Artist’s impression of chromatin commissioned by Geneviève Almouzni. Base pairs (yellow) couple along DNA backbone (pink), which in turn coils intimately around histone proteins (blue and white) to form chromosomes (red) in the nucleus.
Artwork by Nicolas Bouvier

Brona McVittie reports :: June 2006

Over 50 years have passed since Watson and Crick first published the three-dimensional structure of the DNA double helix. With Darwinian evolutionary theory now so widespread, the discovery that DNA encodes hereditary characteristics has proven popular. When Crick passed away last year, broad media coverage signified how much these concepts are accepted beyond the scientific community. However, we are coming to realise that gene-centric theories of evolution are limited in their scope. The genetic blueprint, like a complex musical score, remains lifeless without an orchestra of cells (players) and epigenotypes (instruments) to express it.

Science is now uncovering what plays our genetic score, and it appears this performance can change dramatically between generations without alteration to the DNA sequence. The field of epigenetics seeks to determine how genome function is affected by mechanisms that regulate the way genes are processed. Epigenetic factors include both spatial patterns, such as the arrangement of DNA around histone proteins (chromatin), and biochemical tagging.

There are hundreds of different kinds of cells in our bodies. Although each one derives from the same starting point, the features of a neuron are very different from those of a liver cell. With some 30 000 genes in the human genome, the importance of silence, as with any orchestral performance, must not be underestimated. As cells develop, their fate is governed by the selective use and silencing of genes. This process is subject to epigenetic factors. DNA methylation patterns play a role in all sorts of phenomena where genes are switched on or off, from the splash of purple on a petunia petal to the growth of cancerous tumours.

Failure to silence genes can produce a hazardous cacophony. Too little DNA methylation can alter the arrangement of chromatin. This, in turn, affects which genes are silenced after cell division. Too much methylation can squash the work done by protective tumour suppressor and DNA repair genes. Such epimutations have been observed in a wide range of cancers. These epigenetic insights are offering new therapeutic avenues for exploration.

Epigenetics also provides a means by which genetic material can respond to changing environmental conditions. Although plants do not have a nervous system or brain, their cells have the ability to memorise seasonal changes. In some biennial species, this ability is linked to their capacity to flower in the spring, when warmer ambient temperatures are detected. Research has shown how exposure to cold during winter triggers structural changes in chromatin that silence the flowering genes in some kinds of cress. These genes are reactivated in spring when the longer days and warmth are more conducive to reproduction.

The environment can also prompt epigenetic changes that affect future generations. Recent laboratory studies on inbred mice demonstrated how changes to their diet might influence their offspring. Their fur can be brown, yellow or mottled depending on how the agouti gene is methylated during embryonic growth. When pregnant mothers were fed methyl-rich supplements such as folic acid and vitamin B12, their young developed mainly brown fur. Most of the babies born to control mice (not given the supplements) had yellow fur.

Just as the conductor of an orchestra controls the dynamics of a symphonic performance, epigenetic factors govern the interpretation of DNA within each living cell. Understanding these factors could revolutionize evolutionary and developmental biology, and thus affect practices from medicine to agriculture. To answer Watson, "The genetic alphabet is more akin to the word of God, and its translation to his hand".

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