process.

But where does the ‘master blueprint’ of the final adult form exist within this process?

Let us reiterate that humans, like all mammals, are a construct of two basic types of cells, i.e. somatic and germinal. We might realise that the germinal-sex cells of reproduction only play a small part in the 37 trillion cells making up the structural-phenotype form of humanity. However, this description ignores the very key role played by another type of cell:

Stem Cells: These are undifferentiated cells, which eventually differentiate into specialized cells. However, they initially divide, via mitosis, to produce other stem cells. In mammals, stem cells are sub-divided into adult and embryonic stem cells. In adult form, stem cells might be described as a repair system within the body, which can replace some, but not all, adult somatic cells if damaged. However, in a developing foetus, stem cells differentiate into a very wide range of specialized cells, both mind and body.

So to conclude, it might be stated that the human foetal development starts when a haploid sperm-gamete cell fertilizes a haploid egg-gamete cell to creates a single diploid cell, i.e. 23 chromosomes from each parent combine to form a zygote. In the first few hours after fertilization, the first zygote cell divides into identical cells, but eventually these cells begin to specialize and start to form a hollow sphere of cells called a ‘ blastocyst ’. As we might now have come to expect, the blastocyst is but the start of another series of incredibly complex processes, each seemingly with their own specialised vocabulary of labels, names and jargon, which proceeds by cell division and cell specialisation. Whether we, as yet, fully understand how all these processes are orchestrated by the ‘master blueprint’ of genetics has been questioned on the grounds of the debate that still surrounds the genetic and epigenetic mechanisms at work. While entire volumes have already been written of the minutiae of many aspects of this biological evolution, which this discussion has only outlined, it would seem reasonable to assume that even more volumes have yet to be written. However, even at this stage, the advocates of man-made change should possibly be humbled when reviewing the achievements of billions of years of evolution and the resulting complexity, which we may have only  started to comprehend.