Re: Haldane's dilemma

David Campbell (bivalve@isis.unc.edu)
Thu, 1 May 1997 10:00:10 -0500

>> Adrian wrote:
>> >> [most previous material sniped]
[me]
>> Much of the genome does not code for anything actually used by the cell
>> and, so far as we know, could vary freely (spacers, exons, pseudogenes,
>> etc.). Also, the estimate of harmful to neutral mutations of Kimura sounds
>> high relative to the results of mutational studies. A recent (this year)
>> Nature (sorry for the vague reference, but it's as much as I remember)
>> reviewed a paper that found most mutations had little effect on efficiency
>> of the studied proteins.
[A]
>I am sorry, but I don't get your point. If most mutations have little
>effects, then aren't they neutral?

Yes, that's my point. If most mutations are about neutral, then the rate
of mutation (as measured by comparing DNA of two species) may be quite high
and may readily explain the observed level of difference.

>> In animals, genome duplications seem to have been quite
>> rare, but gene duplication is not all that unusual. Several common genetic
>> diseases (e.g. Down's syndrome) represent duplication of sizable portions
>> to entire chromosomes; duplication on the scale of genes would rarely be
>> noticable unless it were looked for.
>
>I still don't see how this addresses the problem of getting around the
>limit imposed by cost of substitution. Perhaps you can elaborate.
>
I think these data suggest that the average cost of substitution is quite
low because of the many neutral mutations that are possible. Additionally,
many mutations have little or no physiological effect but establish
reproductive isolation. A classic example are mouse populations from
different valleys in Italy. Many of these isolated populations have unique
chromosomal rearrangements (fusion or separation) that make successful
meiosis unlikely in a cross with the normal strain.
Punctuated patterns of evolution suggest that major changes often occur
rapidly and locally, making the "average" inadequate to characterize the
whole pattern.