Monday, October 31, 2016

Evolution Evolves: Genetics, Natural Selection, and Epigenetics

Darwin’s indication of natural selection as a means of explaining the evolution of species has been successful at explaining much of what was known about life in his era.  He was apparently prescient enough to realize that there could be other mechanisms that might also play a role.  The growing recognition of epigenetics as a factor in evolution has created an extension of Darwin’s theory that has gained prominence in recent years.  Steven Rose presents a concise summary of these developments in an article in the London Review of Books with the curious title How to Get Another Thorax.

First, a definition is required.

“Phenotype is a Humpty-Dumptyish word, but can be roughly taken to mean any observable feature of a living organism, at any level from the molecular to the cellular to the entire organism and its behaviour. Richard Dawkins extended its definition by asserting that the dam a beaver builds is part of its phenotype.”

The term epigenetics in its current usage has been attributed to C. H. Waddington who coined it in the 1940s as a mechanism by which the attributes of a member of a given species might be modified by experiences during its development.  Waddington believed that these altered properties could, if reproduced over multiple generations, become incorporated as a heritable property of the species. 

“Epigenetics seeks to explain how, starting from an identical set of genes, the contingencies of development can lead to different outcomes.”

“He [Waddington] also went further, proposing that if a strongly canalised phenotypic change was repeated generation after generation, some random mutation would eventually catch up with it and it would be assimilated into the genome. He demonstrated that this was possible by exposing developing fruit fly embryos to ether, which induces them to develop a second thorax. After some twenty generations (it takes a fruit fly about seven days to develop from a fertilised egg to an adult ready to mate, so experiments using them are fast and easy), the flies developed the second thorax without exposure to the ether – the epigenetically induced bithorax had become fixed in the fly’s genome.”

Waddington was making these claims before knowledge of the structure of DNA and before modern techniques for genomic examination were available.  His ideas never caught on and faded from view for a time, only to return as research provided new insights.

The very fact that a single set of genes can produce an entire organism with many different types of cells indicates that there must be mechanisms that can turn genes on and off as needed to produce the cells with the various necessary functions.

“….the literary metaphor, universally employed by molecular biologists, isn’t accidental; they think of DNA as the language in which the Book of Life is written – in a scheduled flow during the development of the foetus, according to whether the cells are destined to become liver or brain, blood or bone. No gene works in isolation but as part of a collaboration. Many genes may be required to produce a single phenotype – more than fifty main gene variants have been shown to affect the chances that someone will contract coronary heart disease, for example – and a particular gene may influence many different phenotypic traits, depending on which organ’s cells it is active in. It is during this period of rapid growth that living organisms are at their most plastic, responding to environmental challenges by modifying anatomical, biochemical, physiological or behavioural phenotypic traits. This is epigenetic canalisation.”

The fact that environmental factors can alter genetic performance is obvious from studies of identical twins.  Beginning with the same genomes the pairs gradually drift apart in terms of health outcomes until eventually life expectancy becomes very poorly correlated.  This source provides relevant data.



“For molecular biologists, the task has been to discover the mechanisms by which external causes switch genes on and off. This has meant coming to terms with the significance of the fact that DNA is not a naked molecule but is protectively wrapped in a cling-film of proteins – histones – portions of which have to be peeled away before any particular length of DNA can be read; environmental factors affect the peeling process, and therefore the selection of genes to be read. A second important finding has been that during development segments of DNA become ‘marked’; a small molecular chunk, a methyl group (CH3), is attached to one of the DNA bases (generally C, cytosine). The presence of the methyl group prevents the DNA from being read – that is, it switches the gene off. Removing the methyl switches the gene on again. As the field of epigenetics develops, many more such mechanisms are likely to be discovered.”

“The environment in which a developing embryo is immersed is not unchanging; in mammals the hormonal status or diet of the pregnant female will affect the embryo and foetus, which responds adaptively to environmental challenges as methyl groups are added to or removed from specific regions of its DNA, thus controlling the direction of its development down one or another of the valleys in Waddington’s epigenetic landscape. What’s more, there is growing evidence that methyl marks placed on DNA during development persist and can be transferred to the next generation during reproduction, along with their phenotypic effects. Such transgenerational phenomena, though not their molecular mechanisms, have been known for decades, demonstrated experimentally in animals and observed in humans.”

As an example of an observation from the human population, Rose presents results from a wartime situation in which part of Holland was subjected to an imposed famine (referred to as the Rotterdam famine) while the remainder was not.

“During the winter of 1944 the retreating Germans imposed a blockade of food and fuel across western Holland, affecting some 4.5 million people. Children born to women who conceived or were pregnant during the famine period were found to be more susceptible to health problems such as diabetes, obesity and cardiovascular disease than their contemporaries born in the liberated eastern parts of the country. More surprising, at least to orthodox geneticists, is that similar susceptibilities have been found in their children and even their grandchildren.”

Such events are difficult to draw conclusions from because the descendents will intermarry with nonmembers of the particular population and any inherited tendencies due to the original event will be diluted.  But does that mean the effect has been erased?  Many traditional geneticists would like to believe so.

“A diminishing band of geneticists remain sceptical, arguing that unless transgenerational effects are constantly reinforced, they are gradually diluted and will eventually disappear, rather than being assimilated into the genome.”

“Epigeneticists respond with the bold claim that an epigenetic trait is, as one recent definition has it, a ‘stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence’.”

Those who consider themselves epigeneticists believe that genetics and development (nature and nurture) can no longer be considered independent fields.  Natural selection will still operate, but it must be within the context of an effectively unstable genetic basis, and it must consider environmental, social, and ecological conditions throughout the lifetime of the members of the species.  This approach is referred to as the Extended Evolutionary Synthesis (EES).

“The EES, which was presaged by Waddington, challenges the Neo-Darwinian picture of living creatures as ‘lumbering robots’, in Dawkins’s phrase, whose sole function, crushed as they are between the millstones of genes and environment, is to survive long enough to transmit the genes they carry to the next generation. Chickens, one might say, are merely an egg’s way of making more eggs.”

“In the EES, by contrast, selection operates not just on the individual adult organism but, through epigenetic processes, across the entire life cycle, and at multiple levels – genes, genomes, organisms, populations and even entire ecosystems. Co-operative interactions within and between species become important – not just competition. In the EES, as for the dialectical biologists of the 1930s, organisms do not merely accept the environment into which they are born, but work to seek out a more favourable one (the term for this is ‘niche construction’) and, having found it, they transform it, just as the beaver does by building a dam.”

The burgeoning science of epigenetics is spawning a number of research thrusts that could provide means of controlling diseases and affecting health outcomes.  Rose also warns us that it will also generate a number of commercial enterprises based on little or no science.

“Alongside the science, the pseudo-science proliferates. On the web, you can read articles claiming that mental effort can cause epigenetic change to ward off or induce cancer; advertisements sell vitamin supplements said to work through epigenetics. Practising epigeneticists try to police the boundary between science and myth while at the same time defending themselves against a residual genetic orthodoxy that continues to look on epigenetics with unease.”

One thing that should be clear to us as members of the human species is that we are not genetically and biologically inert.  Natural selection continues to work on us as we introduce new chemicals into our bodies, alter the food we eat, change our environment, vary the way we nurture our children, and even alter our mating patterns.  We are not who we were, and we are not who we will become.  And the changes may come much faster than we would have thought possible.


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