mutant recessives

Robin Panza panzar at CLPGH.ORG
Sun May 11 11:24:31 CDT 1997

>I do hate to be this stupid, but why would having two nonidentical, recessive
>alleles (that is, ones that code for nonfunctional proteins) be any different
>than having two identical recessive alleles? In a double recessive, a

When a mutation occurs, it often (but *not* always) results in non-functional
protein product.  Other possibilities are that there is no change (mutation to
a redundant codon that results in the same amino acid at that site), that the
change is functionally neutral (mutation at a site that doesn't noticeably
alter protein configuration/function), or change that alters, but does not
destroy protein function (may increase or decrease enzyme activity or slightly
alter structures built with that protein, either of which may be beneficial,
harmful, or neutral).

As for mutations to non-functionality, there is a difference between
pseudohomozygosity  (PZ) and true homozygosity (HZ).  Both PZ and HZ expose
the alleles to selection.  However, PZ alleles are essentially in competition.
The two alleles can be thought of as "cooperating" when they are at very low
frequencies, as they are more likely to be expressed as PZ than HZ. Remember
Hardy-Weinberg? The frequency of HZ is q2, while the frequency of PZ is
2pq>q2.  At higher frequencies of the mutants (having increased by whatever
combination of selection and drift), we have to switch to the 3-allele version
of H-W, where p=original allele and q and r are the mutants.  Then equilibrium
is described by    p2 + 2pr + 2qr  +  q2 + 2qr + r2
                   dom. phenotype     rec. phenotypes
The mutants are starting to show up as HZ.  Any frequency difference between
q and r will result in different rate of expression of the mutant (HZ)
phenotypes, and any increase in q must be at the expense of p *and* r.  q and r
are selectively neutral relative to each other, and their selective advantage
is the same relative to p.  Changes between q and r are affected only by drift,
which can be significant while they are uncommon.  Different frequencies will
result in different frequencies of the two recessive HZs, which will affect the
relative selective force.

>brings me back to my original question: In a classical system, how do we know
>that two recessive alleles are identical if any number of possible mutations
>may produce nonfunctional proteins which would have the same effect

This part is easy to answer--by DNA sequencing.  The difference in sequence
will expose the PZ.  The only vague area is whether two identical sequences
are truly homologous (decendents of the same original mutation event, rather
than the same mutation having occured twice in the past).  Granted, the latter
should be very rare, and so identical DNA sequences are assumed (via Occam's
Razor) to be from the same mutation history.

Robin K Panza                   panzar at
Section of Birds, Carnegie MNH
Pittsburgh  PA  15213  USA

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