The environment in which an embryo develops influences gene expression and some acquired traits can be inherited
BIOLOGISTS firmly believe that parents
cannot transmit to their children the
traits they acquire during their lifetimes.
Though a language can be learnt and
passed on to the younger generation,
when it comes to heritable traits, the
Darwinian theory of evolution remains
the cornerstone of existing knowledge
of evolution of life. So, if muscles are
developed by exercise, that does not
imply that the progeny is likely to grow
up to be more muscular than other children. A recent paper by Irmgard
Roemer and her team from Berlin and
Cambridge raises the startling possibility that certain acquired traits may
indeed be inherited (Current Biology, Vol 7, No 4).
The starting point of Roemer's study
was the observation that in two strains
of laboratory mice (named B and D for
short), certain nuclear transplantation
experiments between the strains were
causing alterations in patterns of gene
expression. Three factors play a role in
this. First, the genome of the developing
embryo, which is surrounded by an
internal environment, the cytoplasm,
derived from its mother. Second, the
genetic material derived from the mother via the nucleus of the egg. Andfinally,
an equal complement of genetic material coming from the nucleus of the
When specimens from either of the
strains B and D are bred within the
strain, the resulting embryo can be
denoted by the symbols BBB or DDD, in
accordance with the three factors of
maternal cytoplasmic environment,
maternal genes, and paternal genes. A
hybrid formed by mating a B mother
with a D father would be BBD, while one
derived from a D mother and B father
would be DDB, as two of the three influencing factors come from the mother.
In all these cases, as also in other conventional crosses between a hybrid and
either parental type, the pattern of proteins synthesised by the embryo is what
one might term normal.
In striking contrast, two proteins are
strongly repressed in both BDB and DBD
hybrids. These are artificially generated
embryos and can never occur in nature.
For example, BDB implies that a D-type
female nucleus is surrounded, not by its
own cytoplasm as is normally the case,
but by B-type cytoplasm. In order to
generate such a 'nucleocytoplasmic,
hybrid, the nucleus from a D egg has to
be removed and transplanted into a B
egg, after the removal of its own nucleus.
Curiously, the two proteins with
depressed levels of expression in BDB
and DBD hybrids have interrelated functions. One belongs to the class of major
urinary proteins (mup) and the other is
an olfactory marker protein (Omp). omp
is expressed in the mucosal layer in the
nose and transported to the olfactory
bulb at the front of the brain. There, in
combination with molecules such as
mup, it is involved in 'presenting'
pheromones, or sexual attractants, to
What this goes to show is that early
environmental influences - in this case
the environment provided by the cytoplasm of the egg - can have long-lasting implications on gene expression.
Also, given the nature of the affected
proteins, the effect appears to extend to
adult behaviour (though this has not been tested).
What was more important was that
the altered patterns of gene expression
found in nucleocytoplasmic (NC)
hybrids continued into the next generation. This was true even when an NC
hybrid male was crossed with a B or D-type female. The significance of this lies
in that the cytoplasm of the newly fertilised embryo, which contains some
genetic information within structures
called mitochondria, is derived almost
entirely from the mother. However, the
only genes that an Nc hybrid male can
pass on are those that are contained in
its nucleus. Therefore if an Nc hybrid
male can transmit changed patterns of
gene expression, it signifies that a characteristic acquired early in life was successfully passed down in a hereditary fashion.
The researchers have suggested an
explanation that accords with modern
Darwinian theory. It was observed that
in all cases in which an animal showed a
reduction in the level of expression of
the mup protein, there was a concomitant change in the mup gene: it had an
increased number of methyl groups
attached to the DNA.
Studies of many systems over a
number of years have shown that, firstly, methylation Of DNA can affect the
level of expression of the protein encoded in that molecule. Secondly, the level
of methylation, which can be influenced
by external cues, can also persist over
generations. In other words, a changed
pattern of gene expression can occur,
not only because of a mutational change
in the conventional sense, but because
of a reversible chemical modification
(in this case, methylation) of the DNA.
And if the modification does not revert
in the immediately succeeding generation, the change can persist. Indeed, '
there is an example in which methylation increases stepwise from one gener,
ation to the next, and leads to a steady
generational increase in the severity of
the effects it causes.
The results indicate that the
environment within which early embryonic development takes place could
have long-term, transgenerational
effects. This should make scientists
wary of assuming that in vivo fertilisation or embryo cloning will have
no long-term effects. The findings
support the belief that even seemingly
mundane causes have the potential to
harm future generations.
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