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Monday, January 23, 2012

Drones, queens and genes

We inherit our genetic code from our parents and from cradle to grave that genetic sequence is immutable. We all know that forensic medicine can take any part of the human body, however small, and sequence the DNA, thus obtaining our absolutely unique genetic code. If every part of the human body contains the full sequence of DNA inherited from our parents, then why is your ear not your nose? What makes the different parts of our body different from one another is that the inherited sequence of DNA is “tweaked” so that genes that are not needed are turned down or off and those that are needed are turned up. Effectively, nature gave us a genetic dimmer switch which cannot change the sequence of genes but which can change the extent to which individual genes are expressed. By far the most striking example is the queen bee. All bee larvae contain the exact same genetic code obtained from the queen and thus they are clones. When a queen passes her sell by date so to speak, the worker bees prepare a new queen. From the thousand of cloned larvae, they select one and the wrap that larva up in a secretion from their throat region. That secretion is Royal Jelly and it contains a very unique balance of nutrients. Most importantly, it contains a protein known as Royal Lactin[1]. The effect of this is that the larva treated to Royal Jelly emerges as a queen bee, which, while sharing the exact same genetic code as the worker bee, is physiologically vastly different. Indeed up to one third of all the genes that are associated with the bee brain are differentially expressed (up or down regulated) in the queen bee. Queen bees live for years while worker bees live for only weeks. The queen bee will uniquely produce 2,000 eggs on a summer’s day while worker bees are sterile. This modification of gene expression is called epigenetics and it is of enormous importance in human nutrition.

During  life in our mother’s womb, nature’s genetic dimmer switch gets to work. Without changing a single aspect of genetic sequence, it switches up some genes and switches down others. It does so to make sure that the new born baby has its genetic profile made to measure for the external environment into which it enters at birth. There are two ways to look at this phenomenon, the first of which is physical. John Hammond, a famous UK animal scientist reported in 1938 on a study, which crossed the very large Shire horse with the very small Shetland horse. When a Shire stallion mated a Shetland mare, the offspring had the physical proportions of the Shetland mare. Vice versa, when the Shetland stallion mated a Shire mare (with help I assume!), the offspring had the proportions of the Shire mare. Even though all of the foals born had 50% Shire and 50% Shetland genes, their life in the womb determined their birth size. The size of the uterus in gestation over-rode the genetic inheritance. This was among the first studies to show that our inherited genetic sequence is subject to significant up- and down-regulation during pregnancy. The second factor that emerged as a major determinant of pregnancy modulation of gene expression was diet. It began with historical studies that linked birth weight and length to the risk of many diseases in adulthood. Thus for example, in adulthood, the risk of developing high blood pressure was shown to rise dramatically among those who had a lower than average birth weight and a higher than average placental weight.  When this data began to emerge in the early 1980’s it was regarded as almost heretical by nutritional epidemiologists for whom all chronic disease could be explained by poor eating habits. In time, the evidence grew and animal experiments bore out the theory. Today, we absolutely accept optimal nutrition in pregnancy is essential to minimize disease later in life.

Pregnancy is not the only period where nutritional factors can cause the expression of our genes to change with life long effects. The second vulnerable period is the first 2 years of life. (This period, combined with the duration of pregnancy,  is referred to these days as “The first 1000 days”). During the first 2 years of life, diet can play a role in permanently altering both our physique and our cognitive function. If growth is impaired during this period in any sustained manner, then the person will be permanently stunted, that is too small for their age. Stunting is widespread in developing countries. During the first 2 years of life, our brains grow both in size and in complexity. In adults, the brain consumes about a quarter of all calories consumed. In infants, this figure rises to nearly three quarters of calories consumed. If children are inadequately nourished during this period, their cognitive function is permanently reduced.

To understand why nature has given us this gene dimmer switch we need to consider its evolutionary advantages. In pregnancy, the biological profile of the mother, in which diet plays a powerful role, lays down a permanent imprint on gene expression. If times are frugal, the birth weight falls and the baby is programmed for a frugal existence. If that child grows to be an adult in a very non-frugal and obesogenic environment, then they cope poorly such that chronic disease rates rise. Thus we adapt to the biological environment prevailing during pregnancy in the expectation that that will prevail. In times gone by, that adaptive mechanism had a great evolutionary advantage. As regards the evolutionary advantage brain development in the first 2 years of life, that lies in the ability to absorb the culture into which the child is born. Chinese babies learn to speak Chinese and to absorb Chinese culture. Each culture needs that time to imprint all of its values into the new born. The brain of a foal is hard wired at birth such that instantly, the foal stands and runs with the herd. No schooling is needed.  Horses just haven’t evolved as man has with its “plastic” infant brain.

When the human genetic code was sequenced, the “genohype” predicted great medical miracles. We now know that sequence is one thing but how that sequence is expressed is what makes a huge difference and we know that a balanced optimal diet will lead to the optimal changes I gene expression. We now also know that one of the main public health nutrition challenges is maternal nutrition. It is a challenge that the high priests of healthy eating are unhappy with because it distracts them from their prevailing wisdom with which they are very happy.


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