Copy Number Variation and Beneficial Mutations

In relation with this article:
Humans show big DNA differences
http://news.bbc.co.uk/2/hi/science/nature/6174510.stm


As far as I understand, variation in copy number sometimes, or often,
deternines gene-expession, or gene-function in a subtle way, and is
responsible for the small, quantitative variation beween individuals of
a population.

My issue is this:
If variations in copy-number are directly correlated with slight
variations in the phenotype, then the effects of a mutation will be
limited in scope and the chance of of a non-detrimental mutation will
be high.

To put it somewhat subjectively, because you already know what you're
going to get (a slightly longer leg bone, or whatever) this is a
relatively safe way of applying variation.

I think it's important that the following things are correlated:

variation in copy number
high------------low

variation in gene expression
high------------low (or the reverse)

variation in the concentration gradient
Steep--------------shallow

variation in morphology
Longer-------------shorter (or the reverse)

fitness
high------------low (or the reverse)


If these variables are correlated, then a mutation will result in a
small phenotypic change, causing a slight change in fitness.


The scope of a mutation is limited because:

1 Factors vary in a limited way; in one dimension (see dotted lines).

2 They are correlated. One change leads to a predictable change in the
other variables.


The chance of a non-detrimental mutation becomes high because:

1 A mutation will have virtuously the same fitness as the original
gene.
Some leg-length will do. A one millimeter longer leg will also do.
Mutations will not immediately be selected against. It is more a matter
of variation accumulating in a population, until it starts to matter.

2 In the case of directional selection, the chance of a beneficial
mutation becomes 50%.
A change in copy number (either higher or lower) will necessarily
result in a change in morphology (either longer or shorter), This will
necessarily result in a change of fitness (either higher or lower), all
in a ratio of 50%.


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