Re: Darwin and Lamarck

Chris Lees (
Mon, 26 Apr 1999 01:12:04 +0100

Date: Mon, 26 Apr 1999 01:12:04 +0100
From: Chris Lees <>
Subject: Re: Darwin and Lamarck

and this is part the second.

> But the real bombshell was yet to come. MUP proteins are usually secreted in
> mouse urine and, along with pheromones, are signalling chemicals vital to
> normal sexual behaviour in mice. OMP, on the other hand, is part of the
> olfactory system that allows mice to recognise pheromones. Not surprisingly,
> when the smaller mice grew up they were slow to mate. When they did mate
> eventually, Reik and his colleagues Irmgard Roemer, Wendy Dean and joachim
> Klose were amazed to discover that not only were the offspring smaller than
> usual, but that the MUP and OMP genes were again methylated and switched
> off. The epigenetic changes had passed down from one generation to the next.
> Once you accept that epigenetic inheritance occurs, it's far easier to
> envisage how drugs, hormones and starvation could have created the bizarre
> transgenerational effects in rodents and perhaps even in humans, says Reik:
> the chemicals and the diet may have triggered the heritable methylation of
> certain genes. At first, however, "we tried very hard to disbelieve our
> results", says Reik. But as they checked and double-checked their data, and
> studied the literature, things just fell into place. It turned out that
> there had been a smattering of earlier reports of mice inheriting epigenetic
> changes. Ten years ago, Christine Pourcel at the Pasteur Institute in Paris
> discovered that when a gene from a virus was inserted into mice it became
> methylated and silenced, and that the modification was passed on to the
> offspring. And in 1990, Azim Surani and his team at the Wellcome Trust and
> Cancer Research Campaign Institute of Cancer and Developmental Biology in
> Cambridge found other cases of epigenetic inheritance when genes were
> shifted from vir-uses into mice. Those earlier transgenic experiments were
> generally deemed too artificial to be of any consequence in the natural
> world. Not so Reik's mice, it seems. "It's lovely work," says Lawrence
> Hurst, an evolutionary geneticist at the University of Bath. Transferring a
> nucleus from one mouse egg to another is undoubtedly an unnatural thing to
> do, but as Reik points out, the procedure could mimic changes that happen
> naturally. In of development, the activity of genes is in tremendous flux,
> being turned up and down as methyl groups and proteins are added and
> removed. Similarly, as the nucleus is moved from one egg to another in
> Reik's experiment, it experiences differences in temperature and
> concentrations of various chemicals, all of which could permanently change
> the methylation of certain genes. Curiously, cloned lambs and calves created
> by nuclear transfer-a technique similar to the one used to create Reik's
> undersized mice-may be up to twice as large as normal. No one knows what
> causes the phenomenon, whether genes are "inappropriately" methylated or
> whether the oversized offspring, if bred, would pass the trait on. "But our
> observations raise the question of whether or not such manipulations could
> actually have a long-term impact by being transmitted to future
> generations," says Reik.
> And if physical manipulations of embryos is all it takes to trigger
> inappropriate methylation of some genes, then that may be a good reason to
> worry about what happens to human sperm, eggs and embryos during high-tech
> fertility treatments. All three are routinely squirted through pipettes,
> swirled around in lab dishes, or frozen during procedures such as in vitro
> fertilisation or genetic testing of embryos. What's more, there have been
> some reports-albeit controversial-that babies born following IVF are smaller
> than normal (see "Shots in the dark for infertility", New Scientist, 27
> November 1993, p 13). Reik's mice also highlight another potentially
> worrying issue. Hurst, and developmental biologists such as Martin Johnson
> of the University of Cambridge, argue that in an effort to sell the genome
> sequencing projects to the public and the funding agencies, molecular
> biologists have created the misleading impression that genes alone run the
> show. The constant emphasis on the power of genes, he says, has created "a
> 20th-century form of fatalistic predestination", in which people believe
> they are the product of their genes, nothing more, nothing less. Even
> geneticists, he says, have lost sight of the huge range of environmental
> factors that can change a gene's activity, ranging from an adult's diet to
> certain high-tech fertility treatments. For those reasons, some geneticists
> are calling for a new definition of the gene, based on not only its DNA
> sequence, but also its epigenetic instruction manual-the degree of
> methylation, for example. But can epigenetic alterations, heritable or
> otherwise, really be worth the fuss? Yes, according to Eva jablonka, an
> evolutionary biologist at Tel-Aviv University. In her book with Marion Lamb,
> Epigenetic Inheritance and Evolution, The Lamarckian Dimension, she points
> out that the idea that the effect of the environment on one generation's
> epigenetic instruction manual can be passed to the next is old hat to
> students of simpler organisms like bacteria, yeast, plants, and even fruit
> flies. For example, in yeast, the epigenetic silencing of one of two genes
> produces changes in sex that are inherited. And just a few months ago,
> Renato Paro of the Centre for Molecular Biology in Heidelberg, Germany,
> reported a striking example of epigenetic inheritance in laboratory fruit
> flies (Cell, vol 93, p 505). The activity-but not the sequence-of a key gene
> was changed in embryos that went through a brief heat shock, activating
> another gene that caused the flies to have red eyes, a trait they passed on
> to their offspring. jablonka theorises that epigenetic inheritance in lower
> organisms at the very least play a key role in evolution by providing an
> additional source of variation on which selective pressures can act.
> Although epigenetic changes may be as random as mutations in the DNA
> sequence, they could also be adaptive, triggered by environmental changes to
> enable simple organisms to respond quickly to a fluctuating environment. For
> example, if one source of bacterial food is in short supply, heritable
> epigenetic modifications could help populations of bacteria to switch to
> another food source. Jablonka also points out that epigenetic inheritance is
> not at odds with classic inheritance via the genes. Instead, it would be a
> complementary inheritance system, with Darwin's natural selection acting on
> both the modified gene and on the genes that control epigenetic
> modifications. Meanwhile, Pembrey, provocatively calling himself a
> "neo-Lamarckian", is prepared to stick his neck out even further, and
> suggest an adaptive role for epigenetic inheritance in higher organisms such
> as humans. He speculates that the inheritance of epigenetic factors which
> control a few select genes may have enabled human populations to regulate
> the growth of individuals according to food availability. Food shortages
> could generate physiological responses in adults, say, a change in hormone
> levels, that influence the activity of key growth genes. This could then be
> passed on to their offspring by varying the genes' methylation. In the short
> term, such an adaptive mechanism could, for example, ensure that the baby's
> head is not too big for the mother's birth canal. In the longer term, if the
> offspring also passed those epigenetic changes on to their offspring, it
> would result in generations of progressively smaller people, until a period
> of plenty created the epigenetic changes that reversed the trend. The two
> generations of small babies that followed the Dutch famine could be
> explained by just such epigenetic adaptation, says Pembrey Perhaps, he says,
> the giants of Patagonia (literally "the place of big feet") reported by
> Ferdinand Magellan in the 16th century and countless later European
> travellers, really did exist. "What we can see now is the tip of the
> iceberg," says Marilyn Monk, a molecular embryologist and geneticist and a
> colleague of Pembrey's at the Institute of Child Health in London. She
> predicts that many more examples of epigenetic inheritance in mammals will
> come to light once geneticists develop ways to monitor methylation across
> the entire genome during an embryo's development. What's more, she says, the
> much-cherished notion that sperm and egg genes are totally sheltered in the
> ovaries and testes starts to look shaky when you examine it more closely: in
> humans, the primordial cells that generate eggs and sperm are busy dividing
> up until the 15th week of development. Not everyone is prepared to take such
> radical positions as those of Lamb and Pembury. John Maynard Smith, an
> evolutionary biologist at the University of Sussex, remains sceptical. He
> points out that even if epigenetic modifications occur naturally in mammals
> and are passed down the generations, there is still no reason to suspect
> that they are any more "adaptive" than random gene mutations that are passed
> on to offspring. Reik, too, cautions against overinterpreting his results.
> "Whether any such epimutations have any adaptive significance remains to be
> established," he says. No one has yet shown that inherited epigenetic
> changes occur naturally in mammals, and even if they did they may still be
> rare, random and inconsequential events-even downright dangerous. Whatever
> the final verdict on the significance of epigenetic changes, one thing is
> already clear, says Hurst: "Epigenetics matters." As the human genome
> project rushes to completion, the really interesting insights are going to
> come not from the sequences, he predicts, but "from working out how genes
> are controlled".
> Further reading: Epigenetic Inheritance and Evolution, The Lamarckian
> Dimension by Eva Jablonka and Marion Lamb (Oxford University Press, 1995)
> Genomic Imprinting, edited by Wolf Reik and Azim Surani (Oxtord University
> Press, 1997) "Epigenetic programming of differenbal gene expression in
> development and evolution" by Madlyn Monk, Developmental Genetics, vol 17, p
> 188 (1995) "Epigenetic inheritance in the mouse" by lrmgard Roemer and
> others, Current Biology, vol 7, p 277 (1997) "Imprinting and
> transgenerafional modulabon of gene expression: human growth as a model" by
> Marcus Pembrey Acta Genet Med Gemmeliol, vol 45, p 111 (1 996)
> "Transgenerational effects of drugs and hormone treatment in mammals: a
> review of observations and ideas" by J. Campbell and R Perkins, Progress in
> Brain Research, vol 73, p 535 (1988)

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