From: smt1179@ritvax.isc.rit.edu (Tom Thatcher)
Subject: Re: Genetic clock
Reply-To: smt1179@ritvax.isc.rit.edu
Organization: Rochester Institute of Technology
Date: Thu, 15 Oct 1992 02:16:28 GMT

In article <1992Oct12.125736.26481@hsr.no>, onar@hsr.no (Onar Aam) writes:
>    In genetic evolutionary biology one often talks about the genetic clock, a
>dating technique which uses the difference in various genomes to estimate the
>time of divergence. A controversal aspect of the genetic clock is that the
>originators of the technique assume that the divergence is constant through time. 
>Many argue that evolution is not a linear process and hence divergence should not
>be constant. I have come up with a theory which supports constant divergence. I
>do not know whether this is already known. If so I would like to hear about it.
>    In most 'higher' species there vast amounts of junk DNA, sequences which have
>no distinct impact on the specie. These sequences are not retained by selection
>preassure, and therefore they will gradually erode.

Junk DNA is not junk just because you don't know what it does.  The fact that
it is kept around strongly suggests that it is very good at at least *one*
function; keeping itself around.  

> If we regard mutation rate as
>constant, we can assume that the junk DNA erodes at a constant pace.

DNA does not erode, like a mountain.  It simply changes sequence letters.


The assumption that DNA mutates at a constant rate is just as shaky with
regard to "junk" DNA as it is to functional DNA.  For one thing, generation
times have changed dramatically over the eons.  Since the only DNA whose
mutation can be inherited is the germline DNA, mutations can only be passed
on once per sexual generation.  This was perhaps daily to weekly in the case
of microbes and small eukaryotes, then monthly to yearly for early plants and
small animals, to once every two decades for modern humans.

 Since the
>amount of junk DNA is much, much larger than the amount of functional DNA, we
>need not take the functional DNA into account. This means that the genetic clock
>is an approximately linear function of time with a possible 5% inaccuracy. This 
>will initially only work on comparisons of whole genomes (or large strings of DNA)


You toss that off with remarkably little attention.  To verify that so-called
junk DNA changes at a constant rate, large quantities will have to be sequenced
from many organisms; not a trivial task.

More critically, DNA and proteins are used as clocks since we can be reasonably
sure that cytochrome c, for example, in humans and bacteria are distantly
related, because they have sequence similarity and perform identical functions.
If the so-called junk DNA has changed too much, how will you tell which
piece of human "junk" DNA matches a certain piece of mouse "junk" for
example.

Since DNA does not erode, only changes letters, there is no way to predict
what a sequence originally looked like unless you have many similar sequences
from many organisms which you can reasonably say are related.


>I will try to show that this is true also for the protein test, comparison of
>proteins. 
>    As we know, proteins reflects functional genes. Thus, we cannot rely on the 
>steady decay of junk DNA since they do not affect the proteins. On the other hand
>we know that many sequences are equivalent. It doesn't matter which is which.
>They code the same acids. This also means that they are not a subject to
>selective preassure and therefore the same conditions exist for these sequences
>as for junk DNA. If species no longer interact (sexually) these sequences will
>diverge. And because they are only a subject to mutations, which is constant,
>they will diverge linearly. Hence linearity also applies to the proteins although
>the uncertainty will be greater than in direct genome comparison.

As far as DNA codes for proteins are concerned:  Even though some amino acids
can be encoded by several DNA sequences (synonomous codons) some organisms use
a highly restricted set of codons and never use others.  This implies that there
is a reason for this.  Your suggestion relies on codon use being random,
which it is not.

Proteins are the unit of selection for DNA that codes for proteins.  Evolution
acts on the DNA only through proteins.  If a DNA change causes a protein 
change that is bad, the DNA is lost with the organism in question.


On the subject of molecular clocks in general:

The problem is not as great as it appears.  There is probably no single 
molecule, DNA, RNA, or protein, that is an accurate, constant clock.  
But, by examining many molecules of different types, the clocks that appear
will converge on some central value, some central picture of evolution
(just like if you flip a coin a few times, you are likely not to have
a 50% value for heads, but as you flip more and more, the value converges
on 50%.)
>

I have myself constructed 6 evolutionary trees using 6 different proteins
as molecular clocks and although the trees were not identical, there were
many large scale similarities and most of the differences were in the
small details.

   
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^ Q:  "What must I do to convince you people?"  ^  Tom Thatcher
^ WORF:   "Die."                                ^  University of Rochester
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