Why should physiologists be concerned about these questions?
A major problem with
the modern synthesis from the viewpoint of physiology is
that it excludes phenotypic function from having any role
whatsoever in influencing the direction and frequency of
genomic change. This is what neo-darwinists really mean when
they refer to gene changes as ‘random’. It doesn’t really
matter to them whether the changes are ‘truly’ random. What
matters is whether function can influence those changes.
Through that crack, if it exists, will flow all that they
wish to exclude, including strong forms of the inheritance
of acquired characteristics. If the modern synthesis is
correct, then physiology really is dealing with the
disposable carrier of genes. If however, on this central
point, it is incorrect then, as I say in the article “It is
hard to think of a more fundamental change for physiology
and for the conceptual foundations of biology in general”.
That, incidentally, is the justification for the title of
the article. I did not choose the title light-heartedly.
PLEASE NOTE
that the answer to this very important question is
necessarily very technical. But I think it is necessary to
give the full details. The angel in this case lies in the
detail. The devil will lie with those who are unprepared to
study the detail but who still wish to claim that the ‘earth
has not moved’.
The key to this
question lies in four major discoveries:
First,
some of the non-random changes in the genome are
functionally significant.
“Changes in the speed of change
are well known already from the way in which genome change
occurs in immunological processes. The germ line has only a
finite amount of DNA. In order to react to many different
antigens, lymphocytes ‘evolve’ quickly to generate extensive
antigen-binding variability. There can be as many as 1012
different antibody specificities in the mammalian immune
system, and the detailed mechanisms for achieving this have
been known for many years. The mechanism is directed,
because the binding of the antigen to the antibody itself
activates the proliferation process. Antigen activation of
B-cell proliferation acts as a selective force.”
This example was
given first because targeted genome change in the immune
system is well-documented and has been known for a long
time. That it can happen in B-cells as they ‘evolve’ to
generate the variability shows that the mechanism of such
targeted genome change is not new. We should not therefore
be surprised to find that it is used elsewhere in the
organism. Now let’s move to the part of the article that
deals with evidence beyond the immune system.
“Similar targeted
genomic changes occur outside the context of the immune
system. The reader is referred to table II.7 (Shapiro, 2011,
pp. 70–74;
http://shapiro.bsd.uchicago.edu/TableII.7.shtml)
for many examples of the stimuli that have been shown to
activate this kind of ‘natural’ genetic engineering, while
table II.11 from the same book
documents the regions of the genomes targeted. (pp.
84–86;
http://shapiro.bsd.uchicago.edu/TableII.11.shtml).
Thirty-two examples are given. One example will suffice to
illustrate this. P element homing in fruit flies involves DNA
transposons that insert into the genome in a functionally
significant way, according to the added DNA. There is up to
50% greater insertion into regions of the genome that are
related functionally to DNA segments included within the P
element. Thus, ‘Insertion of a binding sequence for the
transcriptional regulator Engrailed targets a large fraction
of insertions to chromosomal regions where Engrailed is
known to function.’ (Shapiro, 2011, p. 83)”
Second,
some forms of non-DNA (epigenetic) inheritance have been
shown to be as robust as DNA inheritance and to be
transmitted for many generations.
The details on this
point are given in the answer to the
question how widespread non-DNA inheritance is.
Bard JBL (2008). Waddington’s legacy to developmental and
theoretical biology.
Biological Theory
3, 188–197.
http://www.deepdyve.com/lp/mit-press/waddington-s-legacy-to-developmental-and-theoretical-biology-o0mS0JjRau
Waddington showed a
form of inheritance of an acquired characteristic that was
initially ‘soft’ in the sense that it required repetition of
the environmental stimulus in each generation to maintain
it. But after about 14 generations it became ‘hard’, i.e.
assimilated into the genome. I think that what was happening
was that the separate alleles necessary for the
characteristic were already present in the population but
not in the right combination to be expressed without the
stimulus. The environmental stimulus was eventually not
needed because by that generation the correct combination of
alleles was now present in individuals who could pass this
pattern of alleles on to the next generation in the standard
genetic way. I summarise this point in the article by
writing “After all, the pattern of the genome is as much
inherited as its individual components, and those patterns
can be determined by the environment.”
“Epigenetic effects can even be
transmitted independently of the germ line. Weaver and
co-workers showed this phenomenon in rat colonies, where
stroking and licking behaviour by adults towards their young
results in epigenetic marking of the relevant genes in the
hippocampus that predispose the young to showing the same
behaviour when they become adults
(Weaver et al. 2004; Weaver, 2009).”
Weaver ICG, Cervoni N, Champagne FA, D’Alessio AC, Sharma S,
Seckl JR, Dymov S, Szyf M & Meaney MJ (2004). Epigenetic
programming by maternal behavior.
Nat Neurosci 7, 847–854
http://www.ncbi.nlm.nih.gov/pubmed/15220929
Weaver ICG (2009). Life at the interface between a dynamic
environment and a fixed
genome. In Mammalian Brain Development. ed. Janigro D, pp. 17–40. Humana Press,
Springer, New York, NY, USA.
Neo-darwinists tend
to dismiss this kind of example as a form of cultural
inheritance. So it is. But it works by marking the genome of
the next generation. It is therefore just as relevant as and
just as robust as epigenetic inheritance in general. Rats
and other rodents do it all the time.
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The MUSIC of Life: Biology Beyond the Genome ©Denis Noble |