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Archiver > GENEALOGY-DNA > 2005-01 > 1105872797


From: Gordon Hamilton <>
Subject: Re: [DNA] Male Line Specific Y-STR Average Mutation Rates
Date: Sun, 16 Jan 2005 05:53:26 -0500
In-Reply-To: <200501151733.j0FHXSjV019097@lists5.rootsweb.com>


I have been following this discussion between Charles and the rest of the
group with some interest and thought I would weigh in with some thoughts
from a somewhat different perspective. I am not a statistician but I do
understand what John and Ann and others are saying if the process is
completely random. However, I have to come down on Charles' side in this
discussion because, on the basis of my background in enzymology and
biological chemistry, I can well imagine a mechanism whereby different
families could have different rates of STR mutations. In fact it is very
possible, even probable, that the rate of mutation would be influenced by
the mother in many transmission events.

The replication of DNA requires catalysis by enzymes and it is well
documented that the same enzyme in different individuals may not have
exactly the same structure and catalytic properties. Very often specific
enzymes (proteins) differ by one or more amino acid substitutions. Since
such differences are inherent in the genes, they are either passed on from
generation to generation or they prove fatal to the organism. If the
substitution leads to a protein that is catalytically inactive as an enzyme
(or nearly so), it is usually fatal or leads to a serious genetic disease
in some of the offspring. We are not concerned with such serious situations
here. Rather, I would like to focus on cases where the amino acid
difference causes a more subtle change in the characteristics of the
enzyme; the enzyme is still catalytically active but its properties are
slightly altered depending on which amino acid is present in the enzyme. In
such cases it seems very possible that one of the properties altered by an
amino acid difference would be the fidelity with which an enzyme catalyzes
the replication of the DNA or how efficiently a repair system corrects any
mistakes in the replication. This overall process involves several enzymes
so there are several possibilities for one or more of the enzymes in the
process to be modified from one individual to another. Thus, it seems to me
very possible, almost predictable, that the rate of STR mutations would be
individual (or family) specific and not the same for everyone.

It is not clear to me exactly when the STR mutation, that is ultimately
passed down through generations, initially manifests itself in the
fertilization process and development of the fetus. However, I suspect that
the enzymes involved in the DNA replication process that leads to the STR
mutation could come from the father or mother or a genetic mix of the two.
Therefore, it seems likely that the probability of an STR mutation in any
specific transmission event could be influenced by the mother's genes as
well as those of the father. In this regard, I wonder whether there is any
evidence for differing STR mutation rates in the offspring of fathers who
have had two or more wives. I suspect it will be quite a while before we
have enough data to be able to satisfy the statisticians among us that any
such difference is due to anything other than chance. In any event,
Charles' new log is a start.

Gordon Hamilton

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