Epigenetics: Sins of the fathers?

A picture worth a thousand words?

The term, ‘Central Dogma Theory’ was coined soon after the structure of DNA was elucidated back in 1953. In essence, it refers to the flow of genetic information. Thus, as stated by the theory, genetic information flows in one direction: from gene to intermediary RNA molecules, finally culminating in the production of proteins, the building blocks and rate controlling molecules of life. It was anathema to consider information flowing the other way. And the main heresy, in particular, involved the consequence of environmental factors influencing gene expression with heritable consequences. Sane, grown-up biologists would shudder at the very thought. To think so invited the resurrection of Lamarckism, an 18th-century proto-evolutionary theory. This theory, as presented by the French savant, Jean-Baptiste Lamarck, postulated that the environment could influence the genetic form of an organism and hence propagate for posterity. The classic example involved the giraffe. Lamarck’s hypothesis contends that in lean times giraffes would stretch their necks to obtain succulent leaves further up the tree branch. In time the neck would be elongated and this increase in length would be passed on to their offspring. Over generations, an elongated neck would become fixed in the giraffe population. The idea has a certain elegant simplicity especially as it was formulated well before the genetic mechanism had been discovered. However, subsequent experimentation, often involving cutting the tales off mice, showed that Lamarckism was not a viable mechanism for the transmission of genetic information. 

Conventional genetics contends that gene expression can be altered through dynamic mutation. Alteration of the structure of DNA can occur through mutagenic insults from natural radiation, replication errors and chemicals within the cell environment. If this change occurs within the ‘germ cells’, cells responsible for the production of sperm and eggs, this change may be passed on to subsequent offspring and a given mutation may result in the loss of gene function. This underlying mechanism is important for the transmission of genetic disease. If a mutation occurs in cells, other than the gonads (somatic cells), the gene alteration, in certain differentiated cells and in certain genes (oncogenes), may result, or contribute to the initiation of cancer. This model seemed to be all-encompassing with regard to gene expression up to the middle of the last century, but things were about to change.

Let us reminisce to the last Great War. In the latter part of 1944, the Allies seemed poised to liberate the Netherlands and storm into the Third Reich. However, for reasons outside the remit of this post, there was a winter’s pause. The unliberated Dutch folk experienced a period of intense famine during late 1944 and early 1945. Postwar clinical trials exposed an interesting medical trend. Children born to pregnant mothers during this critical 1944/1945 period exhibited relatively high rates of obesity and heart disease in comparison to a control population. Thus, the shade of Lamarckism seemed to emerge from a deep pit of despond, shake off its anachronistic shackles to insinuate on a stunned biological community (Flaxen waxing bollox). Was it conceivable that environmental factors could influence gene expression? Further experimentation and medical trials confirmed the apostasy.

It became quickly established that the initiating event was not due to classical genetic mutation altering the genetic code. Gene expression seemed to be altered by other means not involving a change to DNA base pairs. To cut a long story short, with regard to the Dutch study, it was discovered that a methylation change occurred at a growth factor gene called insulin-like growth factor II (IGF2). The methylation status of a gene controls its expression. In this instance, the IGF2 gene was upregulated. I’m not going to delve into the convoluted biochemistry. My blog with regard to biology is pitched at the intelligent layman/laywomen. For those who would like to know more concerning the fascinating world of genetics, I suggest a Google search. We truly live in wondrous times with information, often erroneous information, a mere click away. Changes in DNA chemistry and DNA conformation resulting in changes in gene expression, influenced by the environment, comes under the auspices of epigenetics. Epigenetic changes can occur in the womb and therefore the mother’s health status appears to be important for subsequent offspring. That said, post birth lifestyle choices may also have an influence on our genetic makeup and heritage.  

What I find fascinating is how the bodily environment can influence genes resulting in the modification of gene expression. I mentioned methylation as an important mechanism in turning genes on and off. The addition of methyl groups to a gene generally prevents the expression of that gene, while the removal of methyl groups promotes expression. Other mechanisms involve a change in the conformational status of the DNA and associated protein complex (histone modification). How change is conveyed at the cellular level is poorly understood at present and much research is being devoted to uncovering the underlying biochemistry. 
Clearly, epigenetic changes are highly important in contributing to our genetic makeup. Individual lifestyle influences (voluntary and involuntary) are only part of the story. The epigenetic status of our parents and grandparents will have a role to play in our genetic milieu. Surely the sins of the fathers will project unto their offspring to the nth generation. Predictably, commercial companies will latch onto the ‘epigenetic phenomenon’. A potion for all our ills will come under the guise of ‘genetic science’. Beware, of the new snake oil. For there is little doubt that companies will take commercial advantage and promote ‘gene modifying’ products supported by baseless pseudoscience. You have been warned.