Barry Lester taught us about epigenetics. He started with reviewing the background of “fetal origins” and the concept of “fetal programming”. Can the study of genes and environment at the cellular level inform us about molecular influences on behavior? The hypothesis states that susceptibility in cardiovascular disease, non-insulin-dependent diabetes mellitus, and the insulin resistancy syndrome, is programmed in utero as a response to fetal malnutrition. This dates to the German starving of Dutch mothers during World War II. There was a relationship between low birth weight and hypertension, 40 years later. The general concept is that reduced fetal growth leads to altered structure and function in the fetus, leading to increased risk for adult disease. During the famine, the fetuses were starving and they wanted to prepare themselves to survive in a famine environment. Instead, the famine ended and the babies were born into adequately nourishing environments. They had adapted their systems to slowed-down metabolism and couldn’t adapt.
Developmental plasticity enables the organism to change, reprogram structure and function in response to environmental cues. The adaptive significance is that plasticity enables a range of phenotypes. Many studies have replicated this finding. The idea is that your risk of disease depends on the extent to which you are prepared for, or match with, the external environment. Can these effects be produced by environmental insults other than malnutrition? What might be the underlying mechanisms? Could epigenetics provide the molecular basis for fetal programming? What might be the applicability of this model beyond chronic disease to behavior?
There is evidence that the fetal origins theory relates to the etiology of neurobehavioral problems and mental illness. Low birth weight is related to schizophrenia, depression, and psychological distress. What is the molecular basis?
Epigenetics has to do with the heritable and stable control of gene expression beyond DNA sequence. It is heritable – can be passed on to successive cells – yet does not alter the genetic sequence, and inter-generational. It is stable and cannot be altered. It is environmentally sensitive. There are critical periods (a lot of this happens in periods of rapid development) and reversible. Epigenetics controls gene expression and transcription, turning off and on the gene. The gene stays the same, but what the gene makes happen is changed. Conrad Waddington (Professor Genetics, Univ. Edinburgh, 1905-1975) described epigenetics as “cross talk” between the gene and the environment.
Epigenetic changes happen all the time. The field started in cancer. Epigenetic research has since expanded into behavior. Barry’s “favorite example” is that in which the mother is a drug addict and is loaded with addiction genes. If you could turn them off, the baby will inherit the same DNA but will not inherit the addiction. This is pure fantasy but possible. Epigenetics refers to the changes in gene activity, expression, without changing the gene. It can be silenced, enhanced, and change can be transferred to the next generation some of these changes can be reversed.
The most common mechanism in which environmental influences can produce stable alterations is DNA methylation. (Histone is another one. The outer layer of the package of DNA is histone.) The metaphor is gum on a light switch. Epigenetic changes occur when genes are being replicated. The DNA is transcribing to RNA and that is producing proteins. The amino acids guanine and cytosine hang out at the gene transcription sites – CPG islands. A protein puts little methyl tags on the gene. That is like gum on a light switch; it turns off the gene.