Re: rapid variation

Walter ReMine (wjremine@mmm.com)
Fri, 08 Sep 1995 12:37:10 -0500

Abstract: Glenn Morton has continued with his vague, ill-formed, and in the
end, false, argument that humans cannot rapidly originate genetic variation.

Glenn writes:
>The rate was 1e-7 per nucleotide location per generation. This
>means that any given location in your genome has a 1e-7 chance of having a
>nucleotide that your parents didn't have. Thus when you multiply this by the
>3.5 billion nucleotides in the human genome,

Small correction. That genome size is for the human HAPLOID genome, that
is, it is the size of the genome carried by a human sperm (or an
unfertilized egg). The human offspring is diploid and receives mutations
from both the sperm and egg, thus doubling the mutation rate experienced by
offspring. Thus, by Glenn's own figures, each human progeny receives 2 x
3.5e9 x 1e-7 = 700 new mutations.

******

By Glenn's own figures, a gene 1000 nucleotides long would have (1000 x
1e-7) one chance in 10000 of receiving a mutation. When Glenn applied that
figure he again forgot that humans are diploid:

>You have 1000 x 1e-7 = 1e-4 which is the odds that in the generation that
>created you, you will have a mutation in a given protein.

Small correction. Since humans are diploid and contain two copies of each
gene, the mutation rate per progeny for that gene is TWO in 10000 (not one
in 10000, as Glenn calculated).

******

>I do not know how common the alleles are in the population but that is not
>relevant to the problem at all.

On the contrary, allele frequency is relevant to the genetic variation
problem. Let me show why.

Glenn says the issue is the number of alleles PRESENT in the population. He
claims that humans cannot go from 10 alleles to 59 in 200 generations. I
showed in previous posts that it can easily happen in merely ONE generation.
For simplicity sake, imagine a population of one million adults containing
only ONE version of a gene, all identical. There is only ONE allele, by
definition. Since the population is diploid there are two million copies of
the gene in the population. In one generation that gene suffers mutations at
the rate of 1 per 10000 (that's Glenn's figure). Thus, there would be 2e6
/ 10000 = 200 new mutations to that gene in merely one generation. That's
200 new alleles PRESENT in the population in merely ONE GENERATION. Glenn's
argument is flatly wrong.

That is why Glenn keeps shifting his argument. And when he shifts his
argument, the allele FREQUENCY is no longer an irrelevant issue. It becomes
a central issue. Yet no where does Glenn discuss it. That is why his
argument is ill-formed. As I pointed out in previous posts, there are many
ways to define genetic variation, and Glenn never picks one and sticks to it
long enough to make an argument.

******

>Let me illustrate two alleles, using letters in
> place of nucleotides.
>
>allele 1
>
>abbdcbdabcdbabdbad
>
>allele 2
>aabbabdabccbabdcdd
>
>If I counted correctly there are 6 differences between these two very short
>alleles. If the logic of the situation requires that allele 2 be derived by
>random substitution from allele 1 then what you have is one of those puzzles
>I can never do, in which you are asked to go from the word "wore" to "bass" by
>making a one letter substitution at each step always having a real word at
>each step. In other words you can't have "wors" because that is not a word.
>
>wore-ware-wart-dart-dare-bare-bars-bass
>
>This is how allele 2 must be derived from allele 1. If a substitution gives a
>"non-word" like "wors", e.g. a harmful gene, then the guy dies without leaving
>offspring.
>
>We know the probability of a substituion at each location each generation, so
>it is mere probability to look at allele 1 and tell how long (on average) it
>must have taken to derive allele 2. With six substitutions, the odds are that
>it took 60,000 generations to make the six substituions. Since human
>generations are 20 years or so, then 20 x 60,000 = 1,200,000 years.

Glenn speaks of "six substitutions". WHAT six substitutions? He never
showed ANY DATA on humans showing that modern alleles typically differ by
six nucleotides. The data he offered (the "59 alleles of MHC genes") lacks
this necessary information. Glenn ASSUMED (out of thin air) that SIX
substitutions are necessary. He is wrong for doing that. That data for
typical genes shows no such thing.

In addition, Glenn totally overlooked the possibility that the 10 alleles
possessed by the original population may have ALREADY differed at many
nucleotide positions. Once again, Glenn's argument is ill-formed.

In addition, Glenn model of the how genetic variation accummulates in a
population is wrong. He modeled the process as though it were ONE copy of a
gene IN THE ENTIRE POPULATION, as though it were a haploid organism with a
population size of ONE. That is flatly wrong. It does not correctly model
the way human populations accumulate genetic variation. A) Humans are
diploid. B) Human populations have been in the millions for most (if not
all) recorded history. Those two factors were left out of Glenn's model.

Thus, Glenn failed on all three legs of his argument. 1) He failed to
understand the genetic variation that could have plausibly been present in
the original population. 2) He failed to understand (and document) the
genetic variation that is typical of genes today. 3) He incorrectly
modeled the process whereby genetic variation is accumulated.

******

I also point out (once again) that Glenn SELECTED the MHC genes because they
have the highest number of alleles. In other words, he SELECTED those
particular genes that most favored his point of view. But MHC genes are
distinctly UNTYPICAL, they do not represent typical genes. As Steve Clark
pointed out, MHC genes -- UNLIKE MOST ALL OTHER GENES -- are subject to gene
conversion, which injects genetic variation into those genes at a much
higher rate. Glenn's assumptions about the mutation process and its rate of
occurrence DO NOT APPLY TO THE MHC GENES.

Sorry for the shouting, but virtually everything I am saying in this post
Glenn has already heard before. Yet he continues with the same ill-formed
and false arguments. Most loci of present-day animals contain between 1 and
5 alleles (Mani 1984, p. 282), so Glenn's selective use of the MHC genes is
fallacious on several grounds.

******

Glenn has not shown the slightest implausibility in the rapid origin of
genetic variation.

Walter ReMine
P.O. Box 28006
Saint Paul, MN 55128