The Nature of Mutations II

Is the problem that people want a 1:1 correlation between
mutation and heritable variation?It seems to be a little more complex than that.

Well, surely a mutation is just an uncorrected DNA
copy error introduced during cell-division.Just because some of an organism's cells have suffered
such a copy-error doesn't mean that that will be passed on
to it's offspring ... but if it does it becomes a
heritable variation.

For me it's becuase there is a leap between DNA
sequence and gene expression.To my mind 'mutation' is one class of heritable variation,
but it appears that there are others.Mutation would then represent a low-level, data change.Presumably the gene expression control must have it's
origin in the genome (perhaps of the parent(s) ) so modifications
to this would still represent DNA sequence copy-errors ...
but an organism could inherit genes and expression patterns
separately.

Then I'd stick to my copy-errors.Ultimately the source of any kind of heritable change
must (even if from a generation or two back) be genomic
in origin (I guess).I think the important thing about 'mutations' is when
in the life cycle they occur ... it seems that some people
view it as somehow happening to the fully grown critter ...
that doesn't sound likely to me ... far too Lamarkian.

...but if it isn't in the germline then you cannot inherit it,
which is why I say mutation needs to separated from
heritable variation.With epigenetics, surely this is to do with the 'chemistry'
of the parent's cells ... and that must be related to
the parental (or grandparental, or ...) genetics at some
stage.Unless there is some chemical system operating in the cells
that has nothing to do with the DNA-mechanisms of course.

If it doesn't (even a few generations back) lead back to
a genetic source wouldn't that imply that there is some
other chemical mechanism at work within the cells that
contributes to heridity?

...true, but I think I'm safe in saying that that is
covered by a copy-error defintion of mutation.

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I'm not sure what you are getting at. Somatic DNA mutations are identical chemically to those that occur in the germline so one cannot separate mutation from heritable variation. There are heritable
and non-heritable mutations.

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That's exactly why mutation is separate from heritable variation.If you can have a non-heritable mutation ... shall I go on? I
don't think it's just semantic.

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Epigenetics is a different kind of inheritance. Inheritance of a methylation pattern would not be
detectable as a sequence difference. Take for example Dolly the cloned sheep. She was a sequence
clone, however, she had clearly not inherited a cloned copy of the methylation pattern (i.e.
epigenetic). Therefore she suffered from maladies that the original did not. Had she not been a
clone and gone through normal development, she would have inherited the proper epigenetic pattern.

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Thus, changes in either system can be considered mutation and are not simple copy errors in DNA.

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What is the origin of the methylation state in the parent?

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Also, copy error would exclude recombination, chromosomal duplication, and retrotranposition none of which are particularly associated with copy error. Downs syndrome is a disease but the extra
copy of chrosomsome 21 is not necessarily copied incorrectly.

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Why does it exclude any of the above?Do these things happen in the living cell, or when the cell
divides?For Down's syndrome, since the parents are not typically Downs
then there must have been a copy error in the germline ... the
copy error was that 2 copies of Chromosome 21 found their way
into the cell.

This thread was targetted at getting at what a mutation is
all about.It seemed to be getting confused, and over complicating the
matter.The reason, as far as I could see, was that people wanted
a 1:1 correlation between mutation and heritable change
that doesn't (necessarily) exist.If offspring can inherit both genome differences and methylation
states then both are heritable variation ... that doesn't
mean that they both have to be mutations.I suggested that a mutation (of any type) is just a DNA copy error
that goes uncorrected.Copy error because to copy means to create an identicle 'likeness'
and that doesn't happen.If we add a whole chromosome it's a copy error (two got copied
instead of one by mistake).I'm not arguing anything, and the differentiation between
a heritable change and a mutation in the sense of their not
necessarily being a 1:1 relaitonship is not semantic ... it's
simply descriptive.If not all mutations are heritable then there is not a 1:1
mapping between mutation and heritable variation.There seem to be multiple instances of heritable variations
and not all of them are mutations.What's wrong with that?

That wasn't my intent.I'm not saying that somatic mutation isn't a mutation,
I am saying that imprinting isn't.Heritable variation is any change which can be passed to
offspring. Germline mutation is one such heritable change,
there may be others.I seem to recall that your stated intent was to find an
acceptable definition for mutation that non-micro-biologists
could use to grasp the concept.At a 'system' level, when cells divide they must copy their
genetic content for the nucleus of the 'new' cell. There is nothing
vague about the term 'copy'. If the 'new' cell does not
exactly match the 'old' then there has been an error during
the copying process (like someone re-typing a whole word, or
someone hitting the wring koy on the kaybeard).It's a copy error, it happens to the DNA ... that's what I call
a mutation.If the source of the 'information' for imprinting is not the
genome, then a change in such is not a mutation ... but it
is heritable variation.

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Calling the same event in differnt cell types
mutation in one case and not the other is uncessesarily complicated.

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There seems, amongst creationists, a group that do not understand
the relationship between heritable change and mutation. They seem
to beleive that mutations happening in somatic cells are the
driving force behind evolution ... or they simply do not think
about the cells in which a mutation occurs and the organism
level impact of same.By pointing to this distinction some of said C's may at least
go 'Oh.'

If they are all directly related to genomic change, and
the only source of heritable genomic change is a germline
mutation then I don't see that we need to complicate matters
with a billion details.The only way that an offspring can differ genomically from
any possible mixing of it's parents genomes is if the successful
germ-cells suffered a DNA copy error when they formed.

For the first part, I've not (intentionally) been saying that
a somatic mutation shouldn't be a mutation only that it should
be made clear the mutations are [oops] not all there is to heritable
change.The second part was what I thought you were telling me, then I
thought it wasn't, now I KNOW it is what you are telling me What is the exact nature and origin of the 'imprinter'?Do you mean there is an enzyme for replication and another for
methylation?[This message has been edited by Peter, 07-08-2003]

So do a cell's methylation enzymes come from the 'parent'
cell or are they produced within the cell?

If the methyltransferases are passed into the 'new' cell
from the 'parent' cell (as opposed to be produced in-cell),
but were incorrectly produced within the 'parent' cell ...
I'd call that a 'protein synthesis error' (assuming it is
OK to refer to the ...ases as proteins).That would give two sources of heritable mutation ... one
in the genome (a germline mutation) and the other in the
regulatory system (a protein synthesis error).