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Epigenetics—Sins of the Father

By Fazale Rana - June 1, 2011
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I was in Chicago recently delivering a series of lectures on my new book, Creating Life in the Lab. Before heading home, I took a quick detour on my way to the airport to find the perfect Chicago hot dog. And thanks to my hosts, I was successful.

I am not sure why I am so fond of hot dogs. Maybe I inherited my predilection. New research by scientists from the US and Israel indicates this may well be the case. These investigators have discovered that the metabolic profile of mice is influenced by the diets of their fathers and grandfathers.1 And other research suggests the results of the mice study applies to humans. Such work not only conveys biomedical importance, it also may provide a biological basis for passages like Exodus 20:5.

Biologists now recognize that inheritance involves not only the transmission of genetic information (in the form of DNA sequences) from one generation to the next, but also the transmission of chemical modifications to the DNA (called epigenetic programming.)2

These modifications impact gene expression. (Gene expression refers to the overall genetic activity of the cells comprising a specific tissue, organ, etc. Gene expression can be thought of as an inventory of the genes that are “turned on”—directing the production of proteins—and the genes that are “turned off.” Gene expression also describes the quantity of different proteins produced as a result of genetic activity.)
Environmental factors can alter the epigenetic modifications to DNA and, hence, influence gene expression patterns. And it turns out these DNA modifications can be inherited, impacting the gene expression of the offspring. In other words, epigenetic modification of the DNA caused by environmental factors experienced by their parents can provide offspring with information about the environment (like a historical DNA marker of environmental changes) at the time of their birth.

Researchers recently demonstrated that, when compared to mice fed a normal diet, mice fed a low-protein diet sired offspring that displayed elevated expression of genes in the liver involved in the production of fats and cholesterol and decreased levels of compounds called cholesterol esters. Researchers also detected chemical modifications to the region of the mice genome that regulates fat metabolism to account for the altered gene expression.

The ability to genetically transmit diet-induced changes in gene expression is advantageous for the offspring. The observed metabolic changes lead to a hoarding of calories. If the parents go hungry, then it is important for the offspring to stockpile calories. Presumably, they will be born into an environment with limited food supplies.

This result supports epidemiological studies in humans that reveal an increase in obesity and cardiovascular disease for people whose grandparents experienced famine.

This is not the first time researchers have observed the inheritance of environmentally induced changes in gene expression. (Go here to read an article I wrote about the epigenetic transmission of behaviorally induced changes in gene expression in mice.) It appears the experiences and actions of parents produce biological consequences caused by epigenetic modifications to their DNA. And these changes, and the consequences of their experiences and decisions, can be passed on to their offspring. Children are not “clean slates,” genetically speaking, but instead benefit or suffer from what their parents, and even grandparents, went through.

Could these provocative implications provide a biological explanation for passages like Exodus 20:5? Epigenetic patterning may well be the means by which God punishes several generations of children for the sins of their fathers and blesses thousands of generations of children for parental faithfulness.3

The good news is that even if epigenetic modifications are transmitted to offspring, they are reversible.
The reversibility of epigenetic patterning could also provide the biological rationale for passages like Ezekiel 18:14–17:

But suppose this son has a son who sees all the sins his father commits, and though he sees them, he does not do such things: He does not eat at the mountain shrines or look to the idols of Israel. He does not defile his neighbor’s wife. He does not oppress anyone or require a pledge for a loan. He does not commit robbery but gives his food to the hungry and provides clothing for the naked. He withholds his hand from mistreating the poor and takes no interest or profit from them. He keeps my laws and follows my decrees. He will not die for his father’s sin; he will surely live.
Endnotes
  1. Benjamin R. Carone et al., “Paternally Induced Transgenerational Environmental Reprogramming of Metabolic Gene Expression in Mammals,” Cell 143 (2010): 1084–96.
  2. Eva Jablonka and Gal Raz, “Transgenerational Epigenetic Inheritance: Prevalence, Mechanisms, and Implications for the Study of Heredity and Evolution,” Quarterly Review of Biology 84 (2009): 131–76.
  3. I realize this proposal is controversial and raises a number of questions. Go here to read my response to some of these questions.

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