Saturday, November 3, 2012

52. Epigenetics

When Darwin published his theory of biological evolution, the field of genetics had not yet taken shape. Naturally, Lamarck, whose work on evolution preceded that of Darwin, was also unaware of the crucial role genetic mechanisms play in the evolution of species. We now have the familiar concepts of 'genotype' and 'phenotype'. The term genotype refers to the genetic blueprint encoded in the DNA chains. Phenotype, on the other hand, signifies the characteristics manifested by an organism; it is the structure created by the organism from the instructions in its genotype.
In phase-space language, genotypes correspond to the search space, and phenotypes to the solution space.

Biological evolution is generally believed to be Darwinian, or rather neo-Darwinian. Lamarck’s evolution model, or Lamarckism, on the other hand, was based on two premises: the principle of use and disuse; and the principle of inheritance of acquired characteristics (without involving the genotype).

The Lamarckian viewpoint is not acceptable because it runs counter to the central dogma of molecular biology (cf. Part 43). The field of research called epigenetics has brought us close to Lamarckism in a superficial sort of way, but without violating the central dogma of molecular biology. It is now clear that changes other than those in the sequence of nucleotides in DNA, acquired during the lifetime of parents or grand-parents, can sometimes be inherited in the next few generations. Gene expression or interpretation (cf. Part 48) can be influenced by molecules hitchhiking on gametes (germ cells) and therefore on genes. This temporarily heritable hitchhiking of the genes is called epigenetic inheritance.

Genes are portions of the long sequence of nucleic acids in the DNA chain, and contain coded information for synthesizing the various proteins. And we have known since the days of Mendel that not all genes are active all the time. Some genes are dominant, while others are recessive. One of the Mendelian laws of genetics is that it is the combination of dominant (or switched on) and recessive (or switched off) genes, inherited from the parents, that dictates the characteristics (phenotype) of an offspring. We saw in Part 48 how the presence of certain chemicals can influence gene expression, and once a gene has been switched on, it acts as a switch which can alter the ‘on’ or ‘off’ states of other genes. Hormones are one example of what can influence gene activity.

Can chemicals other than hormones, for example those in the diet of an organism, also influence gene expression? The answer is 'Yes'. And not just food, but even the mental state of an creature can be responsible for the secretion of chemicals which can influence gene expression.

But from the point of view of genetics and transmittal of acquired characteristics, the influence on the transmittal mechanism of genes should be of an irreversible, perpetual nature; only then can it affect the future generations in a permanent manner; then only can we have an inheritance of acquired characteristics by the progeny. This is not found to be the case. Epigenetic transmission of acquired characteristics does not last for a significantly large number of generations.

Epigenetic effects influence the phenotype over a few generations, without changing the sequence of nucleotides along the DNA chain.

One particular heritable marking of DNA that has been investigated substantially is that of methylation, i.e. attachment of the -CH3 group to one or more nucleotides along the DNA chain.

It has been found, for example, that methylation is quite frequent in cancer cells.

Methylation affects gene expression and, as a feedforward mechanism, can have serious transgenerational effects. Epigenetic changes can be passed through the germ line for a few generations. And epigenetic changes can occur throughout the life time of an individual: Methylation/demethylation can turn some genes off/on.

Richard Dawkins' phrase 'The Selfish Gene' sums up the essence of neo-Darwinistic evolution; at least the Dawkins version of it: Natural selection acts only on genes, via their expression in an organism's body and behaviour. The genes are not naked. The phenotype is the vehicle that promotes their interest of propagating to the next generation. The organism is the survival machine for the genes. Dawkins spoke of the 'selfish gene' because the gene promotes its own survival, without necessarily promoting the survival of the organism, group or even species.

There are two aspects of a gene. The specific sequence of the four nucleic-acid bases (A, T, G, C) along the backbone of DNA; and the paraphernalia of interactions that occur on the peripheral surface of the long DNA molecule. The backbone part does not change, except through the occasional mutation, or during 'chromosomal crossover'. Epigenetics is all about what happens on the surface, with no influence on the backbone sequence of the nucleotides.

Genes propagate over many generations with a high degree of integrity because the replication process involves the strongly bonded backbone structure of DNA. By contrast, the epigenetic alterations are of a temporary (few-generations) nature; there is no evidence that the changes are permanent. In view of this, Dawkins has responded to the claims of epigenetics by replacing his phrase 'selfish gene' by 'selfish replicator':

"The 'transgenerational' effects now being described are mildly interesting, but they cast no doubt whatsoever on the theory of the selfish gene". . ."Whether [epigenetic marks] will eventually be deemed to qualify as 'selfish replicators' will depend upon whether they are genuinely high-fidelity replicators with the capacity to go on forever. This is important because otherwise there will be no interesting differences between those that are successful in natural selection and those that are not."

Dawkins points out that if the epigenetic effects fade out within the first few generations, they cannot be said to be positively selected.