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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