October 3, 2016

The Developing Genome – the rise of epigenetics

A new book, The Developing Genome, describes the fascinating developments in the the field of epigenetics. These developments may require us to revise our beliefs about the influence of genes.

The prescientific way of thinking about nature

Before 1859 there was roughly only one way of thinking about nature: all species have been made by 'the creator' in such a way that they fit well within the environment in which they live. But roughly two centuries ago people began to develop serious alternative ways of thinking about nature. In 1809, Lamarck published his hypothesis which offered an explanation for why organisms fit so well in their environments. He thought that parts of the body which were used a lot would become stronger and bigger because of it. In addition to this, he thought that traits which an organism acquired during its lifetime would be passed on to its offspring.

Darwin's theory of evolution

In 1859 Charles Darwin published his theory of evolution after several decades of study. His ideas were both based on many years of observation and inspired by ideas from other fields such as geology, paleontology, and economics. Darwin had observed that individuals in a population have different heritable characteristics and also that they generally produce more offspring than the environment can support. He argued that individuals which, due to their traits, are well adapted to their environment generally produce more offspring. Due to some unknown process of inheritance this offspring would have a higher probability of also having these traits. This explains why over time traits which provide benefits within these environments increase in frequency over time. Darwin called this mechanism descent with modification by natural selection.

An overwhelming variety and amount of evidence has now supported Darwin's theory. This evidence is not only based on study of the past (for example of fossils) but also on direct observation in the here and now. An example of the latter type of evidence is the evolution of drugs resistant bacteria. Darwin showed that evolution happens but he hardly had any idea about what mechanisms underlie it. For example, he knew nothing about DNA.

The neo-Darwinistic synthesis: combination of Darwin and genetics

In the twentieth century an explosion of knowledge happened in the field of genetics. Based on the work by Georg Mendel scientists went looking for heritable factors. By 1950 it was known that chromosomes mainly consist of DNA and in 1953 Watson & Crick identified the structure of DNA: a double stranded twisted helix. The growing knowledge on genetics made it possible to get an ever clearer picture of how evolution happens. This combination of Darwin's theory of evolution and the science of genetics is called the neo-Darwinistisc synthesis. Today, it is the dominant way of thinking about evolution.

This theory said that genes form the only basis for evolution and that genetic material does not change under influence of the environment and that acquired traits cannot by passed on to offspring (which Lamarck thought was possible). Darwin did not completely reject Lamarck's ideas, neo-Darwinism does. Within this paradigm it is acknowledged that the environment exercises a certain influence on how individuals develop. This view is reflected in the so-called nature versus nurture debate (the influence from genes versus the influence from the environment). Through twin studies scientists tried to determine the relative influence of both factors on a variety of characteristics of individuals (such as intelligence).

Epigenetics

Several decades ago small cracks began to emerge in neo-Darwinism and these cracks have become bigger and bigger. They are now so big that the paradigm needs to be revised. What caused these cracks is a paradigm which is called epigenetics. This term was coined by Conrad Waddington in the 1940s. He realized that development requires genes to respond differently to different contexts.

That idea was based on the insight that cell of embryo's are pluripotent: they can develop into all the different types of cells that make up the body. In the 1960s it was already known that genes can be activated or deactivated by molecules placed on top of them. Hence the name epigenetics ('epi' means 'on top of'). Epigenetics studies how this interaction between genes and environment takes place.

The Developing Genome

The field of epigenetics is growing rapidly and much knowledge is emerging. A new book by David S. Moore, The Developing Genome, An Introduction to Behavioral Epigenetics, gives a fascinating overview of the status quo. The details of epigenetics are all about the highly complex field of molecular biology. For lack of space and knowledge, I can only lift a tiny tip of the veil of what is known. Simply put, environmental factors leave epigenetic marks (in the form of molecules) on our DNA which have a critical impact on how DNA functions and how we develop. The two most important epigenetic mechanisms are methylation and acetylation. To explain these I'll first briefly say something about DNA.

DNA is found in the chromosomes which are in the nuclei of our cells. It has two long strands which are intertwined with each other into a double helix. Genes are segments on DNA which contain information on the basis of which proteins are made. Depending on their specific characteristics these proteins fulfill many functions in our body. DNA is located in the nucleus of the cell but proteins are produced outside of the nucleus. The molecule RNA copies the required information on the DNA (this is called transcription) and transports it outside of the nucleus were the protein is made. Chromosomes do not only contain DNA but also specific proteins called histones. The long DNA molecule is wound around these histones.

Methylation and acetylation

The first epigenetic mechanism mentioned above is methylation. This means that a methyl molecule gets attached to the DNA molecule. Because of this the genetic information on that location can no longer be read and copied by RNA. Thus, methylation deactivates that specific gene. The second mechanism is acetylation which means that an acetyl molecule gets attached to histones. This causes the DNA to be less tightly wound around the histones. A tight wounding makes reading genes hard so acetylation makes it easier.

DNA methylation deactivates genes, acetylation activates them. Although not irreversible, the effect of methylation is very stable. Deactivation of certain genes in childhood can lead to long lasting or even permanent effects on development. Acetylation is less stable. Activating and deactivating genes, gene regulation, is a process which continues throughout our lives. The total of all epigenetic marks on DNA is called the epigenome. The epigenome influences our development in a far reaching and long lasting way. This influence not only concerns subtle and small characteristics but also large physical characteristics.

Epigenetic characteristics do not only influence our individual development. There are also epigenetic effects over generations. Although controversial, there is growing evidence of direct inheritance of certain epigenetic traits.

What can we do with epigenetics?

For now, the growth of the epigenetic body of knowledge is mainly of scientific interest. There are no clear practical recommendations which can be made on the basis of this knowledge. It seems wise to distrust any publications which pretend otherwise. As knowledge continues to grow, however, these practical applications will also emerge. Scientists may understand the development of diseases better and develop better treatments which directly intervene in the epigenome.

Equally important is that we may have to change our view of ourselves. Genetic determinism, the idea that our genes are a blueprint for our traits, is too simple. We aren't slaves to our biology. All our traits, both physical and psychological, develop as a result of the interaction between DNA and our environment. Our environment can get under our skin in our epigenome. What we do and in which contexts we engage ourselves will keep on influencing the way our DNA functions.

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