On Tue, 1 Jun 2004 15:25:44 +0000 (UTC),
Tim Tyler said:Larry Moran <[email hidden]> wrote
or quoted:
Quoted message said:The question you didn't ask is what percentage of
mutations have selection coefficients that are large
enough to ensure fixation in reasonable-sized
populations.
In my example, the mutants were *deleterious*. Selection
prevented their fixation by genetic drift. The alleles
weren't fixed by selection - they were prevented (by
selection) from reaching fixation (by genetic drift).
In other words, the other, beneficial, allele was selected
over the deleterious allele.
Quoted message said:The question of how many mutations are sufficiently
deleterious to be affected in this way in realistic
populations is an interesting one
- but some are bound to be, and that seems sufficient to
establish that the chance of alleles getting fixed by
genetic drift can be a function of the size of the
population.
The probability of a *particular* allele becoming fixed by
random genetic drift (alone) is 1 P = --- 2N
where N is the population size. This means that the
probability for each allele depends on the population size.
This isn't disputed. The probability of *any* allele
becoming fixed in a population by drift is the probability
of fixing each allele times the number of alleles that arise
by mutation. The number of alleles that arise in a
population is given by 2Nu where u is the rate of mutation
(per gene per generation).
Thus, the rate of substitution of neutral alleles in a
population is
1 K = 2Nu x --- = u 2N
and it is independant of population size.
For beneficial alleles that arise in a population the
probability of fixation can be approximated by
P = 2s
where s is the selective advantage. This equation holds for
small values of
s (s< .05) and populations greater than about 100
individuals. It is pretty much independant of
population size for realistic populations. For a
population of 100 and a selective advantage of 0.001
the equation yields a probability of 0.002 (0.2%) and
this is only a bit higher than the probability (1/2N =
0.005) that the allele would be fixed by drift alone it
it were neutral. As the selective advantage goes even
lower (i.e. very close to neutral) the probability of
fixation by natural selection falls below the
probabilty of fixation by drift.
Your simulations were a bit unrealistic since you started
with equal numbers of deleterious and benefical alleles
(50:50) and very small populations. You didn't explain how a
deleterious mutation rose to the level of 50% in your
populations.
Quoted message said:Quoted message said:You also need to ask whether there's any evidence that
the nucleotide substitutions we see in most DNA could
possibly be slightly advantageous or slightly
deleterious.
Nucleotide substitutions that seem close to neutrality can
nontheless have effects on the phenotype in several ways.
For example, substitutions in junk DNA can be expressed by
removing stop codons.
Similarly, "third-base" mutations can have effects even if
they result in the same amino acid being coded for - since
they can alter the probabilities of the sequence mutating
into the sequences representing other amino acids.
Some viruses use enzymes to target particular DNA
sequences - to identify where to paste themselves. While
such enzymes exist the exact details of the DNA sequence
are likely to have selective consequences.
In other words, neutrality is an ideal which is not
realised in practice - practically all alleles have some
non-zero selection coefficient associated with them.
All of these hypothetical examples are situations where a
neutral allele isn't a neutral allele. You'll get no
argument from me on this point. There certainly are alleles
that have low selective advantages and are affected by
natural selection in competition with random genetic drift.
On the other hand, there are lots of mutations in junk DNA
that aren't likely to have any effect on the organism. I
conclude that that there are thousand and thousands of truly
neutral alleles that have become fixed in the human
population over time.
We began this discussion when I said that random genetic
drift is the main mechanism of evolution when you take into
account *all* of evolution. So far you haven't given me any
definition of *all of evolution* that causes me to change my
mind. Right now you seem to be trying to deny that there are
any such thing as neutral mutations - even in junk DNA. Is
that how you intend to continue the discussion? Are you
saying that random genetic drift isn't the main mechanism of
evolution because (almost) all mutations are either
beneficial or deleterious?
Larry Moran
